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  Subjects -> CHEMISTRY (Total: 841 journals)
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    - CHEMISTRY (593 journals)
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CHEMISTRY (593 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: 34)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 18)
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: 233)
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: 55)
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 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: 15)
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: 68)
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: 14)
American Mineralogist     Hybrid Journal   (Followers: 14)
Analyst     Full-text available via subscription   (Followers: 40)
Angewandte Chemie     Hybrid Journal   (Followers: 224)
Angewandte Chemie International Edition     Hybrid Journal   (Followers: 213)
Annales UMCS, Chemia     Open Access   (Followers: 1)
Annals of Clinical Chemistry and Laboratory Medicine     Open Access   (Followers: 3)
Annual Reports in Computational Chemistry     Full-text available via subscription   (Followers: 3)
Annual Reports Section A (Inorganic Chemistry)     Full-text available via subscription   (Followers: 4)
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: 15)
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: 4)
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: 295)
Biochemistry Insights     Open Access   (Followers: 6)
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: 119)
Bioorganic & Medicinal Chemistry Letters     Hybrid Journal   (Followers: 97)
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: 3)
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: 66)
Catalysis for Sustainable Energy     Open Access   (Followers: 7)
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: 8)
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: 13)
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: 175)
Chemical Science     Open Access   (Followers: 22)
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: 57)
Chemie-Ingenieur-Technik (Cit)     Hybrid Journal   (Followers: 26)
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: 142)
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: 44)
Chemistry of Materials     Full-text available via subscription   (Followers: 258)
Chemistry of Natural Compounds     Hybrid Journal   (Followers: 9)
Chemistry World     Full-text available via subscription   (Followers: 22)
Chemistry-Didactics-Ecology-Metrology     Open Access   (Followers: 1)
ChemistryOpen     Open Access   (Followers: 2)
Chemkon - Chemie Konkret, Forum Fuer Unterricht Und Didaktik     Hybrid Journal  
Chemoecology     Hybrid Journal   (Followers: 3)
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)
Clay Minerals     Full-text available via subscription   (Followers: 10)
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: 7)
Combinatorial Chemistry & High Throughput Screening     Hybrid Journal   (Followers: 4)
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   (Followers: 1)
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: 12)
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: 58)
Dalton Transactions     Full-text available via subscription   (Followers: 22)
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: 8)
Environmental Chemistry Letters     Hybrid Journal   (Followers: 4)
Environmental Science & Technology Letters     Full-text available via subscription   (Followers: 5)
Environmental Science : Nano     Partially Free   (Followers: 1)
Environmental Toxicology & Chemistry     Hybrid Journal   (Followers: 17)

        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  [1577 journals]
  • A Rapid and Simple HPTLC Assay for Therapeutic Drug Monitoring of
           Capecitabine in Colorectal Cancer Patients
    • Authors: Sonali G. Thorat; Rupesh V. Chikhale, Madhukar R. Tajne
      Abstract: Capecitabine is a prodrug of 5-flurouracil, employed as a broad spectrum chemotherapeutic agents. It is also used as monotherapy or a combination chemotherapy agent for treatment of colorectal cancer. Capecitabine is administered in combination with oxaliplatin and hence it becomes essential to determine that co-administration does not affect its metabolism. To determine the plasma concentration of capecitabine a simple HPTLC method was developed and validated. Blood samples from 12 patients with colorectal cancer were collected and analysed by the HPTLC method with a reference internal standard. Out of these 12 patients, 6 were treated with capecitabine monotherapy and another 6 were treated with capecitabine + oxaliplatin combination therapy. The results of analysis indicated that there is no significant drug-drug interaction and the co-administration of oxaliplatin did not affect the metabolism of capecitabine. This method is sensitive, robust and specific and allows analysis of multiple samples simultaneously making it suitable for therapeutic drug monitoring of capecitabine.
      PubDate: 2017-09-22T22:25:20.910084-05:
      DOI: 10.1002/bmc.4100
       
  • Simultaneous determination of serum propafenone and its metabolites using
           high-performance liquid chromatography
    • Authors: Yuki Shirayama; Kosuke Doki, Yukio Sekiguchi, Kazutaka Aonuma, Yukinao Kohda, Masato Homma
      Abstract: Propafenone, a class Ic antiarrhythmic agent, is metabolized to 5-hydroxypropafeone (5-OHP) and N-depropylpropafenone (NDPP). Simultaneous determination of serum propafenone and its metabolites was performed using high-performance liquid chromatography (HPLC) equipped with a conventional octadecylsilyl silica column and ultraviolet detector. The wavelength was set at 250 nm. Propafenone and its metabolites in the serum were extracted using diethyl ether. The mobile phase solution, comprising 1-pentanesulfonic acid sodium salt (0.1 M), acetonitrile, and acetic acid (280:185:2.5, v/v/v), was pumped at a flow rate of 1 ml/min. The recoveries of propafenone, 5-OHP, and NDPP were greater than 85, 82, and 60%, respectively, with the coefficients of variation (CVs) less than 5.4, 1.9, and 2.9%, respectively. The calibration curves were linear for a concentration range of 12.5–1500 ng/ml for propafenone and 2–500 ng/ml for 5-OHP and NDPP (r> 0.999). CVs in the intra-day assays were 1.0%–3.8% for propafenone, 0.6%–2.0% for 5-OHP, and 0.6%–1.7% for NDPP. CVs in inter-day assays were 1.3%–7.7% for propafenone, 1.1%–6.5% for 5-OHP, and 5.4%–8.0% for NDPP. The present HPLC method can be used to assess the disposition of propafenone and its metabolites for pharmacokinetic studies and therapeutic drug monitoring of propafenone.
      PubDate: 2017-09-19T19:40:30.883166-05:
      DOI: 10.1002/bmc.4099
       
