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CHEMISTRY (598 journals)                  1 2 3 | Last

Showing 1 - 200 of 735 Journals sorted alphabetically
2D Materials     Hybrid Journal   (Followers: 8)
Accreditation and Quality Assurance: Journal for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 26)
ACS Catalysis     Full-text available via subscription   (Followers: 32)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 17)
ACS Combinatorial Science     Full-text available via subscription   (Followers: 23)
ACS Macro Letters     Full-text available via subscription   (Followers: 23)
ACS Medicinal Chemistry Letters     Full-text available via subscription   (Followers: 39)
ACS Nano     Full-text available via subscription   (Followers: 227)
ACS Photonics     Full-text available via subscription   (Followers: 11)
ACS Synthetic Biology     Full-text available via subscription   (Followers: 21)
Acta Chemica Iasi     Open Access   (Followers: 2)
Acta Chimica Sinica     Full-text available via subscription   (Followers: 1)
Acta Chimica Slovaca     Open Access   (Followers: 1)
Acta Chromatographica     Full-text available via subscription   (Followers: 9)
Acta Facultatis Medicae Naissensis     Open Access  
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 5)
Acta Scientifica Naturalis     Open Access   (Followers: 2)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 5)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 7)
Adsorption Science & Technology     Full-text available via subscription   (Followers: 5)
Advanced Functional Materials     Hybrid Journal   (Followers: 50)
Advanced Science Focus     Free   (Followers: 3)
Advances in Chemical Engineering and Science     Open Access   (Followers: 53)
Advances in Chemical Science     Open Access   (Followers: 13)
Advances in Chemistry     Open Access   (Followers: 14)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 18)
Advances in Drug Research     Full-text available via subscription   (Followers: 22)
Advances in Enzyme Research     Open Access   (Followers: 9)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 8)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 15)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 8)
Advances in Materials Physics and Chemistry     Open Access   (Followers: 19)
Advances in Nanoparticles     Open Access   (Followers: 14)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15)
Advances in Polymer Science     Hybrid Journal   (Followers: 41)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 19)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Science and Technology     Full-text available via subscription   (Followers: 12)
African Journal of Bacteriology Research     Open Access  
African Journal of Chemical Education     Open Access   (Followers: 2)
African Journal of Pure and Applied Chemistry     Open Access   (Followers: 7)
Agrokémia és Talajtan     Full-text available via subscription   (Followers: 2)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
AMB Express     Open Access   (Followers: 1)
Ambix     Hybrid Journal   (Followers: 3)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 67)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 14)
American Journal of Chemistry     Open Access   (Followers: 26)
American Journal of Plant Physiology     Open Access   (Followers: 13)
American Mineralogist     Hybrid Journal   (Followers: 13)
Analyst     Full-text available via subscription   (Followers: 38)
Angewandte Chemie     Hybrid Journal   (Followers: 158)
Angewandte Chemie International Edition     Hybrid Journal   (Followers: 208)
Annales UMCS, Chemia     Open Access   (Followers: 1)
Annals of Clinical Chemistry and Laboratory Medicine     Open Access   (Followers: 1)
Annual Reports in Computational Chemistry     Full-text available via subscription   (Followers: 3)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 3)
Annual Reports Section B (Organic Chemistry)     Full-text available via subscription   (Followers: 8)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 12)
Annual Review of Food Science and Technology     Full-text available via subscription   (Followers: 14)
Anti-Infective Agents     Hybrid Journal   (Followers: 3)
Antiviral Chemistry and Chemotherapy     Hybrid Journal  
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7)
Applied Spectroscopy     Full-text available via subscription   (Followers: 23)
Applied Surface Science     Hybrid Journal   (Followers: 28)
Arabian Journal of Chemistry     Open Access   (Followers: 6)
ARKIVOC     Open Access   (Followers: 2)
Asian Journal of Biochemistry     Open Access   (Followers: 1)
Atomization and Sprays     Full-text available via subscription   (Followers: 3)
Australian Journal of Chemistry     Hybrid Journal   (Followers: 7)
Autophagy     Hybrid Journal   (Followers: 2)
Avances en Quimica     Open Access   (Followers: 1)
Biochemical Pharmacology     Hybrid Journal   (Followers: 10)
Biochemistry     Full-text available via subscription   (Followers: 283)
Biochemistry Insights     Open Access   (Followers: 5)
Biochemistry Research International     Open Access   (Followers: 6)
BioChip Journal     Hybrid Journal  
Bioinorganic Chemistry and Applications     Open Access   (Followers: 9)
Bioinspired Materials     Open Access   (Followers: 5)
Biointerface Research in Applied Chemistry     Open Access   (Followers: 2)
Biointerphases     Open Access   (Followers: 1)
Biology, Medicine, & Natural Product Chemistry     Open Access   (Followers: 1)
Biomacromolecules     Full-text available via subscription   (Followers: 19)
Biomass Conversion and Biorefinery     Partially Free   (Followers: 10)
Biomedical Chromatography     Hybrid Journal   (Followers: 6)
Biomolecular NMR Assignments     Hybrid Journal   (Followers: 3)
BioNanoScience     Partially Free   (Followers: 4)
Bioorganic & Medicinal Chemistry     Hybrid Journal   (Followers: 108)
Bioorganic & Medicinal Chemistry Letters     Hybrid Journal   (Followers: 93)
Bioorganic Chemistry     Hybrid Journal   (Followers: 10)
Biopolymers     Hybrid Journal   (Followers: 18)
Biosensors     Open Access   (Followers: 2)
Biotechnic and Histochemistry     Hybrid Journal   (Followers: 1)
Bitácora Digital     Open Access  
Boletin de la Sociedad Chilena de Quimica     Open Access  
Bulletin of the Chemical Society of Ethiopia     Open Access   (Followers: 2)
Bulletin of the Chemical Society of Japan     Full-text available via subscription   (Followers: 24)
Bulletin of the Korean Chemical Society     Hybrid Journal   (Followers: 1)
C - Journal of Carbon Research     Open Access   (Followers: 3)
Cakra Kimia (Indonesian E-Journal of Applied Chemistry)     Open Access  
Canadian Association of Radiologists Journal     Full-text available via subscription   (Followers: 2)
Canadian Journal of Chemistry     Hybrid Journal   (Followers: 10)
Canadian Mineralogist     Full-text available via subscription   (Followers: 3)
Carbohydrate Research     Hybrid Journal   (Followers: 26)
Carbon     Hybrid Journal   (Followers: 67)
Catalysis for Sustainable Energy     Open Access   (Followers: 6)
Catalysis Reviews: Science and Engineering     Hybrid Journal   (Followers: 8)
Catalysis Science and Technology     Free   (Followers: 6)
Catalysis Surveys from Asia     Hybrid Journal   (Followers: 3)
Catalysts     Open Access   (Followers: 7)
Cellulose     Hybrid Journal   (Followers: 7)
Cereal Chemistry     Full-text available via subscription   (Followers: 4)
ChemBioEng Reviews     Full-text available via subscription   (Followers: 1)
ChemCatChem     Hybrid Journal   (Followers: 8)
Chemical and Engineering News     Free   (Followers: 12)
Chemical Bulletin of Kazakh National University     Open Access  
Chemical Communications     Full-text available via subscription   (Followers: 70)
Chemical Engineering Research and Design     Hybrid Journal   (Followers: 23)
Chemical Research in Chinese Universities     Hybrid Journal   (Followers: 3)
Chemical Research in Toxicology     Full-text available via subscription   (Followers: 19)
Chemical Reviews     Full-text available via subscription   (Followers: 170)
Chemical Science     Open Access   (Followers: 21)
Chemical Technology     Open Access   (Followers: 16)
Chemical Vapor Deposition     Hybrid Journal   (Followers: 5)
Chemical Week     Full-text available via subscription   (Followers: 8)
Chemie in Unserer Zeit     Hybrid Journal   (Followers: 55)
Chemie-Ingenieur-Technik (Cit)     Hybrid Journal   (Followers: 25)
ChemInform     Hybrid Journal   (Followers: 8)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 6)
Chemistry & Biology     Full-text available via subscription   (Followers: 30)
Chemistry & Industry     Hybrid Journal   (Followers: 5)
Chemistry - A European Journal     Hybrid Journal   (Followers: 144)
Chemistry - An Asian Journal     Hybrid Journal   (Followers: 15)
Chemistry and Materials Research     Open Access   (Followers: 18)
Chemistry Central Journal     Open Access   (Followers: 4)
Chemistry Education Research and Practice     Free   (Followers: 5)
Chemistry in Education     Open Access   (Followers: 9)
Chemistry International     Hybrid Journal   (Followers: 2)
Chemistry Letters     Full-text available via subscription   (Followers: 45)
Chemistry of Materials     Full-text available via subscription   (Followers: 226)
Chemistry of Natural Compounds     Hybrid Journal   (Followers: 9)
Chemistry World     Full-text available via subscription   (Followers: 22)
Chemistry-Didactics-Ecology-Metrology     Open Access  
ChemistryOpen     Open Access   (Followers: 2)
Chemkon - Chemie Konkret, Forum Fuer Unterricht Und Didaktik     Hybrid Journal  
Chemoecology     Hybrid Journal   (Followers: 2)
Chemometrics and Intelligent Laboratory Systems     Hybrid Journal   (Followers: 15)
Chemosensors     Open Access  
ChemPhysChem     Hybrid Journal   (Followers: 9)
ChemPlusChem     Hybrid Journal   (Followers: 2)
ChemTexts     Hybrid Journal  
CHIMIA International Journal for Chemistry     Full-text available via subscription   (Followers: 2)
Chinese Journal of Chemistry     Hybrid Journal   (Followers: 6)
Chinese Journal of Polymer Science     Hybrid Journal   (Followers: 10)
Chromatographia     Hybrid Journal   (Followers: 24)
Chromatography Research International     Open Access   (Followers: 7)
Clay Minerals     Full-text available via subscription   (Followers: 9)
Cogent Chemistry     Open Access  
Colloid and Interface Science Communications     Open Access  
Colloid and Polymer Science     Hybrid Journal   (Followers: 10)
Colloids and Surfaces B: Biointerfaces     Hybrid Journal   (Followers: 8)
Combinatorial Chemistry & High Throughput Screening     Hybrid Journal   (Followers: 3)
Combustion Science and Technology     Hybrid Journal   (Followers: 18)
Comments on Inorganic Chemistry: A Journal of Critical Discussion of the Current Literature     Hybrid Journal   (Followers: 2)
Composite Interfaces     Hybrid Journal   (Followers: 6)
Comprehensive Chemical Kinetics     Full-text available via subscription   (Followers: 2)
Comptes Rendus Chimie     Full-text available via subscription  
Comptes Rendus Physique     Full-text available via subscription   (Followers: 1)
Computational and Theoretical Chemistry     Hybrid Journal   (Followers: 9)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 12)
Computational Chemistry     Open Access   (Followers: 2)
Computers & Chemical Engineering     Hybrid Journal   (Followers: 9)
Coordination Chemistry Reviews     Full-text available via subscription   (Followers: 2)
Copernican Letters     Open Access  
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 5)
Crystal Structure Theory and Applications     Open Access   (Followers: 3)
CrystEngComm     Full-text available via subscription   (Followers: 11)
Current Catalysis     Hybrid Journal   (Followers: 2)
Current Metabolomics     Hybrid Journal   (Followers: 5)
Current Opinion in Colloid & Interface Science     Hybrid Journal   (Followers: 9)
Current Research in Chemistry     Open Access   (Followers: 8)
Current Science     Open Access   (Followers: 56)
Dalton Transactions     Full-text available via subscription   (Followers: 20)
Detection     Open Access   (Followers: 2)
Developments in Geochemistry     Full-text available via subscription   (Followers: 2)
Diamond and Related Materials     Hybrid Journal   (Followers: 12)
Dislocations in Solids     Full-text available via subscription  
Doklady Chemistry     Hybrid Journal  
Drying Technology: An International Journal     Hybrid Journal   (Followers: 4)
Eclética Química     Open Access   (Followers: 1)
Ecological Chemistry and Engineering S     Open Access   (Followers: 4)
Ecotoxicology and Environmental Contamination     Open Access  
Educación Química     Open Access   (Followers: 1)
Education for Chemical Engineers     Hybrid Journal   (Followers: 5)
EJNMMI Radiopharmacy and Chemistry     Open Access  
Elements     Full-text available via subscription   (Followers: 2)
Environmental Chemistry     Hybrid Journal   (Followers: 9)
Environmental Chemistry Letters     Hybrid Journal   (Followers: 4)
Environmental Science & Technology Letters     Full-text available via subscription   (Followers: 5)

        1 2 3 | Last

Journal Cover Biomedical Chromatography
  [SJR: 0.572]   [H-I: 49]   [6 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0269-3879 - ISSN (Online) 1099-0801
   Published by John Wiley and Sons Homepage  [1576 journals]
  • Development and validation of an LC-MS/MS method for the simultaneous
           quantification of seven constituents in rat plasma and application in a
           pharmacokinetic study of the Zaoren Anshen prescription
    • Authors: Ajing Zhao; Li Zhang, Rong Li, Jiao Shang, Huihui Yi, Yuan Wang, Dian Zhang, Shixiang Wang, Minfeng Fang
      Abstract: A sensitive, specific and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of seven constituents of the Zaoren Anshen prescription (ZAP) in rat plasma after oral administration of the ZAP: spinosin, salvianic acid A, 6”’-feruloylspinosin, protocatechualdehyde, salvianolic acid B, schisandrin and deoxyschisandrin. The plasma samples and the internal standard (IS) sulfamethoxazole were extracted using acetonitrile. Chromatographic separation was performed with an Agilent HC-C18 column using a gradient elution profile and a mobile phase consisting of 0.01% formic acid in water (A) and acetonitrile (B). The analytes were quantified simultaneously in a single run using an ion trap mass spectrometer operated in the multiple reaction monitoring (MRM) mode and electrospray ion-source polarity in the positive and negative modes. The calibration curves for spinosin, salvianic acid A, 6”’-feruloylspinosin, protocatechualdehyde, salvianolic acid B, schisandrin and deoxyschisandrin were linear over the concentration ranges of 2.90-1160, 2.50-1000, 1.80-720, 0.65-260, 2.50-1000, 8.00-1600 and 1.30-520 ng/mL, respectively. The intra- and inter-day precisions in terms of relative standard deviation were less than 18.9%, and the accuracies in terms of relative error were within ±14.2%. Consequently, the proposed method was successfully applied to the pharmacokinetic analysis of these seven major active compounds in rats administered ZAP. These results will facilitate research aiming to predict the effectiveness of the optimal dose of ZAP and might be beneficial for the therapeutic use of ZAP in the clinical setting.
      PubDate: 2017-07-26T00:50:57.347327-05:
      DOI: 10.1002/bmc.4055
  • Quantitative determination of trigonelline in mice serum by means of
           hydrophilic interaction liquid chromatography-MS/MS analysis –
           application to a pharmacokinetic study
    • Authors: Damian Szczesny; Ewa Bartosińska, Julia Jacyna, Małgorzata Patejko, Danuta Siluk, Roman Kaliszan
      Abstract: Trigonelline (TRG) is a pyridine alkaloid found in fenugreek seeds and coffee beans. Most of the previous studies are concerning quantification of trigonelline along with other constituents in coffee herbs or beverages. Only a few are focused on its determination in animal or human tissues by applying different modes of HPLC with UV or MS detection. The aim of the study was to develop and validate fast and simple method for trigonelline determination in serum by use of hydrophilic interaction liquid chromatography with ESI-MS/MS detection. Separation of trigonelline was achieved on Kinetex HILIC column operated in 35°C with acetonitrile/ammonium formate (10 mM, pH = 3) buffer mixture (55:45, v/v) as the mobile phase. Developed method was successfully applied to determine trigonelline concentration in mice serum after intravenous administration of 10 mg/kg. The developed assay is sensitive (limit of detection = 1.5 ng/ml, limit of quantification = 5.0 ng/ml) and linear in concentration range from 5.0 to 250.0 ng/ml. Sample preparation is limited to deproteinization, centrifugation and filtration. The application of HILIC mode of chromatography with MS detection and selection of deuterated trigonelline as internal standard allowed to develop rapid and precise method of trigonelline quantification.
      PubDate: 2017-07-25T23:30:22.277162-05:
      DOI: 10.1002/bmc.4054
  • Residual dynamic and risk assessment of dimethomorph in Swiss chard grown
           in two different sites
    • Authors: Md. Humayun Kabir; A.M. Abd El-Aty, Md. Musfiqur Rahman, Hyung Suk Chung, Han Sol Lee, Mi-Ra Kim, Byung-Joon Chang, Jing Wang, Ho-Chul Shin, Jae-Han Shim
      Abstract: Residue analysis of dimethomorph in Swiss chard cultivated at two different locations under greenhouse conditions was conducted using high-performance liquid chromatography-ultraviolet detector (HPLC-UVD) and confirmed by tandem mass spectrometry (LC-MS/MS). The randomly collected samples (over 14 days) were extracted with acetonitrile and purified using a Florisil solid-phase extraction (SPE) cartridge. Linearity over a concentration range of 0.05–50.0 mg/L had an excellent coefficient of determination (R2) = 0.9996. Recovery rate ranged from 82.98 to 95.43% with relative standard deviations (RSDs) ≤ 5.12%, and limits of detection (LOD) and quantification (LOQ) were 0.003 and 0.01 mg/kg, respectively. The initial deposits (zero day [2-h post-application]) were considerably lower (7.57 and 8.55 mg/kg for Sites 1 and 2, respectively) than the maximum residue limit (MRL = 30 mg/kg) set by the Korean Ministry of Food and Drug Safety. The dissipation half-life was approximately the same, being 5.0 and 5.1 days for Sites 1 and 2, respectively. Risk assessment estimated as acceptable daily intake (ADI%) revealed a value of 0.084 or 0.094% (zero day) and 0.014% (10-days post-application), for Sites 1 and 2, respectively. The values indicated that dimethomorph could be safely used on Swiss chard, with no hazardous effects expected for Korean consumers.
      PubDate: 2017-07-21T08:55:41.749416-05:
      DOI: 10.1002/bmc.4053
  • Simultaneous determination and method validation of difenoconazole,
           propiconazole and pyraclostrobin in pepper and soil by LC−MS/MS in field
           trial samples from three provinces, China
    • Authors: Kunming Zheng; Banghua Meng, Sizhuo Wu, Haizhen Zhang, Fei Wang, Ying Cui, Song Zeng, Kankan Zhang, Deyu Hu
      Abstract: A liquid chromatography-electrospray ionization tandem mass spectrometry method was developed for simple and accurate detection of the fungicides difenoconazole, propiconazole and pyraclostrobin in peppers and soil. Three fungicides residues were extracted from samples by acetonitrile, cleaned up by dispersive solid phase extraction before instrumental analysis. The accuracy and precision of the method were evaluated by conducting intra- and inter-day recovery experiment. The limits of quantification and detection of difenoconazole, propiconazole and pyraclostrobin in pepper and soil were 0.005 and 0.0015 mg/kg, respectively. The recoveries were investigated by spiking pepper and soil at three levels, and were found to range from 79.62% to 103.15% for difenoconazole, 85.94% to 103.35% for propiconazole, and 80.14% to 97.69% for pyraclostrobin, with relative standard deviations below 6.5%. Field experiments were conducted in three locations in China. The half-lives of difenoconazole, propiconazole and pyraclostrobin were 5.3–11.5 days in peppers and 6.1–32.5 days in soil. At harvest, pepper samples were found to contain difenoconazole, propiconazole and pyraclostrobin well below the maximum residue limits of European Union at the interval of 21 days after last application following the recommended dosage.
      PubDate: 2017-07-19T04:50:22.585537-05:
      DOI: 10.1002/bmc.4052
  • Discrimination of Polygoni Multiflori Radix and Cynanchi Auriculati Radix
           using ultra-high performance liquid chromatography fingerprints and
           chemical pattern recognition
    • Authors: Lili Sun; Meng Wang, Yali Liu, Huijie Zhang, Yanan Liu, Xiaoliang Ren, Yanru Deng
      Abstract: In this work, a strategy was proposed to discriminate Polygoni Multiflori Radix (PMR) and its adulteration (Cynanchi Auriculati Radix, CAR). The ultra-high performance liquid chromatography (UHPLC) fingerprints were established to analyze samples containing PMR, CAR and mixtures simultaneously. Multivariate classification methods were applied to analyze the obtained UHPLC fingerprints, including principal component analysis (PCA), partial least square discriminant analysis (PLS-DA), soft independent modeling of class analogy (SIMCA), support vector machine discriminant analysis (SVMDA), and counter-propagation artificial neural network (CP-ANN). A plot of PCA score showed that PMR and CAR samples belonged to separate clusters (PMR class and CAR class), and samples of mixtures were located near PMR or CAR classes. Analysis by PLS-DA, SVMDA and CP-ANN performed well for recognition and prediction in terms of PMR and CAR samples. Moreover, the PLS-DA method performed best in the detection of adulterated samples, even if the adulterant is about 25%.
      PubDate: 2017-07-19T04:40:21.18149-05:0
      DOI: 10.1002/bmc.4050
  • Application of headspace solid-phase microextraction followed by gas
           chromatography coupled with mass spectrometry (SPME/GC-MS) to determine
           esters of carboxylic acids and other volatile compounds in D. maculatus
           and D. ater lipids
    • Authors: Magdalena Cerkowniak; Mieczysława I. Boguś, Emilia Włóka, Piotr Stepnowski, Marek Gołębiowski
      Abstract: A constant problem in veterinary medicine, human healthcare, agriculture, forestry or horticulture is the large number of pests, and the lack of effective methods to combat them which cause no harm to the rest of the environment. It is recommended and desired to reduce the use of chemicals and increase the use of agents based on the knowledge acquired in the field of biology, chemistry, and agrochemicals. To learn the defense mechanisms of insects we should consider not only the site of their physiological ability to protect against external factors (cuticle), but also check the possibility of chemical protection, formed by all compounds on the surface and in the body of insects.In this study, a procedure was developed to determine the esters of carboxylic acids in insect lipids. Headspace solid-phase microextraction was followed by gas chromatography coupled with gas spectrometry (GC-MS). At first, the best conditions were selected for the analysis to obtain the best chromatographic separation. An RTx-5 column was used for this purpose. Polydimethylsiloxane/divinylbenzene and polyacrylate fibers (PDMS/DVB and PA) were used to isolate acid esters. PDMS/DVB fiber achieved the best conditions for the extraction; the extraction time was 50 min, the extraction temperature - 105 °C, and the desorption time - 10 min in 230 °C. These SPME conditions were used to analyze volatile compounds extracted from insects belonging to the Dermestidae family.
      PubDate: 2017-07-19T02:35:22.245139-05:
      DOI: 10.1002/bmc.4051
  • Chemical UPLC-ESI-MS/MS profiling of aconitum alkaloids and their
           metabolites in rat plasma and urine after oral administration of Aconitum
           carmichaelii Debx. root extract
    • Authors: Mingjie Zhang; Manman Wang, Jiajia Liang, Yongqing Wen, Zhili Xiong
      Abstract: In this paper, an ultra high performance liquid chromatography tandem mass spectrometric (UPLC-ESI-MS/MS) method in positive ion mode was established to systematically identify and to compare the major aconitum alkaloids and their metabolites in rat plasma and urine after oral administration of Fuzi extract.A total twenty-nine components including twenty-five C19-diterpenoid alkaloids and four C20-diterpenoid alkaloids were identified in Fuzi extract. Thirteen of the parent components and five metabolites were detected in rat plasma and sixteen parent compounds and six metabolites in urine. These parent components found in rat plasma and urine were mainly C19-diterpenoid alkaloids.All of the metabolites in vivo were demethylated metabolites (phase I metabolites), which suggested that demethylation was the major metabolic pathway of aconitum alkaloids in vivo. A comparison of the parent components in rat plasma and urine revealed that 3-deoxyacontine was found in plasma but not in urine, while kalacolidine, senbusine and 16-β-hydroxycardiopetaline existed in urine but not in plasma, which indicated that most alkaloids components were disposed and excreted in prototype form. This research provides some important information for further metabolic investigations of Fuzi in vivo.
      PubDate: 2017-07-18T03:20:54.699557-05:
      DOI: 10.1002/bmc.4049
  • Pharmacokinetics and tissue distribution study of clevidipine and its
           primary metabolite H152/81 in rats
    • Authors: Yan Wang; Lanting Zhao, Tengfei Li, Wen Yang, Qian Li, Luning Sun, Li Ding
      Abstract: This present study was designed to investigate the pharmacokinetic profiles and tissue distribution characteristics of clevidipine and its primary metabolite H152/81 in rats following a single intravenous administration of clevidipine butyrate injectable emulsion (CBIE). For this study, a sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established and validated for the simultaneous quantitation of clevidipine and H152/81 in rat whole blood and various tissues. A Hedera ODS-2 column with two gradient elution programs was employed for the troubleshooting of matrix effect on the detection of analytes among different biological samples. The experimental data showed that clevidipine represented quick elimination from blood with t1/2 of about 4.3 min and rapid distribution in all of the investigated tissues after administration, the highest concentration of clevidipine was found in the heart whereas the lowest concentration was detected in the liver. Besides, clevidipine was almost undetectable in most tissues except for heart and brain at 90 min post-dosing, suggesting that there was no apparent long-term accumulation in rat tissues. For H152/81, the Cmax of 3714 ± 319 ng/mL occurred at 0.129 ± 0.048 h (Tmax), the t1/2 was 10.08 ± 1.45 h and AUC0-t was 42091 ± 3812 ng∙h/mL after drug administration. In addition, H152/81 was found at significant concentration levels in all the tissues, in descending order of lung, kidney, heart, liver, spleen and brain at each time point. The results of current study offer useful clues for better understanding the distribution and metabolism of CBIE in vivo.
      PubDate: 2017-07-14T05:55:19.331633-05:
      DOI: 10.1002/bmc.4048
  • Screening and identification of metabolites of two kinds of main active
           ingredients and hepatotoxic pyrrolizidine alkaloids (HPAs) in rat after
           lavage Farfarae Flos extract by UHPLC-Q-TOF-MS mass spectrometry
    • Authors: Xiaoye Cheng; Man Liao, Xinpeng Diao, Yupeng Sun, Lantong Zhang
      Abstract: Farfarae Flos, the dried flower buds of Tussilago farfara L., is usually used to treat coughs, bronchitic and asthmatic conditions as an important traditional Chinese medicine. Tussilagone and methl butyric acid tussilagin ester are seen as representatives of two kinds of active substances. Besides, the pyrrolizidine alkaloids (HPAs), mainly senkirkine and senecionine, presented in the herb can be hepatoxic. In this study, a rapid and sensitive ultra high performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) method is successfully applied to identify the metabolites of tussilagone, methl butyric acid tussilagin ester , senkirkine and senecionine. The results showed that a total of 35, 37, 18 and 9 metabolites of tussilagone, methl butyric acid tussilagin ester, senkirkine and senecionine in rats were tentatively identified. Hydrolysis, oxidation, reduction and demethylation were the major metabolic reactions for tussilagone and methl butyric acid tussilagin ester. The main biotransformation routes of senkirkine and senecionine were identified as demethylation, N-methylation, oxidation and reduction. This study is the first reported analysis and characterization of the metabolites and the proposed metabolic pathways might provide further understanding of the metabolic fate of the chemical constituents after oral administration of Farfarae Flos extract in vivo.
      PubDate: 2017-07-12T20:00:26.338401-05:
      DOI: 10.1002/bmc.4047
  • An LC-MS/MS method for quantitation of cyanidin-3-O-glucoside in rat
           plasma: Application to a comparative pharmacokinetic study in normal and
           streptozotocin-induced diabetic rats
    • Authors: Chunxia Yang; Qiuhua Wang, Shenbao Yang, Qiong Yang, Ying Wei
      Abstract: A sensitive and reliable liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed to determine cyanidin-3-O-glucoside (Cy-3G) in normal and streptozotocin-induced diabetic rat plasma. Chromatographic separation was carried out on a ZORBAX SB-C18 (50 mm × 4.6 mm, 5 μm) column and mass spectrometric analysis was performed using a Thermo Finnigan TSQ Quantum Ultra triple-quadrupole mass spectrometer coupled with an ESI source in the negative ion mode. Selected reaction monitoring (SRM) mode was applied for quantification using target fragment ions m/z 447.3285.2 for Cy-3G, and m/z 463.0300.1 for quercetin-3-O-glucoside (internal standard). Calibration curve was linear over the range of 3.00–2700 ng/mL (r2 ≥ 0.99) with the lower limit of quantitation (LLOQ) at 3.00 ng/mL. Intra- and inter-day precision was below 14.5% and mean accuracy was from –11.5% to 13.6%. Stability testing showed that Cy-3G remained stable during the whole analytical procedure. After validation, the assay was successfully used to support a preclinical pharmacokinetic comparison of Cy-3G between normal and diabetic rats. Results indicated that diabetes mellitus significantly altered the in vivo pharmacokinetic characteristics of Cy-3G after oral administration in rats.
      PubDate: 2017-07-06T10:45:25.567379-05:
      DOI: 10.1002/bmc.4042
  • Characterization and discrimination of raw and vinegar-baked Bupleuri
           Radix based on UHPLC–Q-TOF-MS coupled with multivariate statistical
    • Authors: Tianli Lei; Shifeng Chen, Kai Wang, Dandan Zhang, Lin Dong, Chongning Lv, Jing Wang, Jincai Lu
      Abstract: Bupleuri Radix is a commonly used herb in clinic, and raw and vinegar-baked Bupleuri Radix are both documented in the Pharmacopoeia of People's Republic of China. According to the theories of traditional Chinese medicine, Bupleuri Radix possesses different therapeutic effects before and after processing. However, the chemical mechanism of this processing is still unknown. In this study, an ultra-high performance liquid chromatography with quadruple time-of-flight mass spectrometry coupled with multivariate statistical analysis including principal component analysis and orthogonal partial least square-discriminant analysis was developed to holistically compare the difference between raw and vinegar-baked Bupleuri Radix for the first time. As a result, 50 peaks in raw and processed Bupleuri Radix were detected, respectively, and a total of 49 peaks chemical compounds were identified. Saikosaponin a, saikosaponin d, saikosaponin b3, saikosaponin e, saikosaponin c, saikosaponin b2, saikosaponin b1, 4"-O-acetyl-saikosaponin d, hyperoside and 3', 4'-dimethoxy quercetin were explored as the potential markers of raw and vinegar-baked Bupleuri Radix. This study has been successfully applied for global analysis of raw and vinegar processed samples. Furthermore, the underlying hepatoprotective mechanism of Bupleuri Radix was predicted, which was related to the changes of chemical profiling.
      PubDate: 2017-07-05T06:15:19.133549-05:
      DOI: 10.1002/bmc.4044
  • Determination of Tigecycline in Human Plasma by LC-MS/MS and its
           Application to Population Pharmacokinetics Study in Chinese Patients with
           Hospital-acquired Pneumonia
    • Authors: Rong Shao; Xingang Li, Yangmin Hu, Jinliang Chen, Honggang Lou, Haibin Dai
      Abstract: A selective, sensitive, and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of Tigecycline (TGC) in human plasma, using Tigecycline-d9 as an internal standard (IS). Analytical samples were prepared using a protein precipitation method coupled with a concentration process. The analyte and IS were separated on a reversed-phase Waters Acquity UPLC® BEH-C18 column (2.1 mm × 50 mm ID, 1.7 μm) with a flow rate of 0.25 ml/min. The mobile phase consisted of water, containing 0.2% formic acid (v/v) with 10 mM ammonium formate (A) and acetonitrile (B). The mass spectrometer was operated in selected reaction monitoring (SRM) mode through electrospray ionization ion mode using the transitions of m/z 586.2513.1 and m/z 595.1514.0 for TGC and IS, respectively. The linearity of the method was in the range of 10-5000 ng/ml. Intra- and inter-batch precision (% CV) for TGC were less than 9.27%, and the accuracy ranged from 90.06% to 107.13%. This method was successfully applied to the analysis of samples from hospital-acquired pneumonia (HAP) patients treated with TGC, and a validated population pharmacokinetic (PPK) model was established. This developed method could be quite useful to predict PK parameters and valuable for further PK/PD studies.
      PubDate: 2017-07-05T06:00:37.167614-05:
      DOI: 10.1002/bmc.4045
  • Development and Validation of a High-Performance Liquid Chromatography
           Method for the Quantification of Talazoparib in Rat Plasma: Application to
           Plasma Protein Binding Studies
    • Authors: Mahendra Kumar Hidau; Srikanth Kolluru, Srinath Palakurthi
      Abstract: A sensitive and selective RP-HPLC method has been developed and validated for the quantification of a highly-potent poly ADP ribose polymerase (PARP) inhibitor talazoparib (TZP) in rat plasma. Chromatographic separation was performed with isocratic elution method. Absorbance for TZP was measured with UV detector (SPD-20A UV-VIS) at λmax of 227 nm. Protein precipitation method was used to extract the drug form plasma samples using methanol: acetonitrile (65:35) as a precipitating solvent. Method was shown sensitive and reproducible over 100-2000 ng/mL linearity range with LLQC of 100 ng/mL. TZP recovery was found to be>85%. Following analytical method development and validation, it was successfully employed to determine the plasma protein binding of TZP. It was found that TZP has high protein binding in rat plasma (95.76 ± 0.38 %) as determined by dialysis method.
      PubDate: 2017-07-05T05:40:19.478367-05:
      DOI: 10.1002/bmc.4046
  • Validated LC-MS/MS method for quantitation of demethylbellidifolin in rat
    • Authors: Jie Zhang; Huiyu Yan, Xiaoyu Qu, Wei Zhou
      Abstract: Demethylbellidifolin, a major xanthone compound of Swertia davidi Franch, showed many beneficial pharmacological effects including antioxidation, anti-inflammation, anti-fibrosis, and cardiovascular protection effects. In this research, a rapid and sensitive LC-MS/MS method for the quantitative analysis of demethylbellidifolin in rat plasma was developed. The demethylbellidifolin and internal standard of aurantio-obtusin were extracted from 50 μL of rat plasma samples with ethyl acetate, then the dried residue was reconstituted and injected in an HPLC system with ZORBAX SB-C18 analytical column (2.1 mm × 100 mm, 3.5 μm) and eluted with the mobile phase consisting of methanol and 0.2% formic acid aqueous solution (80:20, v/v). Quantification was performed by a TSQ QUANTUM ULTRA mass spectrometer in negative ESI using SRM mode of the transitions m/z 259.1215.1 for demethylbellidifolin and 329.0314.2 for the IS. Excellent linearity was observed between 1.92 and 960 ng/mL with a limit of quantitation of 1.92 ng/mL. Intra- and inter-day precision (RSD) values of QC samples were both less than 8.3%. This study was successfully utilized for the pharmacokinetic profiles of demethylbellidifolin in rats after oral or intravenous administration. The oral bioavailability of demethylbellidifolin was determined to be 3.6%.
      PubDate: 2017-07-05T05:00:19.448471-05:
      DOI: 10.1002/bmc.4043
  • Issue information
    • Abstract: No abstract is available for this article.
      PubDate: 2017-07-05T04:29:43.37472-05:0
      DOI: 10.1002/bmc.3842
  • Determination of silodosin and its active glucuronide metabolite,
           KMD-3213G in human plasma by LC-MS/MS for a bioequivalence study
    • Authors: Priyanka A. Shah; Pranav S. Shrivastav
      Abstract: A sensitive and selective liquid chromatography–tandem mass spectrometry (LC–MS/MS) method is described for the simultaneous determination of silodosin (SLD) and its active metabolite silodosin β-D-glucuronide (KMD-3213G) in human plasma. Liquid-liquid extraction of plasma samples was carried out with ethyl acetate and methyl tert-butyl ether solvent mixture using deuterated analogs as internal standards. The extraction recovery of SLD and KMD-3213G was in the range of 90.8-93.4 % and 87.6-89.9 % respectively. The extracts were analyzed on Symmetry C18 (50 × 4.6 mm, 5 μm) column under gradient conditions using 10 mM ammonium formate in water and methanol: acetonitrile (40:60, v/v), within 6.0 min. For MS/MS measurements, ionization of the analytes was carried out in the positive ionization mode and the transitions monitored were m/z 496.1 261.2 for SLD and m/z 670.2 494.1 for KMD-3213G. The method showed good linearity, accuracy, precision and stability in the range of 0.10–80.0 ng/mL for SLD and KMD-3213G. The IS-normalized matrix factors obtained were highly consistent, ranging from 0.962-1.023 for both the analytes. The method was used to support a bioequivalence study of SLD and its metabolite in healthy volunteers after oral administration of 8 mg silodosin capsules.
      PubDate: 2017-07-03T03:20:53.77541-05:0
      DOI: 10.1002/bmc.4041
  • Analytical methodologies for the stereoselective determination of
           fluoxetine: an overview
    • Authors: Gabriel Hancu; Melania Cârcu-Dobrin, Monica Budău, Aura Rusu
      Abstract: Fluoxetine is a widely used antidepressant belonging to the selective serotonin reuptake inhibitor class; used in the treatment of major depression, obsessive compulsive, premenstrual dysphoric, panic and post-traumatic stress disorders. Fluoxetine is an optical active pharmaceutical substance, which is used as a racemate in therapy, but stereospecific interactions associated with the serotonin-reuptake carrier, for both the parent drug and its active metabolite, norfluoxetine, has been described in the literature.Therefore, the stereoselective analysis of fluoxetine and norfluoxetine is important in order to characterize the pharmacokinetic and pharmacodynamic profile of the analytes. Several chromatographic and electrophoretic methods have been published in literature for the chiral discrimination of fluoxetine enantiomers from different matrix. The purpose of the current review is to provide a systematic survey of the analytical techniques used for the chiral determination of fluoxetine and norfluoxetine covering a period of approximately 25 years.
      PubDate: 2017-07-03T03:00:19.996376-05:
      DOI: 10.1002/bmc.4040
  • A UPLC-TOF/MS-based metabolomics study of rattan stems of Schisandra.
           chinensis effects on Alzheimer's disease rats model
    • Authors: Bing-you Yang; Jin-yan Tan, Yan Liu, Bo Liu, Shuang Jin, Hong-wei Guo, Hai-xue Kuang
      Abstract: A UPLC-TOF/MS-based metabolomics method was established to explore the therapeutic mechanisms of rattan stems of Schisandra. Chinensis (SCS) on Alzheimer's disease (AD). Experimental AD model was induced by intra-hippocampal Aβ1-42 injection in rats. Cognitive function and oxidative stress condition in brain of AD rats were assessed using Morris water maze tests and antioxidant assays (MDA, SOD and GSH-Px), respectively. UPLC-TOF/MS combined with multivariate statistical analysis were conducted to study the changes of metabolic networks in serum of rats. The results indicated AD model was established successfully and the inducement of Aβ1-42 caused a decline in spatial learning and memory of rats. The injection of Aβ1-42 in rat brains significantly elevated the level of MDA, and reduced SOD and GSH-Px activities. In addition, SCS showed significant anti-AD effects on model rats. A total of 30 metabolites were finally identified as potential biomarkers of AD and 14 of them had a significant recovery compared with AD model after SCS administration. Changes in AD metabolite profiling were restored into different levels through regulating 13 pathways. This was first report of the use of UPLC-TOF/MS-based serum metabolomics method to investigate therapeutic effects of SCS on AD, and enriched the potential biomarkers and metabolic networks of AD.
      PubDate: 2017-06-29T22:41:19.558447-05:
      DOI: 10.1002/bmc.4037
  • Elevated Levels of Liver Methylglyoxal and D-lactate in Early-Stage
           Hepatitis in Rats
    • Authors: Wen-Chuang Wang; Chu-Kuang Chou, Ming-Cheng Chuang, Yi-Chieh Li, Jen-Ai Lee
      Abstract: Methylglyoxal (MGO) is highly cytotoxic and its levels are elevated in diabetes, nephropathy, and atherosclerosis. However, it has never been studied in liver disease. For this reason, we aimed to assess the levels of MGO and its metabolite D-lactate in an early hepatitis model. Wistar rats were administered CCl4 (0.75 ml/Kg, i.p.) to induce hepatitis. In either CCl4-treated or untreated rats, AST and ALT levels did not change over the course of the study, indicating that significant liver damage did not occur following CCl4 treatment. However, the levels of MGO and D-lactate, were higher in the livers of CCl4 -treated animals than in untreated animals (MGO: 128.2 ± 18.8 and 248.1 ± 64.9 μg/g protein, p < 0.01; D-lactate: 0.860 ± 0.040 and 1.293 ± 0.078 μmol/g protein, respectively p < 0.01). Furthermore, in untreated and treated animals, serum D-lactate levels were 57.65 ± 2.59 and 92.16 ± 16.69 μM and urine D-lactate levels were 1.060 ± 0.007 and 1.555± 0.366 μmol/mg UCr, respectively (p < 0.01). These data show that in this model of early stage liver damage, the levels of MGO and its metabolite D-lactate are elevated and that D-lactate could be useful as a reference marker for the early stage of hepatitis.
      PubDate: 2017-06-29T22:41:16.807575-05:
      DOI: 10.1002/bmc.4039
  • Application of Gas and Liquid chromatography coupled to time-of-flight
           mass spectrometry in pesticides Multi-residue analysis
    • Authors: Abdalla Ahmed Elbashir; Hassan Y. Aboul-Enein
      Abstract: Analysis of pesticide residues in water and food matrices are active research area closely related to food safety and environmental issues. In this aspect mass spectrometry (MS) coupled to gas chromatography (GC) and liquid chromatography (LC) has been increasingly used in the analysis of pesticides residues in water and food. The increasing interest in application of high resolution mass spectrometry (HRMS) with time-of-flight (TOF) and the hybrid QqTOF in the pesticides analysis is due to its capability of performing both targeted and non-targeted analysis. This article discusses an overview of the application of GC-TOF-MS and LC-TOF-MS in water and food matrices.
      PubDate: 2017-06-29T22:41:12.023137-05:
      DOI: 10.1002/bmc.4038
  • Metabolomics revealed the toxicity of cationic liposomes in HepG2 cells
           using UHPLC-Q-TOF/MS and multivariate data analysis
    • Authors: Jing Yu; Hai Zhang, Ying Li, Sen Sun, Jie Gao, Yanqiang Zhong, Duxin Sun, Guoqing Zhang
      Abstract: Cationic liposomes (CLs) are novel non-viral vectors widely used for delivering drugs or genes. However, applications of CLs are largely hampered by their cytotoxicity, partly because the potential mechanism underlying the cytotoxicity of CLs remains unclear. The aim of the present study was to explore the underlying mechanism of cytotoxicity induced by CLs on HepG2 cells. Differential metabolites were identified and quantified using ultra-liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). The toxicity of CLs on HepG2 cells was evaluated by multivariate data analysis and statistics. Additionally, CCK-8 assay, heatmap, pathway and co-expression network were carried out to explore the relations between the metabolites and the pathways. The results showed a dose-dependent toxic effect of CLs on HepG2 cells, with an IC50 value of 119.9 μg/ml. Multivariate statistical analysis identified 42 potential metabolites between CLs-exposure and control groups. Pathway analysis showed significant changes in pathways involving amino acid metabolism, energy metabolism, lipid metabolism and oxidative stress in CLs-exposure group vs. control group. Metabolites related to the above-mentioned pathways included phenylalanine, methionine, creatine, oxalacetic acid, glutathione (GSH), oxidized glutathione (GSSG), choline phosphate and several unsaturated fatty acids, indicating that cells were disturbed in amino acid metabolism, energy and lipid supply when CLs exposure-induced injury occurred. It is concluded that CLs may induce cytotoxicity by enhancing ROS in vitro, affect the normal process of energy metabolism, disturb several vital signaling pathways and finally induce cell death.
      PubDate: 2017-06-29T22:40:42.448923-05:
      DOI: 10.1002/bmc.4036
  • Review of HPLC and LC-MS/MS assays for the determination of various
           non-steroidal anti-androgens (NSAA) used in the treatment of prostate
    • Authors: P.S. Suresh; Nuggehally R. Srinivas, Ramesh Mullangi
      Abstract: Prostate cancer is the most common cancer and one of the leading causes for cancer deaths in men. One of the commonly used approaches to treat metastatic prostate cancer was via first generation non-steroidal anti-androgens (NSAA) namely flutamide, nilutamide, bicalutamide and topilutamide. Most of the prostate cancer patients who are initially responsive develop a most aggressive form of disease called castration-resistant prostate cancer (CRPC). Second generation NSAA receptor antagonists (enzalutamide, apalutamide and darolutamide) are emerging as additional new options to treat CRPC. The objective of this work was to review the literature on the bioanalytical methods for the quantification of first and second generation NSAA inhibitors in clinical (human plasma) and preclinical (mouse plasma, rat plasma, urine and tissue homogenates etc.) studies along with relevant case studies for some chosen drugs. Based on the review, it was concluded that the published methodologies using either HPLC or LC-MS/MS are well suited for the quantification of NSAA inhibitors in various biological fluids to delineate pharmacokinetic data.
      PubDate: 2017-06-21T07:06:05.385909-05:
      DOI: 10.1002/bmc.4034
  • A highly sensitive LC-MS/MS method for simultaneous determination of
           glycyrrhizin and its active metabolite glycyrrhetinic acid: application to
           a human pharmacokinetic study after oral administration
    • Authors: Tsuneharu Suzuki; Michiko Tsukahara, Yuko Akasaka, Hideo Inoue
      Abstract: A highly sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of glycyrrhizin (GL) and its active metabolite, glycyrrhetinic acid (GA) from human plasma was validated and applied to a human pharmacokinetic study. The analytes were extracted from human plasma using an Oasis MAX cartridge and chromatographic separation was performed on an Inertsil ODS-3 column. The detection was performed using an API 4000 mass spectrometer operating in the positive electrospray ionization mode. Selected ion monitoring transitions of m/z 823453 for GL and m/z 471149 for GA were obtained. The response was a linear function of concentration over the ranges of 0.5–200 ng/mL for GL and 2–800 ng/mL for GA (both R2> 0.998). Using this method, pharmacokinetics of GL after single oral administration of a clinical dose (75 mg) to six healthy male Japanese volunteers were evaluated. GL was detected in the plasma of all subjects and the average Cmax was 24.8 ± 12.0 ng/mL. In contrast, Cmax of GA was 200.3 ± 60.3 ng/mL, i.e., ~8-fold higher than that of GL. This is the first report clarifying pharmacokinetic profiles of GL and GA simultaneously at a therapeutic oral dose of a GL preparation.
      PubDate: 2017-06-17T16:44:31.878648-05:
      DOI: 10.1002/bmc.4032
  • Development of a HPLC method for determination of four UV filters in
           sunscreen and its application to skin penetration studies
    • Authors: Carla Souza; Patrícia M.B.G. Maia Campos
      Abstract: This study describes the development, validation and application of a high-performance liquid chromatography (HPLC) method for the simultaneous determination of the in vitro skin penetration profile of four UV filters on porcine skin. Experiments were carried out on a gel-cream formulation containing the following UV filters: diethylamino hydroxybenzoyl hexyl benzoate (DHHB), bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT), methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT) and ethylhexyl triazone (EHT). The HPLC method demonstrated suitable selectivity, linearity (10.0 - 50.0 μg/mL), precision, accuracy and recovery from porcine skin and sunscreen formulation. The in vitro skin penetration profile was evaluated using Franz vertical diffusion cells for 24 h after application on porcine ear skin. None of the UV filters penetrated the porcine skin. Most of them stayed on the skin surface (>90%) and only BEMT, EHT and DHHB reached the dermis plus epidermis layer. These results are in agreement with previous results in the literature. Therefore, the analytical method was useful to evaluate the in vitro skin penetration of the UV filters and may help to the development of safer and effective sunscreen products.
      PubDate: 2017-06-17T16:43:58.215591-05:
      DOI: 10.1002/bmc.4029
  • Lansoprazole-sulphide, pharmacokinetics of this promising anti-tuberculous
    • Authors: Sipho Mdanda; Sooraj Baijnath, Adeola Shobo, Sanil D. Singh, Glenn E.M. Maguire, Hendrik G. Kruger, Per I. Arvidsson, Tricia Naicker, Thavendran Govender
      Abstract: Lansoprazole (LPZ) is a commercially available proton-pump inhibitor (PPI) whose primary metabolite, lansoprazole sulphide (LPZS) was recently reported to have in vitro and in vivo activity against M. tb. It was also reported that a 300 mg kg-1 oral administration of LPZS was necessary to reach therapeutic levels in the lung, with the equivalent human dose being unrealistic. A validated liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for the simultaneous quantification LPZ and LPZS in rat plasma and lung homogenates, was developed. We administered 15 mg kg-1 oral doses of LPZ to a healthy rat model to determine the pharmacokinetics of its active metabolite, LPZS, in plasma and lung tissue. We found that the LPZS was in amounts that were below the limit of quantification. This prompted us to administer the same dose of LPZS to the experimental animals intraperitoneally (i.p.). Using this approach, we found high amounts of LPZS in plasma and lung, 7841.1 and 9761.2 ng mL-1 respectively, which were significantly greater than its MIC for M. tb. While oral and i.p. administration of LPZ resulted in significant amounts of it in the lung, it does not undergo sufficient cellular conversion to its anti-TB metabolite. However, when LPZS itself is administered i.p., significant amounts penetrate the tissue. These results have implications for future in vivo studies exploring the potential of LPZS as an antiTB compound.
      PubDate: 2017-06-17T16:43:56.570945-05:
      DOI: 10.1002/bmc.4035
  • LC-MS/MS characterization, anti-inflammatory effects, and antioxidant
           activities of polyphenols from different tissues of Korean Petasites
           japonicus (Meowi)
    • Authors: Jin Young Choi; Kebede Taye Desta, Venu Venkatarame Gowda Saralamma, Sung Joong Lee, Soo Jung Lee, Seong Min Kim, Anjugam Paramanantham, Ho Jeong Lee, Yun-Hi Kim, Ho-Chul Shin, Jae-Han Shim, Sung Chul Shin, Gon-Sup Kim, A.M. Abd El-Aty
      Abstract: The Korean Petasites japonicus is a perennial plant used in folk medicine as a remedy for many diseases and popularly consumed as spring greens. Ten polyphenols were characterized from the leaves, stems, and roots of this plant via high-performance liquid chromatography-tandem mass spectrometry. Individual polyphenols were quantified for the first time using calibration curves of six structurally related external standards. Validation data indicated that correlation coefficients (R2) were ≥ 0.9702 for all standards. Recoveries measured at 50 and 100 mg/L were 80.0–91.9% and 80.3–105.3%, respectively. Precisions at these two concentration levels were 0.7–6.1% and 1.1–5.5%, respectively. The total number of identified components was largest for the leaves and smallest for the stems. The leaf and root polyphenolic extracts showed anti-inflammatory effects by inducing LPS-activated COX-2 and iNOS protein levels in mouse macrophage RAW 264.7 cells. The antioxidant capacity of the polyphenols, when evaluated for DPPH (α,α-diphenyl-β-picrylhydrazyl)ˑ, ABTS+ (2-2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), superoxide radical scavenging activities, and in ferric reducing ability of plasma (FRAP) assays, was highest in the leaf and lowest in the stem. This trend suggests the antioxidant capacities depend primarily on polyphenol concentration in each tissue. The current findings suggest that polyphenols derived from Petasites japonicas tissues could have the potential as functional health foods.
      PubDate: 2017-06-17T16:43:51.844714-05:
      DOI: 10.1002/bmc.4033
  • Quantification of β-eudesmol in rat plasma using LC-MS/MS and its
           application to a pharmacokinetic study
    • Authors: Ligang Jiang; Chunyang Zhang, Haiping Li
      Abstract: A sensitive and specific LC-MS/MS assay for determination of β-eudesmol in rat plasma was developed and validated. After liquid-liquid extraction with ethyl ether, the analyte and IS were separated on a Capcell Pak C18 column (50 × 2.0 mm, 5 μm) by isocratic elution with acetonitrile-water-formic acid (77.5:22.5:0.1, v/v/v) as the mobile phase at a flow rate of 0.4 mL/min. An ESI source was applied and operated in positive ion mode; selected reaction monitoring (SRM) scan was used for quantification by monitoring the precursor-product ion transitions of m/z 245.1163.1 for β-eudesmol and m/z 273.481.2 for IS. Good linearity was observed in the concentration range of 3–900 ng/mL for β-eudesmol in rat plasma. Intra-day and inter-day precision and accuracy were both within ±14.3%. This method was applied for pharmacokinetic studies after intravenous bolus of 2.0 mg/kg or intragastric administration of 50 mg/kg β-eudesmol in rats.
      PubDate: 2017-06-17T16:43:22.3121-05:00
      DOI: 10.1002/bmc.4023
  • A validated UHPLC-MS/MS method for the measurement of riluzole in plasma
           and myocardial tissue samples.
    • Authors: Suzanne L. Parker; Yarmarly C. Guerra Valero, Jeffrey Lipman, Steven Weiss, Camilla Smith, Lyndal Russell, Paul Smith, Jason A. Roberts, Steven C. Wallis
      Abstract: Through blocking the cardiac persistent sodium current, riluzole has the potential to prevent myocardial damage post cardiac bypass surgery. A sensitive UHPLC–MS/MS method was developed and validated for quantitation of riluzole and 5-methoxypsoralen in human plasma and myocardial tissue homogenate using a liquid–liquid extraction with dichloromethane. The chromatographic separation was achieved using Shimadzu Shim-pack XR-ODS III, 2.0 x 50 mm, 1.6 μm column with a gradient mobile phase comprising of methanol and ammonium acetate buffer pH 3.6 in purified water. The analyte and internal standard were separated within 3.5 minutes. Riluzole quantitation was achieved using the mass transitions of 235 to 138 for riluzole and 217 to 156 for 5MOP. The method was linear for riluzole plasma concentrations from 0.2 to 500 ng/mL and myocardial tissue homogenate concentrations from 0.2 to 100 ng/mL. The method developed was successfully applied to a clinical study for patients receiving riluzole while undergoing cardiac bypass surgery.
      PubDate: 2017-06-17T16:39:01.256242-05:
      DOI: 10.1002/bmc.4030
  • Pharmacokinetic comparison of two phenolic acids after oral administration
           of Typhae Pollen to normal rats and rats with acute cold blood stasis
    • Authors: Yingni Pan; Wenjie Zhang, Wei Zhang, Xuewei Bai, Shumeng Ren, Jiang Zheng, Dongmei Wang, Xiaoqiu Liu
      Abstract: Typhae Pollen (TP), dried pollen of Typha angustifolia L., Typha orientalis Presl or other plants of the same genus (Typhaeceae), has effect of activating the circulation to cure blood stasis in traditional Chinese Medicine (TCM). The purpose of this study was to set up an ultra-high performance liquid chromatography method that could determine p-hydroxybenzoic acid and vanillic acid simultaneously in rat plasma, and to compare their pharmacokinetics in normal rats and rats with acute cold blood stasis, and further to investigate the influence of different dosages of oral administration. The pharmacokinetic parameters obtained showed that both the phenolic acids had a higher bioavailability in rats with cold blood stasis than that in normal rats with a higher AUC0-t and longer MRT, and the high dose oral administration group had a higher capacity in blood stasis rats than in normal rats. These results reminded us that changes in health condition could alter the absorption and elimination of both phenolic acids in vivo, and the pharmacokinetic study under pathological conditions provides important information for more rational drug use in clinical situations.
      PubDate: 2017-06-16T17:05:49.321566-05:
      DOI: 10.1002/bmc.4028
  • Determination of the serine palmitoyl transferase inhibitor Myriocin by
           electrospray and Q-trap mass spectrometry
    • Authors: Giuseppe Matteo Campisi; Paola Signorelli, Jessica Rizzo, Claudio Ghilardi, Jacopo Antognetti, Anna Caretti, Jelena S. Lazarevic´, Enrica Strettoi, Elena Novelli, Riccardo Ghidoni, Federico Maria Rubino, Rita Paroni
      Abstract: Myriocin, is a potent inhibitor of serine-palmitoyl-transferase, the first and rate-determining enzyme in the sphingolipids biosynthetic pathway. This study developed, validated and applied a LC-MS/MS method to measure Myriocin in minute specimens of animal tissue. The chemical analog 14-OH-Myriocin is used as the internal standard. The two molecules are extracted from the tissue homogenate by solid-phase extraction, separated by gradient reverse-phase liquid chromatography and measured by negative ion electrospray mass spectrometry in the triple quadrupole. Detection is accomplished by Multiple Reaction Monitoring, employing the most representative transitions: 400@104 and 402@104 for Myriocin and 14-OH-Myriocin, respectively. The typical LoD and LLoQ of the optimized method are 0.9 pmoles/mL (approx. 0.016 pmoles injected) and 2.3 pmoles/mL, respectively, and the method is linear up to 250 pmoles/mL range (r2= 0.9996). The intra-and between-day repeatability affords a CV% ≤ 7.0. Applications included quantification of Myriocin in mouse lungs after 24 hrs from administration of ~4 nmoles by intra-trachea delivery. Measured levels ranged from 4.11 (median; 2.3-7.4 IQR, n=4) to 11.7 (median; 7.6-22.7 IQR, n=6) pmoles/lung depending on the different formulations used. Myriocin was also measured in retinas of mice treated by intravitreal injection and ranged from 0.045 (
      PubDate: 2017-06-16T09:05:19.457172-05:
      DOI: 10.1002/bmc.4026
  • Simultaneous quantification of Imatinib and its main metabolite
           N-demethyl-Imatinib in human plasma by liquid chromatography-tandem mass
           spectrometry and its application to therapeutic drug monitoring in
           patients with gastrointestinal stromal tumor
    • Authors: Wei Zhuang; Hai-bo Qiu, Xin-meng Chen, Xiu-hong Yuan, Li-fang Yang, Xiao-wei Sun, Xiao-jun Zhou, Min Huang, Xue-ding Wang, Zhi-wei Zhou
      Abstract: AimTo improve and validate a more stable and less time-consuming method based on liquid chromatography and tandem mass spectrometry (LC- MS/MS) for the quantitative measurement of Imatinib and its metabolite N-demethyl-Imatinib (NDI) in human plasma.MethodsSeparation of analytes was performed on a Waters XTerra RP18 column (50mm×2.1 mm i.d., 3.5 μm) with a mobile phase consisting of methanol/acetonitrile/ water (65:20:15, v/v/v) with 0.05% formic acid at a flow-rate of 0.2 ml/min. The Quattro MicroTM triple quadruple mass spectrometer was operated in the multiple-reaction monitoring mode via positive electrospray ionization interface using the transition: m/z 494.0 394.0 for Imatinib, m/z 479.6 394.0 for NDI and m/z 488.2 394.0 for IS.ResultsThe method was linear over 0.01–10 μg/mL for Imatinib and NDI. The intra- and inter-day precisions were all less than 15% in terms of relative standard deviation (RSD), and the accuracy was within ±15% in terms of relative error (RE) for both Imatinib and NDI. The lower limit of quantification (LLOQ) was identifiable and reproducible at 10 ng/mL.ConclusionsThe method was sensitive, specific and less time-consuming and it was successfully applied in GIST patients treated with Imatinib.
      PubDate: 2017-06-16T06:30:19.102535-05:
      DOI: 10.1002/bmc.4022
  • Quantitative bioanalysis of bavachalcone in rat plasma by LC-MS/MS and its
           application in a pharmacokinetics study
    • Authors: Dan Zhou; Lianhua An, Yan Xia, Yuanyi Wang, Xingliang Li
      Abstract: This study aims to develop and validate a simple and sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for investigating the pharmacokinetic characteristics of bavachalcone. Liquid-liquid extraction was used to prepare plasma sample. Chromatographic separation of bavachalcone and IS was achieved by using a Venusil ASB C18 (2.1 × 50 mm, 5 μm) column with a mobile phase of methanol (A)–water (B) (70:30, v/v). The detection and quantification of analytes was performed in selected-reaction monitoring mode using precursorproduct ion combinations of m/z 323.1203.2 for bavachalcone, and m/z 373.0179.0 for IS. Linear calibration plots were achieved in the range of 1–1000 ng/mL for bavachalcone (r2> 0.99) in rat plasma. The recovery of bavachalcone ranged from 84.1% to 87.0%. The method showed to be precise, accurate and reliable. It was fully validated and successfully applied to pharmacokinetic study of bavachalcone.
      PubDate: 2017-06-15T12:20:20.823483-05:
      DOI: 10.1002/bmc.4031
  • Enantioselective determination of R-(-)-manidipine and S-(+)-manidipine in
           human plasma by a sensitive and selective chiral LC-MS/MS assay
    • Authors: Vinayender Adireddy; Bhavani Prasanna Kumar Bimireddy, Venkateswarlu Ponneri
      Abstract: A sensitive and selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method has been developed and validated for the enantioselective determination of manidipine in human plasma using isotope labeled compounds as internal standards. After solid phase extraction, R-(-)-manidipine and S-(+)-manidipine were chromatographed on a Chiralpack IC-3 C18 column using a isocratic mobile phase composed of 2mM ammonium bicarbonate and acetonitrile (15:85, v/v). The precursor ion to product ion transitions for the enantiomers and internal standards were monitored in the multiple reaction monitoring and positive ionization mode using a API-4000 mass spectrometer. The method was linear over the concentration range of 0.05-10.2 ng/mL for both the enantiomers. The precision and accuracy results over five concentration levels in five different batches were well within the acceptance limits. The mean extraction recovery was greater than 80% for both the enantiomers. A variety of stability tests were executed in plasma and in neat samples which complies with the FDA guidelines. After complete validation, the method was successfully applied to a pharmacokinetic study of manidipine 20 mg oral dose in 10 healthy South India subjects under fasting conditions. The assay reproducibility is shown through incurred samples reanalysis of 20 subject plasma samples.
      PubDate: 2017-06-15T10:50:27.788362-05:
      DOI: 10.1002/bmc.4027
  • Study of Gliquidone Degradation Behavior by High-Performance Thin-Layer
           Chromatography and Ultra-Performance Liquid Chromatography Methods
    • Authors: Nada S. Abdelwahab; Mohammed T. ELsaady, Aml G. Korany, Maha A. Hegazy
      Abstract: Gliquidone (GQ) is an oral hypoglycemic agent, belongs to second generation sulfonylurea derivatives. New high-performance thin-layer chromatography (HPTLC) and ultra-performance liquid chromatography (UPLC) methods have been developed and validated and used for complete stability study of GQ following ICH guidelines. GQ was subjected to stress and forced degradation under hydrolytic, oxidative and photolytic conditions. The drug was found to be unstable under acidic, alkaline and oxidative conditions with the formation of gliquidone sulfonamide (GQS) while, a marked stability was confirmed under thermal and photolytic stress conditions. GQS is the British pharmacopeial impurity A of GQ and also considered as its synthesis intermediate. The developed chromatographic methods have been utilized for expecting the degradation behavior of GQ under the studied conditions and then used for quantitation of GQ and GQS either in their pure forms or in laboratory prepared mixtures. The methods were successfully applied to GQ in pharmaceutical formulation. The methods have the advantages of being sensitive and less time consuming compared to the reported methods. The obtained results were statistically compared to a reported HPLC method showing no significant difference regarding both accuracy and precision.
      PubDate: 2017-06-15T09:00:29.94565-05:0
      DOI: 10.1002/bmc.4025
  • A platinized stainless steel fiber with in-situ coated
           polyaniline/polypyrrole/graphene oxide nanocomposite sorbent for headspace
           solid-phase microextraction of aliphatic aldehydes in rice samples
    • Authors: Alireza Ghiasvand; Afagh Nasirian, Samira Koonani, Kolsoum Nouriasl
      Abstract: The surface of a stainless steel fiber was made larger, porous and cohesive by platinizing for tightly attachment of its coating. Then, it was coated by a polyaniline/polypyrrole/graphene oxide (PANI/PP/GO) nanocomposite film using electrochemical polymerization (EP) process. The prepared PANI/PP/GO fiber was used for headspace solid-phase microextraction (HS-SPME) of linear aliphatic aldehydes in rice samples followed by gas-chromatography flame ionization detector (GC-FID) determination. To achieve the highest extraction efficiency, various experimental parameters including extraction time and temperature, matrix modifier, and desorption condition were studied. The linear calibration curves were obtained over the range of 0.05-20 μg g-1 (R2>0.99) for C4-C11 aldehydes. The limits of detection (LODs) were found to be in the range of 0.01-0.04 μg g-1. RSDs values were calculated to be lower than 7.4% and 10.7% for intra-day and inter-day, respectively. The superiority of the prepared nanocomposite SPME fiber was established by comparison of its results with those obtained by polydimethylsiloxane (PDMS), carbowax/divinylbenzene (CW/DVB), divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) and polyacrylate (PA) commercial ones. Finally, the nanocomposite fiber was used to extract and determine linear aliphatic aldehydes in eighteen rice samples.
      PubDate: 2017-06-15T08:50:20.613206-05:
      DOI: 10.1002/bmc.4024
  • Severe metabolic impairment with increasing age for CYP3A and CYP2D
           substrates in rats: Possible consequences for drug development
    • Authors: Nuggehally R. Srinivas
      PubDate: 2017-06-07T20:10:21.205229-05:
      DOI: 10.1002/bmc.4009
    • Authors: Ludovit Schreiber; Radoslav Halko, Milan Hutta
      Abstract: Tadalafil is used for the treatment of erectile dysfunction and its related patents expired in 2016, therefore related generic drugs production is supposed to be increased.This work is focused on developing a fast ultra high performance liquid chromatography (UHPLC) with diode array detector (DAD) and/or mass spectrometry (MS) detection for the separation and determination of tadalafil and its impurities in pharmaceutical samples.Modern reversed-phase stationary phase with sub-2 micron particle size, Zorbax StableBond Rapid Resolution High Definition with octylsilane chemically bonded phase to totally porous silica particles was used for the solving this problem. Column temperature was set at 40 ± 0.1 °C. A mobile phase consisting of acetonitrile and aqueous solution of 0.1% (v/v) trifluoroacetic acid for DAD detection and 0.05% (v/v) formic acid, both running at a flow rate of 0.62 mL/min, were used to achieve a required separation of all components within a 5 min run. The limit of detection is 3.5 μg/L and limit of quantification is 10.0 μg/L for the method for both UV and MS detectors. Accurate mass spectra of tadalafil's related impurities are shown for advanced confirmation. The method is directly transferable to routine analysis of tadalafil in pharmaceutical and control laboratories.
      PubDate: 2017-05-30T17:40:23.222624-05:
      DOI: 10.1002/bmc.4020
  • Quantification of morusin using LC–MS in rat plasma: Application to
           a pharmacokinetic study
    • Authors: Zhipeng Deng; Xiaohui Sun, Shenbao Yang, Lei Zhang, Peilu Sun, Xuepeng Teng, Hao Zhong
      Abstract: A sensitive LC–MS method was developed for the quantification of morusin in rat plasma using praeruptorin C as internal standard. After extraction with diethyl ether, post-treatment samples were chromatographed on a Hypersil C18 column. An isocratic mobile phase consisting of methanol-water (70:30, v/v) was applied at a flow rate of 0.4 mL/min. Detection was performed via electrospray ionization source with positive ion mode using selected ion monitoring mode at m/z 443.1 for morusin and m/z 451.0 for IS. Acceptable linearity (r2 ≥ 0.99) was observed over the concentration range of 1.5–800 ng/mL. This method was successfully applied in the pharmacokinetics study of morusin in rats.
      PubDate: 2017-05-30T15:15:24.350735-05:
      DOI: 10.1002/bmc.4021
  • Single-step isolation of embelin using high performance countercurrent
           chromatography and determination of the fatty acid composition of seeds of
           Embelia schimperi
    • Authors: Minaleshewa Atlabachew; Bewketu Mehari, Sandra Combrinck, Robert McCrindle
      Abstract: Embelin(2,5-dihydroxy-3-undecyl-p-benzoquinone)is known for its potent anthelmintic activity, but also for wound-healing, antidiabetic, anticonvulsant, antitumour, anti-inflammatory, analgesic, hepatoprotective, antioxidant, antibacterial andantispermatogenic activities. A high performance countercurrent chromatography method was developed for the purification of embelin from an extract of the seeds of Embelia schimperi fruit. The optimised solvent system (n-hexane:ethylacetate:ethanol:water (7:3:7:3)) resulted in the isolation of 13.9 mg of embelin, directly from 100 mg of crude extract, in a single step within a short retention time (40 min). Although the compound appeared to be completely pure when analysed by ultra performance liquid chromatography (UPLC) with photo diode array detection (PDA), the purity was established as approximately 90% by UPLC-mass spectrometry (MS). Furthermore, we report the fatty acid composition of the seeds of Embelia schimperi fruit. Nine fatty acids were quantified from the fruit seed extract by gas chromatography-mass spectrometry, with linoleic (46.4%), palmitic (21.5%), and oleic (19.6%) acids making up the largest proportions.
      PubDate: 2017-05-30T10:40:38.209601-05:
      DOI: 10.1002/bmc.4018
  • Development of a validated UPLC-MS/MS method for determination of
           humantenmine in rat plasma and its application in pharmacokinetics and
           bioavailability studies
    • Authors: Yanxian Hu; Ming Hao Chen, Zhaoyu Wang, Yao Lan, Lan Tang, Menghua Liu, Jie Zhao, Ming Hu, Lulu Zhang, Ling Ye
      Abstract: Humantenmine (HMT), the most toxic compound isolated from Gelsemium elegans Benth, is a well-known active herbal compound. A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to estimate the absolute oral bioavailability of HMT in rats. Quantification was performed by multiple reaction monitoring using electrospray ionization (ESI) operated in positive ion mode with transitions of m/z 327.14  m/z 296.19 for HMT and m/z 323.20  m/z 236.23 for gelsemine (internal standard, IS). The linear range of the calibration curve was 1-256 nmol/L, with a lower limit of quantification (LLOQ) at 1 nmol/L. The accuracy of HMT ranged from 89.39% to 107.5%, and the precision was within 12.24% (%RSD). Excellent recovery and negligible matrix effect were observed. HMT remained stable during storage, preparation, and analytical procedures. Pharmacokinetics of HMT in rats showed that HMT reached the concentration peak at 12.50 ± 2.74 min with a Cmax of 28.49 ± 6.65 nmol/L, and the corresponding AUC0–t was 1142.42 ± 202.92 nmol/L*min after 200 µg/kg HMT was orally administered to rats. The AUC0–t of HMT given at 20 µg/kg by tail vein administration was 1518.46 ± 192.24 nmol/L*min. The calculated absolute bioavailability of HMT was 7.66%.
      PubDate: 2017-05-30T10:40:37.033491-05:
      DOI: 10.1002/bmc.4017
  • Simultaneous determination of ginsenoside Rb1, ginsenoside Rg1,
           paeoniflorin, albiflorin and oxypaeoniflorin in rat plasma by liquid
           chromatography-tandem mass spectrometry: Application to a pharmacokinetic
           study of Wen-Yang-Huo-Xue soft capsule
    • Authors: Xiujun Wu; Yang You, Gonglin Qu, Ran Ma, Mingxue Zhang
      Abstract: A simple and sensitive HPLC-MS/MS method was developed and fully validated for simultaneous determination of ginsenoside Rb1, ginsenoside Rg1, paeoniflorin, albiflorin and oxypaeoniflorin in rat plasma. Plasma samples were pretreated with protein precipitation using acetonitrile. The chromatographic separation was carried out on a C18 column with a gradient mobile phase consisting of acetonitrile and water (containing 0.1% formic acid). All analytes and digoxin (internal stand, IS) were quantitated through electrospray ionization in negative ion multiple reaction monitoring (MRM) mode. All calibration curves exhibited good linearity (r > 0.9960) over a wide concentration range for all components. The intra-day and inter-day precisions (RSD) at three different levels were all less than 12.0% and the accuracies (RE) ranged from −6.1% to 6.2%. The extraction recoveries of the five compounds ranged from 89.2% to 97.1%. The validated method was successfully applied in comparative pharmacokinetic study of Wen-Yang-Huo-Xue soft capsule (WYHXSC) in rats. Compared with single pure component, the exposure of the investigated components, except for oxypaeoniflorin, increased after oral administration of WYHXSC in rats which suggested the synergistic effects between the herbs in the WYHXSC preparations.
      PubDate: 2017-05-30T09:20:33.297549-05:
      DOI: 10.1002/bmc.4019
  • Metabolic profiling of quercetin in rats using ultra-performance liquid
           chromatography/quadrupole-time-of-flight mass spectrometry
    • Authors: Ming-jiang Wu; Xiao-lei Wu, De-qin Zhang, Feng Qiu, Li-qin Ding, Hao-ling Ma, Xin-ze Chen
      Abstract: Quercetin, a kind of major flavonoid found in many traditional chinese medicines (TCM), is an effective substance for treatment of diseases such as lowering blood lipid. However, the researches on quercetin have been mainly focused on its pharmacological effect, the treatment of diseases on material basis, particularly the metabolites derived from quercetin in vivo has not been evaluated. In this study, we determined the levels, distributions and types of quercetin's metabolites in plasma, urine, feces and bile of rats after a single oral administration of quercetin at a dose of 80 mg/kg, using ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS). A total of 36 metabolites of quercetin were identified, including 11 metabolites in plasma, 34 metabolites in urine, 12 metabolites in feces and 21 metabolites in bile. The results showed that phase I metabolites were reduction metabolites and phase II metabolites mainly included glucuronidation, sulfation and methylation metabolites. These results provide important information on the metabolism of quercetin, which will be helpful for the further development and utilization.
      PubDate: 2017-05-29T14:35:24.107418-05:
      DOI: 10.1002/bmc.4016
  • The human mast cell line-1 cell membrane chromatography coupled with
           HPLC-ESI-MS/MS method for screening potentical anaphylactic components
           from chuanxinlian injection
    • Authors: Yuanyuan Lin; Cheng Wang, Yajing Hou, Huaizhen Hev Limin Huang, Liu Yang, Meng Sun
      Abstract: Chuanxinlian injection is a traditional Chinese medicine injection widely used in China to treat sore throat, cough, and dysentery. While, the high occurrence of severe adverse reactions had been reported in clinical practice in recent years. In the present study, a human mast cell line-1 cell membrane chromatography coupled with HPLC-ESI-MS/MS method was established to screen and identify potentical anaphylactic components in chuanxinlian injection, and the dehydroandrographolide was identified as a potential anaphylactic component. In vitro anaphylactic assay showed that intracellular Ca2+ concentration clearly increased under dehydroandrographolide (100 μM) treatment, β-Hexosaminidase and histamine release in human mast cell line-1 cells were both markedly enhanced with increased concentrations of dehydroandrographolide, confirming the anaphylactic activity of dehydroandrographolide. The application for chuanxinlian injection in this study suggested that the developed human mast cell line-1 cell membrane chromatography coupled with HPLC-ESI-MS/MS system may be effective and rapid for screening the potentical anaphylactic components from complex samples.
      PubDate: 2017-05-29T13:50:24.541815-05:
      DOI: 10.1002/bmc.4015
  • A review of chromatographic methods for Ketamine and its metabolites
           Norketamine and Dehydronorketamine
    • Authors: Eylem Funda GÖKTAŞ; Filiz ARIÖZ
      Abstract: Ketamine has a synthetic, sedative, non-barbiturate and fast-acting anesthetic properties and it is commonly used in both humans and veterinary surgery. There are many analytical methods available for the qualitative and quantitative determination of Ketamine and its metabolites. This review gives information for the implementation of methods to support ketamine and its metabolites studies in researchs and it could be useful in forensic sciences in addition to doping control, human and animal clinical surgery. In this review, we have focused on sample pre-treatment and chromatographic techniques used since 2000 years for the determination of ketamine and its metabolites in biological samples. Liquid and gas chromatography coupled with various detection techniques (mass spectrometry, ultraviolet or fluorescence detection) have been used in these publications. This review gives information for the implementation of methods to support ketamine and its metabolites studies in various research applications. It could be useful in forensic sciences including doping control and also in the therapeutic drug monitoring of ketamine and nor-ketamine in human and animal clinical surgery.
      PubDate: 2017-05-27T01:15:22.178997-05:
      DOI: 10.1002/bmc.4014
  • Comparative pharmacokinetics of acteoside from Total glycoside Extracted
           from Leaves of Rehmannia and Dihuangye total glycoside capsule in normal
           and diabetic nephropathy rats
    • Authors: Xin-xin Dai; Shu-lan Su, Hong-die Cai, Dan-dan Wei, Tian-yao Zheng, Zhen-hua Zhu, Hui Yan, Er-xin Shang, Sheng Guo, Da-wei Qian, Jin-ao Duan
      Abstract: Rehmannia glutinosa Libosch (RG), is officially listed in the Chinese Pharmacopoeia and is widely used in China. In this paper, a sensitive and rapid ultra-performance liquid chromatography-mass spectrometry (UPLC-TQ-MS) including multiple-reaction monitoring mode was developed and applied to study the pharmacokinetics effect of acteoside from Total glycoside Extracted from Leaves of Rehmannia (TLR) and Dihuangye total glycoside capsule (DTG) in normal and diabetic nephropathy rats. Diabetic nephropathy rats model was induced by intraperitoneal injection of a small dose of streptozotocin and high-fat diet and plus 5% glucose drinking water. Samples of plasma of rats were obtained at different time after rats were administrated with TLR (7.2 g/kg) and DTG (360 mg/kg), after the deproteinization by acetonitrile, the concentration of acteoside in rats at different time points were detected by UPLC-TQ-MS method and pharmacokinetics parameters were calculated by DAS 3.2.8 software. A good linearity of acteoside was shown in the ranges of 8.51-3404.8 ng/m L (r2 = 0.9987). The mean extraction recovery of analyte was in the range of 63.55-79.49%, and the intra- and inter-day RSD values were less than 8.8%. Compared with the normal group, the Cmax, AUC0–t, AUC0–∞ and CL/F corresponding dose in model group rats decreased significantly. After rats were administrated with the TLR and DTG, the acteoside reached the maximum plasma concentration was about 15 min. The method is proved to be simple, rapid, and specific, and to be suitable for the determination of acteoside in plasma of diabetic nephropathy rats and the pharmacokinetics study.
      PubDate: 2017-05-23T20:00:23.101527-05:
      DOI: 10.1002/bmc.4013
  • Relationship between the UPLC-Q-TOF-MS fingerprinted constituents from
           Daphne genkwa and their anti-inflammatory, anti-oxidant activities
    • Authors: Wen-Juan Du; Jun Ji, Ling Wang, Xin-Yi Lan, Jia Li, Jun-Qiu Lei, Xin He, Chun-Feng Zhang, Wen-Ze Huang, Zhen-Zhong Wang, Wei Xiao, Chong-Zhi Wang, Chun-Su Yuan
      Abstract: Daphne genkwa Zucc. is a well-known medicinal plant. This study was designed to apply the ultra-high performance liquid chromatography (UPLC) system to establish a quality control method of Daphne genkwa. Data revealed that there were fifteen common peaks in ten batches of D. genkwa Sieb. Et Zucc.(Thymelaeaceae) from different provinces of China. On this basis, the fingerprint chromatogram was established to provide references for quality control. Afterwards, the chemical constitutions of these common peaks were analyzed using the UPLC-Q-TOF-MS system and nine of them were identified primarily. In addition, LPS-stimulated RAW264.7 murine macrophages and DPPH assay were adopted to study the anti-inflammatory and anti-oxidation effects of Daphne Genkwa. Then the fingerprint-efficacy relationship between UPLC fingerprints and pharmacodynamic data were studied with canonical correlation analysis (CCA). Analysis results indicated that the anti-inflammatory and anti-oxidation effects were discrepant among the ten Daphne genkwa samples due to their inherent differences of chemical compositions. Taken together, this research established a fingerprint-efficacy relationship model of Daphne Genkwa plants by combining the UPLC analytic technique and pharmacological researches, which provided references for the detection of the principle components of traditional Chinese medicine on bioactivity.
      PubDate: 2017-05-22T00:55:25.829983-05:
      DOI: 10.1002/bmc.4012
  • Hydrophilic interaction and reversed-phase ultra-performance liquid
           chromatography TOF-MS for metabolomic analysis of Veratrum nigrum-induced
    • Authors: Ziheng Wei; Xu Dong, Hanzhe Zhang, Songyan Gao, Wei Shi, Feng Yang, Xin Dong
      Abstract: The acute cardiotoxicity induced by Veratrum nigrum (VN) is explored by analysing heart tissue metabolic profiles in mouse models and applying reversed-phase liquid chromatography mass spectrometry (RPLC-MS) and hydrophilic interaction liquid chromatography mass spectrometry (HILIC-MS) that are based on ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). An animal model of acute heart injury was established in mice via intra-gastric administration of VN. Then, electrocardiogram, echocardiograph monitoring of cardiac function and pathological examination were performed on mice both in the control and VN groups, and it was successfully verified that acute heart injury was caused. Meanwhile, comparing the results of the control and VN groups, we detected 36 differential endogenous metabolites of heart tissue, including taurine, riboflavin, purine and lipids, etc., which are related to many possible pathways such as purine metabolism, taurine and hypotaurine metabolism and energy metabolism. Our study provides a scientific approach for evaluating and revealing the mechanisms of VN-induced cardiotoxicity via the metabolomic strategy.
      PubDate: 2017-05-22T00:35:23.930359-05:
      DOI: 10.1002/bmc.4011
  • Development and validation of an LC-ESI-MS/MS approach to determinate a
           highly hydrophobic drug, Norcantharidin Palmitate, and apply to a
           preliminary pharmacokinetic study in rats
    • Authors: Xiaolin Liu; Xiaoguang Tao, Qi Zheng, Hang Xu, Yu Zhang, Tian Lei, Tian Yin, Haibing He, Xing Tang
      Abstract: In order to investigate the pharmacokinetics of norcantharidin palmitate (NCTD-PAL) in rats, we developed and validated an LC-ESI-MS/MS method. The NCTD-PAL and internal standard (Triamcinoloneacetonide palmitate, TAP) were separated on a Phenomenex Kinetex®XB C18 column, and the mobile phase was composed of tetrahydrofuran (THF)-acetonitrile (20/80, v/v) and an aqueous phase containing 0.2% ammonium hydroxide at a flow rate of 0.3 mL/min. The ESI interface operated in positive mode was used to acquire the mass spectrometric data, and the transition ions were m/z 635.50 168.95 and 673.65 397.13 for NCTD-PAL and IS, respectively. The method had a linear range of 10-2,000 ng/mL with correlation coefficient of more than 0.99. The accuracy (RE, %) was within ±10.1%, and the intra-day and inter-day precisions (RSD, %) were 10.9% < and 13.8%, respectively. The extraction recovery of NCTD-PAL at different concentrations ranged from 89.3% to 102.0%. The validated approach was efficaciously applied to a pharmacokinetic study of NCTD-PAL in rats via intravenous injection. Based on these results obtained, this method is practical and is suitable for a wide range of applications.
      PubDate: 2017-05-12T23:49:01.781218-05:
      DOI: 10.1002/bmc.4010
  • Structural identification of degradants of moexipril by LC-MS/MS
    • Authors: C. Purushotham Reddy; K. Ramakrishna, K. M. V. Narayana Rao
      Abstract: A gradient LC-MS method was developed for the identification and characterization of degradants of moexipril using liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). Moexipril was subjected to hydrolysis (acid, base and neutral), oxidation, photolytic and thermal degradation conditions as mentioned in ICH guidelines Q1A (R2). The drug degraded under hydrolysis, oxidation and photolytic conditions, but it was stable under thermal conditions. In total, five degradants were formed and separated on an Agilent XDB C-18 column (4.6 X 150 mm, 5 µm) in a gradient elution method. Four degradants (D1, D2, D4 and D5) under acidic conditions, three degradants (D2, D3 and D4) under basic conditions and three degradants (D1, D4 and D5) under neutral and oxidative stress conditions were formed. In addition, two degradants (D4 and D5) were formed under photolytic stress conditions. To elucidate the structures of degradants, fragmentation of moexipril and its degradants was studied by using LC-MS/MS experiments and accurate mass measurements (HRMS) data. The fragment ions in the product ion tandem mass spectra of all the degradants were compared with those of moexipril and assigned the probable structures for the degradants.
      PubDate: 2017-05-10T22:15:37.872944-05:
      DOI: 10.1002/bmc.4004
  • Suitability of selected chromatographic columns for analysis of fatty
           acids in dialyzed patients
    • Authors: Magdalena Pazda; Piotr Stepnowski, Tomasz Sledzinski, Michal Chmielewski, Adriana Mika
      Abstract: Gas chromatography-mass spectrometry (GC-MS) is a preferred method for fatty acid (FA) analysis in biofluids from patients with metabolic diseases. Complex characteristics of FAs make their analysis particularly challenging. Selection of an appropriate chromatographic column is particularly important component of the process as it provides optimal separation and detection of possibly all FAs present in the sample. However, no accurate protocol for comparative evaluation of capillary columns for the analysis of whole serum FA profile in patients with chronic kidney disease (CKD) has been developed thus far. Therefore, in present study four columns were examined to select the one providing optimal separation and determination of FA profiles in this group of patients. Moreover, serum FA profiles obtained with the selected column in CKD patients subjected to peritoneal dialysis and healthy controls were compared. 37 Component FAME Mix and sera from CKD patients were used to optimize chromatographic conditions and to select the most appropriate column. ZB-5 column turned out to be the most appropriate for the analysis of whole FA profile in CKD patients’ sera. Then, this column was used to compare FA profiles in patients subjected to peritoneal dialysis and in healthy controls. The analysis demonstrated many abnormalities in the FA profile of CKD patients. Further studies involving larger groups of patients presenting with other stages of CKD are required to explain the impact of the disease progression on composition of serum FAs.
      PubDate: 2017-05-10T22:15:34.528359-05:
      DOI: 10.1002/bmc.4006
  • UHPLC-ESI-MS/MS determination and pharmacokinetics of pinoresinol
           glucoside and chlorogenic acid in rat plasma after oral administration of
           Eucommia ulmoides Oliv extract
    • Authors: Xiaojian Gong; Qingxiang Luan, Xin Zhou, Yang Zhao, Chao Zhao
      Abstract: This study aimed to develop a specific UHPLC-ESI-MS/MS method for simultaneous determination and pharmacokinetics of pinoresinol glucoside and chlorogenic acid in rat plasma after oral administration of E. ulmoides. The chromatographic separation was achieved on a Hypersil GOLD column with gradient elution by using a mixture of 0.1% formic acid aqueous solution and acetonitrile as the mobile phase at a flow rate of 200 μL/min. A tandem mass spectrometric detection was conducted using multiple-reaction monitoring (MRM) via an electrospray ionization (ESI) source in negative ionization mode. Samples were pre-treated by a single-step protein precipitation with acetonitrile, and bergenin was used as internal standard (IS). After oral administration of 3 mL/kg E. ulmoides extract in rats, the maximum plasma concentration (Cmax) of pinoresinol glucoside, chlorogenic acid were 57.44 and 61.04 ng/mL, respectively. The time to reach the maximum plasma concentration (Tmax) were 40.00 and 23.33 min for pinoresinol glucoside and chlorogenic acid, respectively. The intra-day and inter-day precision (RSD%) values for the two analytes were less than 2.46% and 5.15%, respectively, and the accuracy (RE%) values ranged from -12.76 to 0.00. This is the first study on pharmacokinetics of bioactive compounds in rat plasma after oral administration of E. ulmoides extract.
      PubDate: 2017-05-10T22:15:32.040265-05:
      DOI: 10.1002/bmc.4008
  • Development and validation of HPLC-MS/MS method for the determination of
    • Authors: Adnan A. Khady; Haithem Alrabiah, Mohamed W. Attwa, Sabray Attia, Gamal A. E. Mostafa
      Abstract: The aim of the present study was to develop a simple, sensitive, and accurate liquid chromatography-electrospray ionization tandem mass spectrometry (ESI-MS/MS) method for the determination of lixivaptan (LIX) in mouse plasma by using vildagliptin as the internal standard (IS). A precipitation procedure was used for the extraction of LIX and vildagliptin from mouse plasma. Chromatographic separation of LIX was achieved using a C18 analytical column (50 mm × 2.1 mm, 1.8 µm) at 25 °C. The mobile phase comprised of acetonitrile and ammonium formate (10 mM, pH 3.1) (40:60, v/v) pumped at a flow rate of 0.3 mL min-1. A tandem mass spectrometer with an electrospray ionization source was used to perform the assay. Quantification of LIX at m/z 290  137 and IS at 154  97 was attained through MRM. The investigated method was authenticated following the bio-analytical method of validation guidelines of FDA. The developed method showed a good linearity over the concentration range from 5 - 500 ng mL-1, and the calibration curve was linear (r = 0.9998). The mean recovery of LIX from mouse plasma was 99.2 ± 0.68 %. All validation parameters for lixivaptan were within the levels required for acceptance. The proposed method was effectively used for a pharmacokinetic study of LIX in mouse plasma.
      PubDate: 2017-05-10T22:15:26.533961-05:
      DOI: 10.1002/bmc.4007
  • Development and validation of a sensitive UHPLC-MS/MS method for
           quantitative analysis of farrerol in rat plasma: Application to
           pharmacokinetic and bioavailability studies
    • Authors: Li Piao; Mingcui Zang, Yue Gu, Baohua Liu
      Abstract: Farrerol is a 2,3-dihydro-flavonoid isolated from rhododendron. In this study, a sensitive and selective ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the determination of farrerol in rat plasma. Liquid-liquid extraction by ethyl ether was used for sample preparation. Chromatographic separation was achieved on an Agilent UHPLC XDB-C18 column (2.1 mm × 100 mm, 1.8 µm) with water and methanol (30:70, v/v) as the mobile phase. An electrospray source was applied and operated in negative ion mode; selection reaction monitoring was used for quantification using target fragment ions m/z 299  179 for farrerol and m/z 267  252 for internal standard. Calibration plots were linear in the range of 2.88–1440 ng/mL for farrerol in rat plasma. Intra-day and inter-day precisions were less than 11.6%, and the accuracy ranged from –13.9% to 11.9%. The UHPLC-MS/MS method was successfully applied in pharmacokinetics and bioavailability studies of farrerol in rats.
      PubDate: 2017-05-10T22:10:22.534808-05:
      DOI: 10.1002/bmc.4005
  • Fast and Parallel determination of PCB 77 and PCB 180 in plasma using
           Ultra Performance Liquid Chromatography (UPLC) with diode array detection
           (DAD): A Pharmacokinetic study in Swiss albino mouse
    • Authors: N. Ramanujam; M. Sivaselvakumar, S. Ramalingam
      Abstract: A simple, sensitive and reproducible ultra-performance liquid chromatography (UPLC) method has been developed and validated for simultaneous estimation of PCB 77 and PCB 180 in mouse plasma. The sample preparation was performed by simple liquid-liquid extraction technique. The analytes were chromatographed on a Waters Acquity H class UPLC system using isocratic mobile phase conditions at a flow rate of 0.3 mL/min and Acquity UPLC BEH shield RP18 column maintained at 35 °C temperature. Quantification was performed on a photodiode array detector set at 215 nm and PCB 101 was used as internal standard (IS). PCB 77, PCB 180, and IS retention times were found to be 2.6, 4.7 and 2.8 min, respectively, and the total run time was 6 min. The method was validated for specificity, selectivity, recovery, linearity, accuracy, precision, and sample stability. The calibration curve was linear over the concentration range 10 to 3000 ng/mL for PCB 77, and PCB 180. Intra- and inter-day precisions for PCBs 77 and 180 were found to be good with % CV
      PubDate: 2017-05-08T20:30:25.570772-05:
      DOI: 10.1002/bmc.4000
  • Development and validation of a liquid chromatography tandem mass
           spectrometry method for the measurement of urinary catecholamines in
           diagnosis of pheochromocytoma
    • Authors: Ying Shen; Liming Cheng, Qing Guan, Huijun Li, Jie Lu, Xu Wang
      Abstract: The measurement of catecholamines in human body fluids is requested frequently for the differential diagnosis and monitoring of pheochromocytoma. The methods in most clinical laboratories focus on high performance liquid chromatography coupled with electrochemical detection which suffers from high background noise, low sensitivity, and poor separation. We reported and developed a robust high-throughput liquid chromatography tandem mass spectrometry method in routine clinical laboratories for the measurement of urinary catecholamines for diagnosis of pheochromocytoma.The method was validated for consistent linearity, good recovery (88%-112%), excellent stability and low carryover. Intra-assay and inter-assay imprecision values for catecholamines were all below 3.35% and 4.83% respectively. Dilution linearity was investigated with satisfied linearly dependent coefficients (r > 0.9988). The reference intervals were obtained from 310 results derived from patients in which the diagnosis of pheochromocytoma was excluded. This method was successfully used in our lab. The clinical characteristics of patients have been explored with satisfied sensitivity and specificity. Therefore, we have developed a reliable assay for the liquid chromatography tandem mass spectrometry measurement of catecholamines in a routine clinical laboratory. The assay requires a small volume of urine, and all analytes are measured simultaneously. The assay is rapid and reliable to execute offering the potential for routine clinical laboratories.
      PubDate: 2017-05-08T09:40:25.915065-05:
      DOI: 10.1002/bmc.4003
  • Screening free radical scavengers in Xiexin Tang by HPLC-ABTS-DAD-Q-TOF/MS
    • Authors: Yu-Qing Wang; Shu-Jiao Li, Guo Zhuang, Rong-Hui Geng, Xu Jiang
      Abstract: Xiexin Tang (XXT) is a traditional Chinese medicine (TCM) that has been used in herbal clinics for more than 1800 years. Many studies have shown that XXT has therapeutic effects on patients with arteriosclerosis (AS) owing to its antioxidant activity. However, there is little information about the relationship between the chemical composition of XXT and its antioxidant activity. In this study, the HPLC-ABTS-DAD-Q-TOF/MS method, which can simultaneously identify individual components and rapidly screen for antioxidant compounds, was used to screen and identify antioxidant components in XXT. The fifteen compounds identified were gluco-syringic acid, adenine, gallic acid, biflorin, cularine, 6-C-arabinose-8-C-glucose-chrysin, 6-C-glucose-8-C-arabinose–chrysin, baicalin, rhein-8-O-β-D-glucopyranoside, coptisine, epiberberine, jatrorrhizine, norwogonin, 5,7,2'-trihydroxy-6- methoxyflavone, and baicalein. In addition, the data showed that the antioxidant activity of peaks 4, 6, and 11 was lower in XXT than in its constituent herbs, while the activity of peaks 1, 2, 3, 5, 7, 8, 10, 12, 13, 14, and 15 was higher in XXT. Compound 5 had the strongest antioxidant activity in XXT, while compound 1 showed the strongest antioxidant activity among its constituent herb. The differences between antioxidant activity of major components of XXT and its constituent herbs might be due to the interaction of crude drugs that changes the solubility of active components during the decoction process. The results show that the HPLC-ABTS-DAD-Q-TOF/MS method can successfully combine on-line mass spectrometry with activity detection system. It is a useful tool for the rapid detection and identification of antioxidants, and for quantitative analysis of individual antioxidants in complex mixtures such as plant extracts. Furthermore, this method does not require extensive extract purification and fraction collection.
      PubDate: 2017-05-06T02:05:33.324831-05:
      DOI: 10.1002/bmc.4002
  • Identification of differential metabolic characteristics between tumor and
           normal tissue from colorectal cancer patients by gas chromatography-mass
    • Authors: Wu Ning; Haijing Li, Fanqiang Meng, Jianhua Cheng, Xin Song, Guochao Zhang, Wenyue Wang, Shengming Wu, Junjian Fang, Kunpeng Ma, Jie Yang, Dongpo Pei, Fangting Dong
      Abstract: Colorectal cancer (CRC) is one of the most common human malignancies and encompasses cancers of the colon and rectum. Although the gold-standard colonoscopy screening method is effective in detecting CRC, this method is invasive and can result in severe complications for patients. The purpose of this study was to determine differences in metabolites between CRC and matched adjacent non-tumor tissues from CRC patients, to identify potential biomarkers that may be informative and developed screening methods. Metabolomic analysis was performed on clinically localized CRC tissue and matched adjacent non-tumor tissue from twenty CRC patients. Unsupervised analysis, supervised analysis, univariate analysis, and pathway analysis were used to identify potential metabolic biomarkers of CRC. The level of twenty-five metabolites in CRC tissues were significantly altered compared to the matched adjacent non-tumor tissues. Four metabolites (lactic acid, alanine, phosphate, and aspartic acid) demonstrated good area under the curve (AUC) of Receiver- Operator Characteristic (ROC) with acceptable sensitivities and specificities, indicating their potential as important biomarkers for CRC. Alterations of amino acid metabolism and enhanced glycolysis may be major factors in the development and progression of colorectal cancer. Lactic acid, alanine, phosphate, and aspartic acid could be effective diagnostic indicators for CRC.
      PubDate: 2017-05-05T08:20:41.549457-05:
      DOI: 10.1002/bmc.3999
  • A simple LC-MS/MS method facilitated by salting-out assisted
           liquid–liquid extraction (SALLE) to simultaneously determine
           trans-resveratrol (Res), its glucuronide and sulfate conjugates in rat
           plasma and its application to pharmacokinetic assay
    • Authors: Zhixia Qiu; Jiaojiao Yu, Yu Dai, Yue Yang, Xiaoyu Lu, Jiaqiu Xu, Zhiying Qin, Fang Huang, Ning Li
      Abstract: A simple LC-MS/MS method facilitated by salting-out assisted liquid–liquid extraction (SALLE) was applied to simultaneously investigate pharmacokinetics of trans-resveratrol (Res), its major glucuronide and sulfate conjugates in rat plasma. Acetonitrile-methanol (80:20, v/v) and ammonium acetate (10 mol∙L-1) were used as extractant and salting-out reagent to locate the target analytes in the supernatant after the aqueous and organic phase stratification, then the analytes were determined via gradient elution by LC-MS/MS in negative mode in a single run. The analytical method was validated with good selectivity, acceptable accuracy (above 85%) and low variation of precision (below 15%). SALLE showed better extraction efficiency of target glucuronide and sulfate conjugates (>80%). The method was successfully applied to determine Res and its four conjugated metabolites in rat after Res administration (intragastric, 50 mg/kg; intravenous, 10 mg/kg). The systemic exposures to Res conjugates were much higher than Res (AUC0-t, i.v, 7.43 μM∙h; p.o, 8.31 μM∙h), Res-3-O-β-D-Glucuronide was the major metabolite (AUC0-t, i.v, 66.1 μM∙h; p.o, 333.4 μM∙h). The bioavailability of Res was estimated around 22.4%. The reproducible SALLE method simplified the sample preparation, drastically improved the accuracy of the concomitant assay and gave full consideration of extraction recovery to each target analyte in bio-samples.
      PubDate: 2017-05-05T07:51:07.033743-05:
      DOI: 10.1002/bmc.4001
  • A comparative pharmacokinetic study of three flavonoids and three
           anthraquinones in normal and gastrointestinal motility disorders rat
           plasma after the oral administration of Wei-Chang-Shu tablet using
           high-performance liquid chromatography-tandem mass spectrometry
    • Authors: Yan Ren; Weiwei Zhao, Juanjuan Zhao, Xiangming Chen, Chen Yu, Mengan Liu
      Abstract: A simple, fast and reliable high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification and pharmacokinetic study of three flavonoids (liquiritigenin, isoliquiritigenin and formononetin) and three anthraquinones (emodin, rhein and aloe-emodin), which are the bioactive ingredients of Wei-Chang-Shu tablet found in rat plasma. After extraction by liquid-liquid extraction with ethyl acetate, chromatographic separation was achieved on an Agilent ZORBAX SB-C18 column (4.6 mm × 150 mm, 5 µm) at a flow rate of 1 mL/min by gradient elution using 0.1% aqueous acetic acid and acetonitrile. The detection was performed using a triple quadrupole mass spectrometer equipped with electrospray ionization source in the negative ionization and selected reaction monitoring mode. Method validation was performed in terms of specificity, carryover, linearity (r > 0.99), intra-/inter-day precision (1.0-10.1%), accuracy (relative error,
      PubDate: 2017-05-05T04:52:47.502272-05:
      DOI: 10.1002/bmc.3997
  • A simple and sensitive high-performance liquid chromatography-
           electrochemical detection assay for the quantitative determination of
           monoamines and respective metabolites in six discrete brain regions of
    • Authors: Serena A. Allen; Stephanie Rednour, Samantha Shepard, Brooks Barnes Pond
      Abstract: A rapid, sensitive, and reproducible assay is described for the quantitative determination of the monoamine neurotransmitters dopamine, norepinephrine, and serotonin, their metabolites, and the internal standard 3,4- dihydroxybenzlyamine hydro-bromide (DHBA) in mouse brain homogenate using high performance liquid chromatography with electrochemical detection. The method was validated in the following brain areas: frontal cortex, striatum, nucleus accumbens, hippocampus, substantia nigra pars compacta, and ventral tegmental area. Biogenic amines and relevant metabolites were extracted from discrete brain regions using a simple protein precipitation procedure, and the chromatography was achieved using a C18 column. The method was accurate over the linear range of 0.300 – 30 ng/mL (r = 0.999) for dopamine and 0.300 – 15 ng/mL (r = 0.999) for norepinephrine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindolacetic acid, with detection limits of approximately 0.125 ng/mL (5 pg on column) for each of these analytes. Accuracy and linearity for serotonin was observed throughout the concentration range of 0.625 – 30 ng/mL (r = 0.998) with an analytical detection limit of approximately 0.300 ng/mL (12 pg on column). Relative recoveries for all analytes were approximately ≥ 90% and the analytical run time was less than 10 min. The described method utilized minimal sample preparation procedures and was optimized to provide the sensitivity limits required for simultaneous monoamine and metabolite analysis in small, discrete brain tissue samples.
      PubDate: 2017-05-05T04:17:15.425172-05:
      DOI: 10.1002/bmc.3998
  • Analysis of toldimfos in porcine muscle and bovine milk using liquid
           chromatography–triple quadrupole mass spectrometry
    • Authors: Dan Zhang; Jin-A Park, A. M. Abd El-Aty, Seong-Kwan Kim, Sang-Hyun Cho, Weijia Zheng, Jeong-min Choi, Jae-Han Shim, Byung-Joon Chang, Jin-Suk Kim, Ho-Chul Shin
      Abstract: An analytical method was developed for the detection of toldimfos sodium residues in porcine muscle and bovine milk using liquid chromatography–triple quadrupole tandem mass spectrometry (LC-MS/MS) analysis. The drug was extracted from muscle and milk using 10 mM ammonium formate in acetonitrile and then purified using n-hexane. The drug was well separated on a Luna C18 column using a mixture of 10 mM ammonium formate in ultrapure water (A) and acetonitrile (B) as the mobile phase. Good linearity was achieved over the tested concentration range (0.005 – 0.03 mg/kg) in matrix-matched standard calibration. The determination coefficients (R2) were 0.9942 and 0.9898 for muscle and milk, respectively. Fortified porcine muscle and bovine milk contained concentrations equivalent to and twice the limit of quantification (LOQ = 0.005 mg/kg) yield recoveries in the range of 75.58 – 89.74% and relative standard deviations (RSDs) of ≤ 8.87%. Samples collected from large markets located in Seoul, Republic of Korea, tested negative for toldimfos sodium residue. In conclusion, ammonium formate in acetonitrile can effectively extract toldimfos sodium from porcine muscle and bovine milk without solid-phase extraction, which is usually required for cleanup before analysis. This method can be applied for the routine analysis of toldimfos in foods of animal origins.
      PubDate: 2017-04-27T13:24:19.308045-05:
      DOI: 10.1002/bmc.3996
  • An HPLC method for simultaneous quantitative determination of seven
           secoiridoid glucosides separated from the roots of Ilex pubescens
    • Authors: Yang Zhang; Huan Xiong, Jiayi Bi, Guiyun Zhao, Yi Yang, Xue Chen, Yuncong Li, Chongyu Zhang, Guogang Zhang
      Abstract: A simple and specific high-performance liquid chromatographic method has been developed and validated to simultaneously determine seven secoiridoid glucosides for the first time. And three of them were separated from the ethanolic extract of the roots of Ilex pubescens for the first time, namely nuezhenide A, ligusides B and oleonuezhenide. In quantitative analysis, all of the calibration curves showed good linear regression (r > 0.999) within the tested ranges, and the mean recoveries of three different concentrations ranged from 97.6 ~ 101.2%. The limit of detection and limit of quantification were lower than 4.18 and 11.63 ng/mL, respectively. The relative standard deviation for repeatability and the precision of seven analytes were less than 3.4% and 1.9%. The established method was successfully applied to simultaneous determination of seven secoiridoid glucosides in 11 batches of samples collected from different habitats in China.
      PubDate: 2017-04-25T10:30:35.098692-05:
      DOI: 10.1002/bmc.3995
  • A novel mass spectrometry–based method for simultaneous determination of
           asymmetric and symmetric dimethylarginine, L-arginine, and L-citrulline
           optimized for LC-MS-TOF and LC-MS/MS
    • Authors: Jerzy Wiśniewski; Mariusz G. Fleszar, Joanna Piechowicz, Małgorzata Krzystek-Korpacka, Angelika Chachaj, Andrzej Szuba, Katarzyna Lorenc-Kukula, Leszek Masłowski, Wojciech Witkiewicz, Andrzej Gamian
      Abstract: Nitric oxide (NO) is a regulatory molecule involved in many biological processes. NO is produced by nitric oxide synthase by conversion of L-arginine to L-citrulline. L-arginine methylated derivatives, asymmetric and symmetric dimethylarginines (ADMA and SDMA), regulate L-arginine availability and the activity of nitric oxide synthase. As such, they have been frequently investigated as potential biomarkers in pathologies associated with dysfunctions in NO synthesis. Here, we present a new multistep analytical methodology based on liquid chromatography combined with mass spectrometry for the accurate identification of L-arginine, L-citrulline, ADMA, and SDMA. Compounds are measured as stable 2,3,4,5,6-pentafluorobenzoyl chloride derivatives, which allows for simultaneous analysis of all compounds through chromatographic separation of ADMA and SDMA using a reverse phase column. Serum aliquots (100 μL) were spiked with isotope-labeled internal standards and sodium carbonate buffer. The derivatization process was carried out at 25 °C for 10 minutes using pentafluorobenzoyl chloride as derivatization reagent. Calibration demonstrated good linearity (R2 = 0.9966-0.9986) for all derivatized compounds. Good accuracy (94.67–99.91%) and precision (1.92–11.8%) were observed for the quality control samples. The applicability of the method was evaluated in a cohort of angiological patients and healthy volunteers. The method discerned significantly lower L-arginine, L-citrulline in angiologic patients. This robust and fast LC-ESI-MS method may be a useful tool in quantitative analysis of L-arginine, ADMA, SDMA and L-citrulline.
      PubDate: 2017-04-24T00:45:34.810786-05:
      DOI: 10.1002/bmc.3994
  • Therapeutic drug monitoring of Mitotane: analytical assay and patient
    • Authors: Catherine Feliu; Yoann Cazaubon, Helene Guillemin, Damien Vautier, Olivier Oget, Hervé Millart, Claire Gozalo, Zoubir Djerada
      Abstract: BackgroundAdrenocortical carcinoma (ACC) is an aggressive malignancy of the adrenal gland. Mitotane (o,p′-DDD) is the most effective chemotherapy for ACC. According to literature, mitotane plasma trough concentrations within 14-20 mg.L1 are correlated with a higher response rate with acceptable toxicity. Therapeutic drug monitoring (TDM) of mitotane is therefore recommended. The aim of this study was to propose a robust, and simple method for mitotane quantification in plasma. The validation procedures were based on international guidelines.MethodsSample preparation consisted in a single protein precipitation with methanol using 100 μL of plasma. The supernatant was submitted to liquid chromatography coupled with ultra-violet detection at 230 nm.ResultsMitotane retention time was 7.1 minutes. Limit of detection was 0.1 mg.L-1 and limit of quantification was 0.78 mg.L-1. The assay demonstrated a linear range of 0.78 to 25 mg.L-1 with correlation coefficients (r2) at 0.999. Inter- and intra-assay precision were less than 4.85 %. Evaluation of accuracy showed a deviation less than 13.69 % from target concentration at each quality control level.ConclusionThis method proved easy and rapid to perform mitotane TDM and required a small volume of sample. It was successfully applied to routine TDM in our laboratory.
      PubDate: 2017-04-22T08:26:31.738109-05:
      DOI: 10.1002/bmc.3993
  • UHPLC-Q-TOF-MS/MS based screening and characterization of metabolites of
           cnidilin in human liver microsomes
    • Authors: Lin Yuan; Yuqian Zhang, Man Liao, Yanyan Liu, Changchen Wan, Lantong Zhang
      Abstract: Cnidilin is an active natural furocoumarin ingredient originating from well-known traditional Chinese medicine Radix Angelicae dahuricae. In the present study, an efficient approach was developed for the screening and identification of cnidilin metabolites using ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. In this approach, an on-line data acquisition method multiple mass defect filter (MMDF) combined with dynamic background subtraction was developed to trace all probable metabolites. Based on this analytical strategy, a total of 24 metabolites of cnidilin were detected in human liver microsomal incubation samples and the metabolic pathways were proposed. The results indicated that oxidation was the main biotransformation route for cnidilin in human liver microsomes (HLM). In addition, the specific cytochrome P450 (CYP) enzymes involved in the metabolism of cnidilin were identified using chemical inhibition and CYP recombinant enzymes. The results showed that CYP1A2 and CYP3A4 might be the major enzymes involved in the metabolism of cnidilin in HLM. The relationship between cnidilin and the CYP450 enzymes could provide us a theoretical basis of the pharmacological mechanism.
      PubDate: 2017-04-21T17:06:19.950012-05:
      DOI: 10.1002/bmc.3992
  • Carboxymethyl β-cyclodextrin as chiral selector in capillary
           electrophoresis: enantioseparation of 16 basic chiral drugs and its chiral
           recognition mechanism associated with drugs’ structural features
    • Authors: Linlin Fang; Yueying Du, Xiaoyu Hu, Linda Luo, Xin Guo, Xingjie Guo, Jia Yu
      Abstract: Herein we present the enantioseparation of 10 cardiovascular agents and 6 bronchiectasis drugs including propranolol, carteolol, metoprolol, atenolol, pindolol, esmolol, bisoprolol, bevantolol, arotinolol, sotalol, clenbuterol, procaterol, bambuterol, tranterol, salbutamol and terbutaline sulfate using carboxymethyl-β-cyclodextrin (CM-β-CD) as chiral selector. To our knowledge, there is no literature about using CM-β-CD for separating carteolol, esmolol, bisoprolol, bevantolol, arotinolol, procaterol, bambuterol and tranterol. During the course of work, changes in pH, CM-β-CD concentration, buffer type and concentration were studied in relation to chiral resolution. Excellent enantiomeric separations were obtained for all 16 compounds, especially for procaterol, impressive resolution value, up to 17.10 was obtained. Particularly, most of them were achieved rapid separations within 20 minutes. Given the fact that enantioseparation results rely on analytes’ structural characters, the possible separation mechanisms were discussed. Besides, in order to obtain faster separation for propranolol enantiomers in practical application, the effective length of capillary was innovatively shortened from 45 cm to 30 cm. After the validation, the method was successfully applied to the enantiomeric purity determination of propranolol in the formulation of drug substances.
      PubDate: 2017-04-21T17:01:40.831238-05:
      DOI: 10.1002/bmc.3991
  • Simultaneous quantification and semi-quantification of Amentoflavone and
           its metabolites in human intestinal bacteria by liquid chromatography
           Orbitrap high resolution mass spectrometry
    • Authors: Yiyun Qian; Shu Jiang, Zhenhua Zhu, Qi Wang, Shulan Su, Jinhua Tao, Jin-ao Duan
      Abstract: A quick, easy, effective method followed by ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap MS) was developed for the simultaneous identification and quantification of the metabolites produced by Amentoflavone (AMF) in human intestinal bacteria from human feces. The method validated for quantification of AMF concerning precision, accuracy, recovery, matrix effect, stability and limits showed acceptable results. Compared the blank human intestinal bacteria chromatography, three metabolites were presumed based on high-accuracy protonated precursors and multi-stage mass spectrometry (MSn) using the proposed strategy. At the same time, a new method was developed for semi-quantification of three metabolites. In 24 h, we described the trend of concentration-time curves of the AMF and its metabolites. Moreover, the main metabolic pathway of the AMF was clarified in human intestinal bacteria. The method was validated and successfully applied to detection and quantification of AMF and its metabolites.
      PubDate: 2017-04-20T16:07:21.336991-05:
      DOI: 10.1002/bmc.3990
  • Validated UHPLC-MS/MS assay for quantitative determination of etoposide,
           gemcitabine, vinorelbine and their metabolites in lung cancer patients
    • Authors: Xiaobin Gong; Le Yang, Feng Zhang, Youtian Liang, Shouhong Gao, Ke Liu, Wansheng Chen
      Abstract: A fully valid ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC- MS/MS) method was developed for the determination of etoposide, gemcitabine, vinorelbine and their metabolites (etoposide catechol, 2’,2’-difluorodeoxyuridine and 4-O-deacetylvinorelbine) in human plasma. Multiple reaction monitoring (MRM) mode was performed with an electrospray ionization (ESI) interface operating in both the positive and negative ion modes per compound. The method required only 100 μL plasma with a one-step simple de-proteinization procedure, and a short run time of 7.5 min per sample. A Waters ACQUITY UPLC HSS T3 column (2.1 × 100 mm, 1.8 µm) provided chromatographic separation of analytes using a binary mobile phase gradient (A, 0.1% formic acid in acetonitrile, v/v; B, 0.1% formic acid in water, v/v). Linear coefficients of correlation were >0.995 for all analytes. The relative deviation of this method was
      PubDate: 2017-04-13T17:15:43.207767-05:
      DOI: 10.1002/bmc.3989
  • Retention of glycopeptides analyzed using hydrophilic interaction
           chromatography is influenced by charge and carbon chain length of
           ion-pairing reagent for mobile phase
    • Authors: Kenichiro Furuki; Toshimasa Toyo'oka
      Abstract: Characterization of the glycans of glycoproteins is essential for the development and production of biologics. Numerous methods are available for analyzing the glycans of glycoproteins directly and labeled glycans. Nevertheless, glycopeptides are difficult to resolve because of their exceptional complexity and the microheterogeneity of glycans. These properties represent technical challenges to efforts to insure the accurate characterization of biopharmaceuticals to comply with regulatory requirements. Therefore, we investigated the retention behavior of peptides and glycopeptides in hydrophilic interaction chromatography (HILIC)-mode HPLC in the presence of ion-pairing reagents. Anionic ion-pairing reagents decreased the retention times of glycopeptides and improved resolution in the presence of higher concentrations or hydrophobicities of ion-pairing reagent. Anionic ion-pairing reagents increased retention times of larger glycans because of their increased hydrophilicity. In contrast, in the presence of cationic ion-pairing reagents, the retention times of glycopeptides with greater numbers of sialic acid residues decreased. It is appropriate to add an anionic ion-pairing reagent to the mobile phase for good separation of glycopeptides. The collision cross-sectional area values of glycopeptides determined using electrospray ionization-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS) correlated with retention times. These findings support the implementation of HILIC-mode HPLC to improve the characterization of glycosylated biopharmaceuticals.
      PubDate: 2017-04-13T16:50:29.01561-05:0
      DOI: 10.1002/bmc.3988
  • Simultaneous determination of difenoconazole, trifloxystrobin and its
           metabolite trifloxystrobin acid residues in watermelon under field
           conditions by GC − MS/MS
    • Authors: Di Kang; Haizhen Zhang, Yuling Chen, Fei Wang, Lihong Shi, Deyu Hu, Kankan Zhang
      Abstract: An optimized QuEChERS method for the simultaneous determination of difenoconazole, trifloxystrobin and its metabolite trifloxystrobin acid residues in watermelon and soil was developed and validated by gas chromatography with tandem mass spectrometry. The samples were extracted with acetonitrile (1% formic acid) and cleaned up by dispersive solid-phase extraction with octadecylsilane sorbent. The limit of quantification of the method was 0.01 mg/kg, and the limit of detection was 0.003 mg/kg for all three analytes. The recoveries of the fungicides in watermelon, pulp and soil were 72.32 − 99.20% for difenoconazole, 74.68 − 87.72% for trifloxystrobin and 78.59 − 92.66% for trifloxystrobin acid with relative standard deviations of 1.34 − 14.04%. The dissipation dynamics of difenoconazole and trifloxystrobin in watermelon and soil followed the first-order kinetics with half-lives of 3.2 − 8.8 days in both locations. The final residue levels of difenoconazole and trifloxystrobin were below 0.1 mg/kg (maximum residue level (MRL) set by China) and 0.2 mg/kg (MRL set by European Union), respectively, in pulp samples collected 14 days after the last application. These results could help Chinese authorities to establish MRL of trifloxystrobin in watermelon and provide guidance for the safe and proper application of both fungicides on watermelon.
      PubDate: 2017-04-12T05:18:22.227777-05:
      DOI: 10.1002/bmc.3987
  • Analytical challenges in quantifying abiraterone with LC-MS/MS in human
    • Authors: Guillemette E. Benoist; Eric Meulen, Floor J. E. Lubberman, Winald R. Gerritsen, Tineke J. Smilde, Jack A. Schalken, Jan H. Beumer, David M. Burger, Nielka P. Erp
      Abstract: A method was developed and validated to quantify abiraterone in human plasma. During assay development several analytical challenges were encountered: limited stability in patient samples, adsorption to glass, co-elution with metabolites, and carry-over issues. Limited stability (2 h) was found for abiraterone in fresh plasma as well as whole blood at ambient temperature. When kept at 2-8 °C, abiraterone in plasma was stable for 24 h and in whole blood for 8 h.Adsorption of abiraterone to glass materials was addressed by using polypropylene throughout the method. Carry-over was reduced to acceptable limits by incorporating a third mobile phase into the gradient. The chromatographic separation of abiraterone with its multiple metabolites was addressed by using a longer analytical column and adjusting the gradient. Abiraterone was extracted by protein precipitation, separated on a C18-column with gradient elution and analyzed with tandem quadrupole mass spectrometry in positive ion mode. A stable deuterated isotope was used as the internal standard. The assay ranges from 1-500 ng/mL. Within–and between day precisions and accuracies were below 13.4% and within 95-102%. This bioanalytical-method was successfully validated and applied to determine plasma concentrations of abiraterone in clinical studies and in regular patient care for patients with metastatic castration resistant prostate cancer.
      PubDate: 2017-04-03T03:30:21.080145-05:
      DOI: 10.1002/bmc.3986
  • RP HPLC enantioseparation of β-adrenolytics using micellar mobile
           phasewithout organic solvents
    • Authors: Shiv Alwera; Ravi Bhushan
      Abstract: Enantioseparation of a few commonly administered racemic β-adrenolytics (namely, carvedilol, betaxolol, salbutamol, and bisoprolol) has been achieved using a water micellar mobile phase containing surfactants (SDS and Brij-35) without organic solvents as a new approach in RPHPLC. Two CDRs based on enantiomerically pure (S)-(−)-levofloxacin were synthesized using N-hydroxysuccinimide and N-hydroxybenzotriazole as the activation auxiliaries. Diastereomeric derivatives of the chosen β-adrenolytics were synthesized under microwave irradiation in a very short reaction time. The (S)-(−)-levofloxacin moiety enhanced molar absorbance of the diastereomeric derivatives resulting into very low LOD (1.618 ng mL−1 and 4.902 ng mL−1, respectively, for diastereomeric derivatives of (RS)-Bxl and better resolution with lower retention times (for all the analytes), in comparison to literature reports. There was 15-20 times less consumption of mobile phase because of lower retention time.
      PubDate: 2017-03-31T04:10:44.495172-05:
      DOI: 10.1002/bmc.3983
  • Contents Variation Analysis of Free Amino Acids, Nucleosides and
           Nucleobases in Semen sojae praeparatum Fermentation Using UFLC-QTRAP MS
    • Authors: Chuan Chai; Xiaobing Cui, Chenxiao Shan, Sheng Yu, Hongmei Wen
      Abstract: UFLC–QTRAP MS was used to develop a sensitive and rapid method of evaluating content variation during Semen sojae praeparatum (SSP) fermentation. It did this through the simultaneous quantification of 22 free amino acids (FAAs) and 16 nucleosides and nucleobases (Ns) in the raw materials and processed products of SSP. The method was shown to be reproducible and accurate. The limits of detection (LOD) and quantity (LOQ) values were between 0.09-168.75 and 0.31-562.50 ng/mL for the 38 analytes, respectively. The data was examined through Principal Component Analysis (PCA) to compare the content variations. The quantitative results showed that the ingredients were properly determined in most of the samples and were converted regularly throughout the SSP fermentation process. These results correspond to the morphologic changes and PCA results.
      PubDate: 2017-03-31T04:10:31.342971-05:
      DOI: 10.1002/bmc.3985
  • Sensitive and Specific LC-ESI-MS/MS Method for Determination of ZYDPLA1, a
           Novel long acting DPP4 Inhibitor in Rat Plasma: An application for
           Toxicokinetics Study in Rats
    • Authors: Poonam Giri; Nirmal Patel, Bharat Patel, Harilal Patel, Rajesh Bahekar, Nuggehally R. Srinivas, Pankaj R. Patel, Ranjit Desai
      Abstract: A rapid and highly specific assay was developed and validated for estimation ofZYDPLA1 in rat plasma using liquid chromatography coupled to tandem mass spectrometry with positive electrospray ionization. Method validation comprised of parameters such as: specificity, matrix effect, precision, accuracy, recovery, stability etc. The assay procedure involved a simple protein precipitation of ZYDPLA1 and alprazolam (internal standard, IS) from rat plasma using acetonitrile. Chromatographic separation was achieved with a gradient mobile phase comprising of (A) 0.2% ammonia in purified water, (B) 0.1% formic acid in IPA: methanol (1:1 v/v) and (C) acetonitrile at a flow rate of 1 mL/min on an ACE-5, C18 (4.6 x 50 mm) column with run time of 5.5 min. The quantitation of ZYDPLA1 was achieved by summation of four MRM transitions (m/z 399.7  383.0, 399.7  276.10, 399.7  153.20, and 399.7  127.20), while that of IS was by a single MRM transition (m/z 309.10  281.00). The lower limit of quantitation achieved was 0.01μg/mL and the method showed linearity from 0.01 to 25 µg/mL. The intra- and inter-day precision (% CV) of the quality control sampleswas within8.81%and accuracy was ±10% of nominal values.This novel method wasapplied for evaluation of Toxicokinetics of ZYDLA1 in rats.
      PubDate: 2017-03-31T04:10:24.705228-05:
      DOI: 10.1002/bmc.3984
  • Determination of (4-(1,3-dioxo-1,3-dihydro-2H-isoindol-
           2-yl)-N′-[(4-ethoxyphenyl) methylidene] benzohydrazide, a novel
           anti-inflammatory agent, in biological fluids by UPLC-MS/MS: Assay
           development, validation and in vitro metabolic stability study
    • Authors: Muzaffar Iqbal; Mashooq A. Bhat, Mohammad Raish, Essam Ezzeldin
      Abstract: A thalidomide analogue, (4-(1,3-dioxo-1,3-dihydro-2H-isoindol- 2-yl)-N′-[(4-ethoxyphenyl) methylidene] benzohydrazide), has been identified as a promising broad spectrum anti-inflammatory agent in previous study. In this study, a sensitive and selective UPLC-MS/MS assay was developed and validated for its determination in rat plasma samples. The chromatographic separation was performed on Aquity BEH C18 column using mobile phase comprising of acetonitrile and 10 mM ammonium acetate in the ratio of 85:15, at flow rate of 0.3 mL min-1. The detection and quantification were performed in positive multiple reaction monitoring mode by parent to daughter ion transition of 414.06 ˃ 148.05 for analyte and 411.18 ˃ 191.07 for internal standard (risperidone), respectively using electrospray ionization source. The sample extraction process consisted of liquid liquid extraction method using diethyl ether as extracting solvent. The assay was validated by following FDA guideline and all parameters were found to be within the acceptable limits. The linearity was between 10.1 - 2500 ng mL-1 and LLOQ was 10.1 ng mL-1. The reported results indicate that the assay could meet the requirement for analysis of this compound in trace amounts expected to the present in actual samples. Further, in vitro metabolic stability study was performed in rat liver microsomes by using the validated assay.
      PubDate: 2017-03-31T03:49:02.28342-05:0
      DOI: 10.1002/bmc.3981
  • LC/Q-TOF profile and preliminary stability studies of an enriched
           flavonoid fraction of Cecropia pachystachya Trécul leaves with potential
           antidepressant-like activity
    • Authors: Caroline F. Ortmann; Helena M. Abelaira, Gislaine Z. Réus, Zuleide M. Ignácio, Vitor Clasen Chaves, Talitha Caldas dos. Santos, Pâmela Carvalho, Anelise S. Carlessi, Livia Bruchchen, Lucineia G. Danielski, Simone Gonçalves Cardoso, Angela M. Campos, Fabricia Petronilho, Joyce Rebelo, Meline O. S. Morais, Francieli Vuolo, Felipe Dal-Pizzol, Emilio L. Streck, João Quevedo, Flávio H. Reginatto
      Abstract: There is an increasing interest in natural antioxidants that are candidates for prevention of brain damage occurring in major depressive disorders. Cecropia pachystachya is a tropical tree species of Central and South America and is a rich source of polyphenols, especially flavonoids. The aim of this study was to characterize the flavonoid profile of an enriched flavonoid fraction of C. pachystachya (EFF-Cp) and evaluate the antidepressant-like effects of its acute administration in behavior, cytokine levels, oxidative stress and energy metabolism parameters. The EFF-Cp chemical characterization was performed by HPLC/DAD and LC/QTOF. The antidepressant-like effects were performed by forced swimming test (FST), splash test and open field test. EFF-Cp showed 15 flavonoids, including 7 new glycosyl flavonoids for C. pachystachya. Quantitatively EFF-Cp showed isoorientin (43.46 mg/g), orientin (23.42 mg/g) and isovitexin (17.45 mg/g) as major C-glycosylflavonoids. Also, EFF-Cp at the dose of 50 mg/kg and 100 mg/kg reduced the immobility time in FST, without changing the locomotor activity and grooming time. In addition, EFF- Cp was able to prevent the oxidative damage in some brain areas. In conclusion, the results of this study suggest that enriched C-glycosyl flavonoid fraction of Cecropia pachystachya (EFF- Cp) exerts antidepressant-like effects by its antioxidant properties.
      PubDate: 2017-03-31T02:40:57.57073-05:0
      DOI: 10.1002/bmc.3982
  • Use of LC-QqQ-MS for the detection of emodin metabolites in rat bile and
    • Authors: Songyan Wu; Yaqing Zhang, Zunjian Zhang, Rui Song
      Abstract: Emodin is the representative form of rhubarb, which is widely used in traditional Chinese medicine for the treatment of purgative, anti-inflammatory, antioxidative and antiviral, etc. Previous reports demonstrated that emodin glucuronide was the major metabolite in plasma. Due to the extensive conjugation reactions of polyphenols, the aim of this study was to identify the metabolites of emodin in rat bile and urine. Neutral loss and precursor ion scan methods of triple-quadrupole mass spectrometer revealed 13 conjugated metabolites in rat bile and 22 metabolites in rat urine, which including 4 phase I and 18 phase II metabolites. The major metabolites in rat bio-samples were emodin glucuronoconjugates. Moreover, rhein monoglucuronide, chrysophanol monoglucuronide and rhein sulfate were proposed for the first time after oral administration of emodin. Overall, liquid chromatography hybrid triple-quadrupole mass spectrometry (LC-QqQ-MS) analysis leads to the discovery of several novel emodin metabolites in rat bile and urine and underscores that conjugated with glucuronic acid is the main metabolic pathway.
      PubDate: 2017-03-25T08:30:38.348972-05:
      DOI: 10.1002/bmc.3979
  • Screening and identification of multiple constituents and their
           metabolites of Zhi-zi-chi decoction in rat urine and bile by
    • Authors: Wei Feng; Qiuju Dong, Minyan Liu, Si Li, Ting Liu, Xinguo Wang, Liying Niu
      Abstract: Zhi-zi-chi decoction (ZZCD) is a classical formula widely used in Chinese clinical application. In the present study, a novel and efficient strategy has been developed for screening and identification of multiple constituents and their metabolites of ZZCD using ultra high performance liquid chromatography combined with triple TOF mass spectrometry. The novel approach of an on-line data acquisition method dependent on multiple mass defect filter and dynamic background subtraction is combined with multiple data processing techniques. Firstly, a total of 109 potential bioactive compounds were detected in ZZCD. Based on the same instrumental conditions, 100 compounds were found in rat biofluids after oral administration of ZZCD, including 61 original compounds of ZZCD as well as 39 metabolites. Conjugations with sulfate, glucuronate, and amino acids were found as the predominant metabolic reaction of ZZCD. As more xenobiotics were detected in urine than those in bile, it demonstrated that multiple components of ZZCD have undergone comprehensive renal excretion. This study reported the urinary and biliary excretion in rats after oral administration of ZZCD for the first time. The present study expands our knowledge about the constituents and metabolism of ZZCD, which could be very useful for further pharmacological and clinical studies of ZZCD.
      PubDate: 2017-03-23T00:50:26.271968-05:
      DOI: 10.1002/bmc.3978
  • Free mycophenolic acid determination in human plasma ultrafiltrate by a
           validated liquid chromatography-tandem mass spectrometry method.
    • Authors: Paulina Łuszczyńska; Tomasz Pawiński, Paweł K. Kunicki, Katarzyna Sikorska, Ryszard Marszałek
      Abstract: ObjectivesThe aim of this study was to develop and fully validate LC-MS/MS method for free mycophenolic acid (MPA) concentration measurements in plasma ultrafiltrate that will be reliable and simple in preparation with deuterated MPA (MPA-d3) chosen as an internal standard.MethodsThe chromatographic separation was made with Zorbax Eclipse XDB-C18 column (4.6x150 mm) using a gradient of two solutions as a mobile phase: A) water and B) methanol, each containing 0.1% formic acid and 2.5 mM ammonium acetate.ResultsSatisfactory repeatability of retention times was achieved with average values of 7.54 ± 0.20 min and 7.50 ± 0.19 min for MPA and MPA-d3, respectively. The method was selective, with no carry-over or matrix effect observed. The analytical range was proven for MPA ultrafiltrate concentrations of 1-500 ng/mL. The accuracy and precision fell within the acceptance criteria for intraday (accuracy: 100.63-110.46%, imprecision: 6.23-7.76%), as well as interday assay (accuracy: 98.81-110.63%, imprecision: 5.36-10.22%). The method was used for free MPA determination in plasma samples from patients treated with mycophenolate mofetil.ConclusionsTo our best knowledge this is the first LC-MS/MS method for free MPA monitoring using MPA-d3 that allows to measure plasma ultrafiltrate concentrations as low as 1 ng/mL.
      PubDate: 2017-03-20T01:45:32.70541-05:0
      DOI: 10.1002/bmc.3976
  • UHPLC-MS/MS method for the determination of omarigliptin in rat plasma and
           its application to a pharmacokinetic study in rats
    • Authors: Meng-fang Li; Xiao-xia Hu, Ai-qun Ma
      Abstract: Omarigliptin is a novel long-acting DPP-4 inhibitor used for the treatment of T2DM. In this work, a sensitive and selective UHPLC-MS/MS method was developed and validated for determination of omarigliptin in rat plasma. Sample preparation was performed by protein precipitation with acetonitrile. Chromatographic separation of analytes was achieved on a RRHD Eclipse Plus C18 column (2.1 × 50 mm, 1.8 µ), using gradient mobile phase (0.1% formic acid-acetonitrile) at a flow rate of 0.4 mL/min. Detection was performed in multiple reaction monitoring mode, with target fragment ions m/z 399.1  152.9 for omarigliptin and m/z 237.1  194 for IS. The total run time was 4 min. Retention time of omarigliptin and IS was 1.25 and 2.12 min, respectively. RSD% of the intra- and inter-day precision was below 10.0%, and accuracy was between 97.9% and 105.3%. Calibration curve was established over the range of 2-5000 ng/mL with good linearity. The LLOQ and LOD of omarigliptin were 2 ng/mL and 0.25 ng/mL, respectively. Mean recoveries were in the range of 87.3-95.1% for omarigliptin. No matrix effect was observed in this method. This novel method has been successfully applied to a pharmacokinetic study of omarigliptin in rats. The absolute bioavailability of omarigliptin was identified as high as 87.31%.
      PubDate: 2017-03-19T21:30:33.498865-05:
      DOI: 10.1002/bmc.3975
  • Elucidation of stress-induced degradation products of mangiferin: Method
           development and validation
    • Authors: Rajneet Kaur Khurana; Satvinder Kaur, Jasleen Kaur, Bhupinder Singh
      Abstract: The degradation behavior of mangiferin, under various ICH Q1A(R2) recommended stress conditions, was studied using an isocratic elution with mobile phase (pH 2.4), composed of acetonitrile and 1% orthophosphoric acid (12:88 v/v) at a flow rate of 1.0 mL/min, with λmax 262 nm. It was suitably adapted for LC–MS studies by replacing with 1% acetic acid (ACN–1% acetic acid; 18:82) and the pH was adjusted to 3.0. Extensive degradation was found to occur during alkaline medium stress studies at 2.31 min of retention time at λmax of 235 nm. The mass spectrum of mangiferin, 3 h after treatment with 0.1 M NaOH, clearly shows the rupture of the tricyclic ring, indicating that a fragment at m/z − 269 was formed. Furthermore, the results were supported by nuclear magnetic resonance as well. However, no degradation was observed in other stress conditions.
      PubDate: 2017-03-13T21:30:37.810499-05:
      DOI: 10.1002/bmc.3935
  • Stability of doripenem in reconstituted solution – thermal and oxidative
           decomposition kinetics and degradation products by LC–MS
    • Authors: Fábio Souza Barbosa; José Pedro Etchepare Cassol, Luiz Alcides das Chagas Batista, Everson Willian Fialho Cordeiro, Marí Castro Santos, Adriana Raffin Pohlmann, Elfrides E. S. Schapoval, Cássia Virginia Garcia, Andreas Sebastian Loureiro Mendez
      Abstract: A ultra-fast liquid chromatography method applied to quantitation of doripenem in powder for injection was validated. Validation parameters were assayed and a rapid analysis was established by a reversed-phase system comprising a C18 column endcapped (50 × 4.0 mm, 2.0 μm), mobile phase consisting of phosphoric acid 0.01% (pH 3.8) and acetonitrile (98:02, v/v) and a flow rate of 0.4 mL min−1. Drug stability was studied through submission to forced conditions, allowing the major degradation products to be detected and the kinetics parameters to be established. Thermal and oxidative degradation were determined, and indicated a kinetic decomposition following first and second order, respectively. The main degradation products were identified by LC–MS analysis, and the results were evaluated in order to suggest the chemical structures corresponding to respective masses and fragmentations. Six compounds were identified, with m/z 411, 427, 437, 634, 650 and 664. All of them resulted from cleavage of β-lactam ring and alcoholic chain and/or dimerization. These experimental results provide valuable information about the stability of doripenem reconstituted solution and procedures for its handling and storage.
      PubDate: 2017-03-10T10:29:52.09915-05:0
      DOI: 10.1002/bmc.3940
  • A sensitive quantitative assay for the determination of propafenone and
           two metabolites, 5-hydroxypropafenone and N-depropylpropafenone, in human
           K2EDTA plasma using LC-MS/MS with ESI operated in a positive mode
    • Authors: Harilal Patel; Ashok Ghoghari, Chandrakant Bhatt, Shaival Shah, Anilkumar Jha, Nirmal Desai, Nuggehally R. Srinivas
      Abstract: Propafenone is a potent antiarrhythmic agent; clinically propafenone has been used for a number of cardiac arrhythmias because it possesses multiple modes of action, via beta adrenergic receptor blockade and calcium antagonistic activity. Propafenone (PPF) exhibits extensive saturable presystemic biotransformation (first pass effect) resulting into two active metabolites; 5- hydroxypropafenone (5-OH PPF) formed by CYP2D6 and N-depropylpropafenone (NDP) formed by both CYP3A4 and CYP1A2 enzymes. A specific and sensitive LC-MS/MS method was developed and validated for quantitation of PPF, 5-OH PPF and NDP using turboion spray in a positive ion mode. A solid phase extraction was employed for the extraction from human plasma. Chromatographic separation of analytes was achieved using an ACE-5 C8, (50 x 4.6 mm) column with a gradient mobile phase comprising of ammonium acetate containing 0.01% TFA in purified water and acetonitrile. The retention time was achieved 1.36, 1.23, 1.24 min and 1.34 min for PPF, 5-OH PPF, NDP and IS (carbamazepine), respectively. Quantitation was performed by monitoring MRM transition pairs of m/z 342.30 to m/z 116.20, m/z 358.30 to m/z 116.20, m/z 300.30 to m/z 74.20 and m/z 237.20 to m/z 194.10, respectively. The developed method was validated for various parameters. The calibration curves of PPF and 5-OH PPF showed linearity from 1-500 ng/mL, with a lower limit of quantitation of 1.0 ng/mL and for NDP linearity from 0.1-25 ng/mL with a lower limit of quantitation of 0.1 ng/mL. The bias and precision for intra-and-inter batch assays were less than 10% and 5%, respectively. The developed assay was used to evaluate pharmacokinetic properties of propafenone and its major metabolites in healthy human subjects.
      PubDate: 2017-03-06T03:10:28.069573-05:
      DOI: 10.1002/bmc.3967
  • Development and validation of a reversed-phase high-performance liquid
           chromatographic method with solid-phase extraction for the quantification
           of hydrochlorothiazide in ex vivo permeation studies
    • Authors: R. Onnainty; E.M. Schenfeld, M.R. Longhi, M.A. Quevedo, G.E. Granero
      Abstract: Hydrochlorothiazide (HCT) is a diuretic used to treat hypertension. In order to study its intestinal permeation behavior applying an ex vivo methodology, a rapid, sensitive and selective reversed-phase liquid chromatography (RP-HPLC) method coupled with UV detection (RP-HPLC UV) was developed for the analysis of HCT in TC199 culture medium used as mucosal and serosal solutions in the everted rat intestinal sac model. Also, analytical procedures for the quantification of HCT by RP-HPLC with UV detection required a sample preparation step by solid-phase extraction. The method was validated in the concentration range of 8.05 × 10−7 to 3.22 × 10−5 m for HCT. Chromatographic parameters, namely carry-over, lower limit of quantification (1.4491 × 10−7 m), limit of detection (3.8325 × 10−8 m), selectivity, inter- and intraday precision and extraction recovery, were determined and found to be adequate for the intended purposes. The validated method was successfully used for permeability assays across rat intestinal epithelium applying the ex vivo everted rat gut sac methodology to study the permeation behavior of HCT.
      PubDate: 2017-03-02T22:40:46.794208-05:
      DOI: 10.1002/bmc.3943
  • Abnormal levels of seven amino neurotransmitters in depressed rat brain
           and determination by HPLC-FLD
    • Authors: Ting Cui; Hong-Mei Qiu, Dan Huang, Qi-Xin Zhou, Xiao-Yan Fu, Hai-Yan Li, Xin-Hui Jiang
      Abstract: The determination of amino acids with actions like neurotransmitters or modulators has been increasingly important for diagnosis in many neuropsychiatric diseases. A rapid and simple high-performance liquid chromatography with fluorescence detection method was developed for simultaneous determination of seven amino acids: aspartate (Asp), glutamate (Glu), serine (Ser), glutamine (Gln), glycine (Gly), taurine (Tau) and γ-aminobutyric` acid (GABA). Homoserine was used as an internal standard. The analysis was performed on a BDS column with methanol and 50 mm sodium acetate solution (pH 6.5) using a simple gradient elution. Several parameters of the developed method were validated including linearity, accuracy, precision, extraction recovery and stability, which were within the acceptable range. The method was successfully applied to determination of real samples: hippocampus and cortex in depressed rats exposed to chronically unpredictable stress in order to study if there existed differences in the seven amino acids levels between depressed rats and control. The results showed that Asp, Gly, Tau and GABA significantly decreased with increasing Gln in the hippocampus of depressed rats, compared with that of the control group, among which obviously lower level of Asp and higher level of Gln in cortex were observed. The analytical method and the results could be useful for clinical diagnosis and further insight into pathophysiological mechanism of depression.
      PubDate: 2017-03-02T22:35:31.455222-05:
      DOI: 10.1002/bmc.3937
  • Simultaneous determination of mycophenolic acid and its glucuronide and
           glycoside derivatives in canine and feline plasma by UHPLC-UV
    • Authors: Sol Maiam Rivera; Julianne K. Hwang, Jeniffer E. Slovak, Michael H. Court, Nicolas F. Villarino
      Abstract: Cats and dogs can suffer from multiple autoimmune diseases. Mycophenolic acid (MPA) is a potentially useful immunosuppressant drug in cats and dogs, because of its well-documented efficacy in controlling autoimmune disease in humans. However, the pharmacokinetics and pharmacodynamics in these species remain to be determined. We have developed and validated a sensitive, precise, accurate and reproducible method that provides consistent quantification of MPA and its major derivatives, MPA phenol glucoside and MPA phenol glucuronide, in canine and feline plasma using ultra-high-pressure liquid chromatography coupled to an ultraviolet detector. The main advantages of this novel method include a small sample volume, easy sample preparation, a short chromatographic analysis time and the option to select either phenolphthalein β-d-glucuronide or mycophenolic acid carboxybutoxy ether as internal standard. Results of validation indicate that this analytical method is suitable to study the plasma disposition of MPA and its derivatives in dogs and cats.
      PubDate: 2017-02-27T23:30:47.342272-05:
      DOI: 10.1002/bmc.3942
  • A UPLC–MS/MS method for analysis of vancomycin in human cerebrospinal
           fluid and comparison with the chemiluminescence immunoassay
    • Authors: Shenghui Mei; Jiaqing Wang, Leting Zhu, Ruiling Chen, Xingang Li, Kai Chen, Guangqiang Chen, Jianxin Zhou, Qiang Wang, Zhigang Zhao
      Abstract: Vancomycin (VCM) is clinically used in treating patients with postoperative intracranial infections. The cerebrospinal fluid (CSF) concentration of VCM varies greatly among patients. To guide the dosage regimens, monitoring of VCM in CSF is needed. However a method for analysis of VCM in human CSF is lacking. An ultraperformance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) was developed and validated for analysis of VCM in human CSF, and the agreement of UPLC–MS/MS and chemiluminescence immunoassay (CLIA) in the analysis of CSF VCM was evaluated. The ion transitions were m/z 725.5 > 144.1 for VCM and m/z 455.2 > 308.2 for methotrexate (internal standard). The agreement between UPLC–MS/MS and CLIA was evaluated by Bland–Altman plot in 179 samples. The calibration range of the UPLC–MS/MS method was 1–400 mg/L. The inaccuracy and imprecision were −0.69–10.80% and  0.98). The 95% limit of agreement of the ratio of CLIA to UPLC-MS/MS was 61.66–107.40%. Further studies are warranted to confirm the results.
      PubDate: 2017-02-20T20:05:51.673121-05:
      DOI: 10.1002/bmc.3939
  • Liquid chromatography high resolution mass spectrometry for the
           determination of baclofen and its metabolites in plasma: Application to
           therapeutic drug monitoring
    • Authors: Laurence Labat; Antonio Goncalves, Ana Rita Marques, Bénédicte Duretz, Bernard Granger, Xavier Declèves
      Abstract: Baclofen is used to manage alcohol dependence. This study describes a simple method using liquid chromatography coupled to high-resolution mass spectrometry (LC-HR-MS) developed in plasma samples. This method was optimized to allow quantification of baclofen and determination of metabolic ratio of its metabolites, an oxidative deaminated metabolite of baclofen (M1) and its glucuronide form (M2). The LC-HR-MS method on Exactive® apparatus is a newly developed method with all the advantages of high resolution in full-scan mode for the quantification of baclofen and detection of its metabolites in plasma. The present assay provides a protein precipitation method starting with 100 μL plasma giving a wide polynomial dynamic range (R2 > 0.999) between 10 and 2000 ng/mL and a lower limit of quantitation of 3 ng/mL for baclofen. Intra- and inter-day precisions were
      PubDate: 2017-02-17T03:00:28.825853-05:
      DOI: 10.1002/bmc.3936
  • Preclinical pharmacokinetics of novel trioxane antimalarial drug (99/411)
           – several unanswered questions and development perspectives
    • Authors: Nuggehally R. Srinivas
      PubDate: 2017-02-16T21:05:24.130974-05:
      DOI: 10.1002/bmc.3938
  • Comparative pharmacokinetic study of the main components of cortex fraxini
           after oral administration in normal and hyperuricemic rats
    • Authors: Yinan Wang; Min Zhao, Hao Ye, Yizhen Shao, Yongbo Yu, Miao Wang, Chunjie Zhao
      Abstract: Cortex Fraxini is an important traditional Chinese herbal medicine used for the treatment of gout and hyperuricemia. An efficient and rapid ultra-performance liquid chromatography mass spectrometry method was developed and validated for simultaneous quantitation of six coumarins (aesculin, fraxin, aesculetin, fraxetin, sopoletin and 7-hydroxycoumarin) in normal and hyperuricemic rats plasma after oral administration of Cortex Fraxini. The method could successfully be applied for pharmacokinetics studies. The pharmacokinetic behavior of six coumarins in normal and hyperuricemia rats plasma was determined. Results showed that, for some of analytes, the pharmacokinetic parameters (AUC0–t, AUC0–∞, Cmax, Tmax and CL) were significantly different between normal and hyperuricemic rats. The different pharmacokinetic parameters might result from renal impairment or a change of metabolic enzymes in the pathological state. The pharmacokinetic study in pathological state could provide more useful information to guide the clinical use of traditional Chinese herbal medicine.
      PubDate: 2017-02-16T20:30:36.38204-05:0
      DOI: 10.1002/bmc.3934
  • Comparative study on fatty acid composition of olive (Olea europaea L.),
           with emphasis on phytosterol contents
    • Authors: Ali Ozkan; Hassan Y. Aboul-Enein, Muhittin Kulak, Recep Bindak
      Abstract: The present study was designed to determine the fatty acid composition and phytosterol contents of Turkish native olive cultivars, namely Kilis Yağlık and Nizip Yağlık cv. In this context, olive fruits from 34 locations were sampled and then screened for their components in comparison. Fifteen different fatty acids were found in both olive oils. In the order of abundance, the most important ones were oleic acid (18:1) > palmitic acid (16:0) > linoleic acid (18:2) > stearic acid (18:0). Significant differences were observed in the contents of oleic acid (18:1), palmitic acid (16:0), linoleic acid (18:2) but not for stearic acid content in comparison both oils (p 
      PubDate: 2017-02-06T23:20:26.215404-05:
      DOI: 10.1002/bmc.3933
  • D-Optimal mixture design optimization of an HPLC method for simultaneous
           determination of commonly used antihistaminic parent molecules and their
           active metabolites in human serum and urine
    • Authors: Selvakumar Kanthiah; Valliappan Kannappan
      Abstract: This study describes a specific, precise, sensitive and accurate method for simultaneous determination of hydroxyzine, loratadine, terfenadine, rupatadine and their main active metabolites cetirizine, desloratadine and fexofenadine, in serum and urine using meclizine as an internal standard. Solid-phase extraction method for sample clean-up and preconcentration of analytes was carried out using Phenomenex Strata-X-C and Strata X polymeric cartridges. Chromatographic analysis was performed on a Phenomenex cyano (150 × 4.6 mm i.d., 5 μm) analytical column. A D-optimal mixture design methodology was used to evaluate the effect of changes in mobile phase compositions on dependent variables and optimization of the response of interest. The mixture design experiments were performed and results were analyzed. The region of ideal mobile phase composition consisting of acetonitrile–methanol–ammonium acetate buffer (40 mm; pH 3.8 adjusted with acetic acid): 18:36:46% v/v/v was identified by a graphical optimization technique using an overlay plot. While using this optimized condition all analytes were baseline resolved in
      PubDate: 2017-02-05T23:20:27.906364-05:
      DOI: 10.1002/bmc.3932
  • Untargeted metabolomic profiling of seminal plasma in nonobstructive
           azoospermia men: A noninvasive detection of spermatogenesis
    • Authors: Kambiz Gilany; Ahmad Mani-Varnosfaderani, Arash Minai-Tehrani, Fateme Mirzajani, Alireza Ghassempour, Mohammed Reza Sadeghi, Mehdi Amini, Hassan Rezadoost
      Abstract: Male factor infertility is involved in almost half of all infertile couples. Lack of the ejaculated sperm owing to testicular malfunction has been reported in 6–10% of infertile men, a condition named nonobstructive azoospermia (NOA). In this study, we investigated untargeted metabolomic profiling of the seminal plasma in NOA men using gas chromatography–mass spectrometry and advance chemometrics. In this regard, the seminal plasma fluids of 11 NOA men with TESE-negative, nine NOA men with TESE-positive and 10 fertile healthy men (as a control group) were collected. Quadratic discriminate analysis (QDA) technique was implemented on total ion chromatograms (TICs) for identification of discriminatory retention times. We developed multivariate classification models using the QDA technique. Our results revealed that the developed QDA models could predict the classes of samples using their TIC data. The receiver operating characteristic curves for these models were>0.88. After recognition of discriminatory retention time's asymmetric penalized least square, evolving factor analysis, correlation optimized warping and alternating least squares strategies were applied for preprocessing and deconvolution of the overlapped chromatographic peaks. We could identify 36 discriminatory metabolites. These metabolites may be considered discriminatory biomarkers for different groups in NOA.
      PubDate: 2017-02-05T21:40:30.114842-05:
      DOI: 10.1002/bmc.3931
  • Enantiomeric resolution, stereochemical assignment and toxicity evaluation
           of TPA enantiomers
    • Authors: Yulang Chi; Zhijun Wu, Yi Zhong, Sijun Dong
      Abstract: Tetrahydro-α-(1-methylethyl)-2-oxo-1(2H)-pyrimidineacetic acid (TPA) is a critical intermediate in the synthesis of HIV protease inhibitors. A simple and efficient method for the separation and determination of TPA enantiomers was developed. The TPA was separated into its enantiomers with an enantiomeric purity of 99% using an HPLC system equipped with a Chiralpak OD-H column. Semi-preparative HPLC enantioseparations were carried out for further enrichment of the enantiomers. The validity of this method was evaluated on the basis of its precision, accuracy, linearity and recovery. The method was observed to be suitable for the rapid separation and semi-preparation of TPA isomers. The separated enantiomers were identified by optical rotation and high-resolution electrospray ionization mass spectrometry. Furthermore, the stereochemical structures of the TPA enantiomers were definitively confirmed using a combination of experimental and calculated electronic circular dichroism spectra. The toxicity of the separated pure enantiomers against Oryzias melastigma was evaluated using the median lethal concentration (LC50) values. The results indicated that (S)-(−)-TPA is ~2.5 times more toxic than its enantiomorphism.
      PubDate: 2017-02-02T21:30:25.823563-05:
      DOI: 10.1002/bmc.3924
  • Characterization of isochlorogenic acid A metabolites in rats using
           high-performance liquid chromatography/quadrupole time-of-flight mass
    • Authors: Jing Wang; Guoxiu Cao, Hong Wang, Hui Ye, Yunxi Zhong, Guangji Wang, Haiping Hao
      Abstract: Isochlorogenic acid A is widely present in fruits, vegetables and herbal medicines, and is characterized by anti-inflammatory, hepatoprotective and antiviral properties. However, little is known about its metabolic fate and pharmacokinetic properties. This study is thus designed to investigate the metabolic fate of isochlorogenic acid A. An analytical method based on high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC/Q-TOF MS) was established to characterize the metabolites of isochlorogenic acid A in the plasma, urine and feces of rats. A total of 32 metabolites were identified. The metabolic pathways mainly include hydrolyzation, dehydroxylation, hydrogenation and conjugation with methyl, glucuronic acid, glycine, sulfate, glutathione and cysteine. Moreover, the pharmacokinetic profiles of all the circulating metabolites were investigated. M11 resulting from hydrolyzation, dehydroxylation and hydrogenation was the dominant circulating metabolite after the intragastric administration of isochlorogenic acid A. The results obtained will be useful for further study of elucidating potential bioactive metabolites which can provide better explanation of the pharmacological and/or toxicological effects of this compound.
      PubDate: 2017-02-01T21:05:49.451576-05:
      DOI: 10.1002/bmc.3927
  • Simultaneous determination of eight bioactive components of Qishen Yiqi
           Dripping Pills in rat plasma using UFLC-MS/MS and its application to a
           pharmacokinetic study
    • Authors: Yaping Shao; Wen Zhang, Ling Tong, Jingyi Huang, Dongxiang Li, Wei Nie, Yan Zhu, Yunfei Li, Tao Lu
      Abstract: In this study, a rapid and reliable ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method was developed and validated for the simultaneous determination of eight active ingredients, including astragaloside IV (AIV), ononin (ONO), tanshinol (TSL), protocatechualdehyde (PCA), protocatechuic acid (PA), salvianolic acid D (SAD), rosmarinic acid (RA), and ginsenoside Rg1 (GRg1), in rat plasma. The plasma samples were pretreated by protein precipitation with acetonitrile. Chromatographic separation was performed on a Waters Acquity UPLC® BEH C18 column (1.7 µm particles, 2.1 × 100 mm).The mobile phase consisted of 0.1% aqueous formic acid (A)-acetonitrile with 0.1% formic acid (B) at a flow rate of 0.4 mL/min. Quantification was performed on a triple quadruple tandem mass spectrometry with electrospray ionization by multiple reaction monitoring both in the negative and positive ion mode. The lower limit of quantification (LLOQ) of TSL was 2.0 ng/mL and the others were 5.0 ng/mL. The extraction recoveries, matrix effects, intra- and inter-day precision and accuracy of eight tested components were all within acceptable limits. The validated method was successfully applied to the pharmacokinetic study of the eight active constituents after intragastric administration of three doses (1.0, 3.0, 6.0 g/kg body weight) of Qishen Yiqi dripping pills to rats.
      PubDate: 2017-02-01T12:40:27.090364-05:
      DOI: 10.1002/bmc.3941
  • Solid-phase microextraction of methadone in urine samples by
           electrochemically co-deposited sol–gel/Cu nanocomposite fiber
    • Authors: Sirwan Mohammadiazar; Fateme Hasanli, Mehdi Maham, Somayeh Payami Samarin
      Abstract: Electrochemically co-deposited sol–gel/Cu nanocomposites have been introduced as a novel, simple and single-step technique for preparation of solid-phase microextraction (SPME) coating to extract methadone (MDN) (a synthetic opioid) in urine samples. The porous surface structure of the sol–gel/Cu nanocomposite coating was revealed by scanning electron microscopy. Direct immersion SPME followed by HPLC-UV determination was employed. The factors influencing the SPME procedure, such as the salt content, desorption solvent type, pH and equilibration time, were optimized. The best conditions were obtained with no salt content, acetonitrile as desorption solvent type, pH 9 and 10 min equilibration time. The calibration graphs for urine samples showed good linearity. The detection limit was about 0.2 ng mL−1. Also, the novel method for preparation of nanocomposite fiber was compared with previously reported techniques for MDN determination. The results show that the novel nanocomposite fiber has relatively high extraction efficiency.
      PubDate: 2017-01-30T21:10:50.607433-05:
      DOI: 10.1002/bmc.3926
  • Determination of a natural DNMT1 inhibitor, peperomin E, in rat plasma by
           UFLC-MS/MS and method application in a pharmacokinetic study
    • Authors: Xin-zhi Wang; Hong-mei Wen, Chuan Chai, Wen-ying Zhang, Ming Gao, Rui Liu, Hao Wu, Jing-yu Liang
      Abstract: Peperomin E (PepE), a naturally occurring secolignan isolated from Peperomia dindygulensis, has drawn much attention recently owing to its anticancer and DNA methyltransferase 1 (DNMT1) inhibitory activity. Here, a simple and sensitive ultra-fast liquid chromatography–tandem mass spectrometry method was developed and validated for the determination of PepE in rat plasma for the first time. Samples were prepared by simple protein precipitation. Separation was performed on an XBridge™ C18 column using a mobile phase of acetonitrile and 0.1% (v/v) aqueous formic acid. PepE and the internal standard arctigenin were detected in a positive-ion mode using multiple reaction monitoring of the transitions at m/z 413.2  261.0 and 373.2  137.2, respectively. The calibration curve for PepE was linear over the range of concentrations of 1.46–6000 ng/mL, with a lower limit of quantitation of 1.46 ng/mL. Both intra- and interday precisions were within 11.05%, and the accuracy ranged from −11.5 to 5.51%. The extraction recovery and matrix effect were within acceptable limits. Stability tests showed that PepE remained stable throughout the analytical procedure. The validated method was then used to analyze the pharmacokinetics of PepE administered to rats orally (12.5 and 25 mg/kg) or intravenously (6.25 and 12.5 mg/kg).
      PubDate: 2017-01-29T22:36:02.236057-05:
      DOI: 10.1002/bmc.3930
  • A simple and selective UHPLC–MS/MS method for quantification of
           plantagoguanidinic acid in rat plasma and its application to a
           pharmacokinetic study
    • Authors: Ruijian Zhong; Yan Yu, Yangbing Zheng, Weikang Chen, Guoping Zhou, Jianhong Ding, Mingming Yuan
      Abstract: A simple, sensitive and specific UHPLC–MS/MS method for quantification of plantagoguanidinic acid (PGA) in rat plasma was applied to investigate the pharmacokinetic behavior in vivo, using protopine as internal standard. The chromatography was separated on a Phenomenex® Luna-C18 column (2.1 × 150 mm, 3.0 μm) within 7.0 min using a mobile phase consisting of acetonitrile–0.1% formic acid solution under gradient elution at a flow rate of 0.4 mL/min. Prepared samples were monitored by multiple reaction monitoring mode, with the target fragmentions m/z 226.2  84.2 for PGA and m/z 354.2  188.9 for IS in positive electrospray ionization. The calibration curve of PGA was linear throughout the range 1–1000 ng/mL (r = 0.9962). The lower limit of quantitation in plasma for PGA was 0.1 ng/mL, and the recovery was>88.6%. Intra- and interday accuracy ranged from −8.6 to 4.9%. Furthermore, this validated method was successfully used for a pre-clinical pharmacokinetic study of PGA at a single dose of 20 and 5 mg/kg in rats via oral and intravenous administration. The study showed that PGA was absorpted rapidly and eliminated gradually with a greater absolute oral bioavailability of 70.1% in rats.
      PubDate: 2017-01-25T20:20:27.580017-05:
      DOI: 10.1002/bmc.3929
  • Development of a UPLC-MS/MS method for routine therapeutic drug monitoring
           of aripiprazole, amisulpride, olanzapine, paliperidone and ziprasidone
           with a discussion of their therapeutic reference ranges for Chinese
    • Authors: Shao-Ting Wang; Yan Li
      Abstract: A highly feasible and reliable ultra-high performance liquid chromatography tandem mass spectrometry method was presented for therapeutic drug monitoring of five anti-schizophrenic drugs (amisulpride, olanzapine, aripiprazole, paliperidone and ziprasidone) simultaneously. To meet the requirements of practical clinical usage (easy handling, high throughput and cost effectiveness), the pretreatment process was simplified (only including protein precipitation and mobile phase dilution steps) and the UPLC separation cycle was set within 6 min. The whole methodology was carefully validated according to the latest international guidelines showing the excellent selectivity, accuracy, precision, applicability and stability. After a 10 month clinical application, a retrospective analysis of 253 positive samples was carried out to investigate conformance with the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie therapeutic reference range for Chinese patients. The results suggested good consistency for olanzapine, aripiprazole, paliperidone and ziprasidone, while for amisulpride, the plasma concentration level (445.2 ± 231.5 ng/mL) was relatively higher than the recommended range (100–320 ng/mL). We supposed that such phenomenon indicated the necessity of reconstructing a Chinese-specific therapeutic reference range for amisulpride treatment, which would be helpful to improve medication efficiency and safety for Chinese patients.
      PubDate: 2017-01-25T20:16:12.542028-05:
      DOI: 10.1002/bmc.3928
  • Rapid determination of oxindole alkaloids in cat's claw by HPLC using
           ionic liquid-based microwave-assisted extraction and silica monolithic
    • Authors: Chih-Wei Chang; Yu-Ying Yeh, Li-Ching Chang, Mei-Chich Hsu, Yu-Tse Wu
      Abstract: Cat's claw is a large woody vine with hook-like thorns, and has been traditionally used to treat inflammatory disorders in South and Central America. In this study, a rapid, validated high-performance liquid chromatographic (HPLC) method using a silica monolithic column was developed for the simultaneous determination of oxindole alkaloids, namely rhynchophylline, pteropodine, isomitraphylline and isopteropodine, in cat's claw. The ionic liquid-based microwave-assisted extraction (ILMAE), considered as an environmentally friendly and powerful tool, was first applied in the extraction of oxindole alkaloids. To optimize the HPLC method, the stationary phases, pH values of mobile phase and flow rates were investigated. The validated HPLC method using a Monolithic RP18e column (100 × 4.6 mm) enables these analytes to be separated almost twice as fast as with a conventional particulate column (~16 vs ~30 min) with limits of quantification and detection of 0.5 and 0.15 μg/mL, respectively. The ILMAE conditions were optimized by the Taguchi orthogonal array design. In comparison with conventional water boiling extraction, ILMAE offers almost four times higher yields within an extremely short extraction time. The developed HPLC coupled with ILMAE method could be efficient and practical for rapid determination of oxindole alkaloids in cat's claw.
      PubDate: 2017-01-24T23:45:37.420524-05:
      DOI: 10.1002/bmc.3925
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