  • Simple determination of betaine, L-carnitine and choline in human urine
           using self-packed column and column-switching ion chromatography with
           non-suppressed conductivity detection
    • Authors: Dan Wei; Yan Zhu, Ming Guo
      Abstract: A sequential on-line extraction, clean-up and separation system for the determination of betaine, L-carnitine and choline in human urine using column-switching ion chromatography with non-suppressed conductivity detection was developed in this work. Self-packed pretreatment column (50 mm×4.6 mm, i.d.) was used for the extraction and clean-up of betaine, L-carnitine and choline. The separation was achieved using self-packed cationic exchange column (150 mm×4.6 mm, i.d.), followed by non-suppressed conductivity detection. Under optimized experimental conditions, the developed method presented good analytical performance, with excellent linearity in ranged of 0.60-100 μg mL-1 for betaine, 0.75-100 μg mL-1 for L-carnitine and 0.50-100 μg mL-1 for choline, with all correlation coefficient (R2) above 0.99 in urine. The limits of detection (LOD) were of 0.15 μg mL-1 for betaine and 0.20 μg mL-1 for L-carnitine and 0.09 μg mL-1 for choline. The intra- and inter-day accuracy and precision for all quality controls were within ±10.32% and ±9.05%, respectively. Satisfactory recovery was observed between 92.8% and 102.0%. The validated method was successfully applied to the detection of urinary samples from 10 healthy people. The values detected in human urine using the proposed method had a good agreement with the measurement reported previously.
      PubDate: 2017-09-15T20:00:50.715356-05:
      DOI: 10.1002/bmc.4098
       
  • Dynamic residual pattern of azoxystrobin in Swiss chard with contribution
           to safety evaluation
    • Authors: Waziha Farha; A.M. Abd El-Aty, Md. Musfiqur Rahman, Md. Humayun Kabir, Hyung Suk Chung, Han Sol Lee, Jong-Sup Jeon, Jing Wang, Byung-Joon Chang, Ho-Chul Shin, Jae-Han Shim
      Abstract: This study aimed at quantifying the residual amount of azoxystrobin in Swiss chard samples grown under greenhouse conditions at 2 different locations (Gwangju and Naju, Republic of Korea). Samples were extracted with acetonitrile, separated by salting out, and subjected to purification by using solid-phase extraction (SPE). The analyte was identified using liquid chromatography (LC)-ultraviolet detector (UVD). The linearity of the calibration range was excellent with coefficient of determination (R2) =1.00. Recovery at 3 different spiking levels (0.1, 0.5, and 4 mg/kg) ranged between 82.89 and 109.46% with relative standard deviation (RSD) < 3. The limit of quantification (LOQ), 0.01 mg/kg was considerably much lower than the maximum residue limit (MRL = 50 mg/kg) set by the Korean Ministry of Food and Drug Safety. The developed methodology has been successfully used for field treated leaves, which were collected randomly at 0 to 14 days following azoxystrobin application. The rate of disappearance in/on Swiss chard was ascribed to 1st order kinetics with a half-life of 8 and 5 days, in leaves grown at Gwangju and Naju greenhouses, respectively. Risk assessments revealed that the acceptable daily intake percentage (ADI%) is substantially below the risk level of consumption, at day 0 (in both areas), thus encouraging its safe consumption.
      PubDate: 2017-09-15T19:15:59.880259-05:
      DOI: 10.1002/bmc.4092
       
  • Material Basis Studies of Anti-Influenza A Active Ingredients in Tanreqing
           Injection
    • Authors: Haiyan Zhu; Mingchang Chen, Xunlong Shi, Chenchen Shi, Chenggang Huang
      Abstract: Tanreqing Injection (TRQ) has been used primarily in treating infections of the upper respiratory tract and serious influenza in China, as a classical compound herbal recipe. TRQ had been demonstrated its effects of clearing heat, eliminating phlegm, detoxification, reducing inflammation and alleviating cough. The survival rate, histopathology of lungs and viral titers in mice were evaluated in this study to verify the curative effect of TRQ. However, there is not enough information about the components. In the present study, a high-performance and practical LC/QTOF/MS method was developed for characterization and identification of the natural ingredients in TRQ. A total of 60 compounds, including 10 amino acids, 10 iridoid glucosides, 14 flavonoids, 13 other phenolic compounds, 10 steroid acids and 3 other compounds were characterized and identified. And we confirmed the material basis of Anti-influenza A active ingredients in TRQ. Therefore, we have developed an accurate analytical method. LC/QTOF/MS could be applied for identification the complex components in Traditional Chinese Medicine.
      PubDate: 2017-09-15T15:02:23.487024-05:
      DOI: 10.1002/bmc.4097
       
  • Quantification through TLC-Densitometric analysis, repellency and
           anticholinesterase activity of the homemade extract of Indian cloves
    • Authors: Raphael S. Affonso; Josélia A. Lima, Bruno Lessa, João V.O. Caetano, Marcos T. Obara, Andrea Nóbrega, Eugenie Nepominova, Kamil Musilek, Kamil Kuca, Gláucia Barbosa Candido Alves Slana, Tanos C.C. França
      Abstract: The rise of mosquito's transmitted diseases, like dengue, zika and chikungunya in Brazil in the last years has increased the concerns on protection against mosquito's bites. However, the prohibitive prices of the commercially available repellents for the majority of the Brazilian population, has provoked a search for cheaper solutions, like the use of the homemade ethanolic extract of Indian clove (Syzygium aromaticum L.) as repellent, which has been reported as quite efficient by the local press. In order to verify this, we performed here, the quantification of the main components of this extract through high-performance thin-layer chromatography (HPTLC)-densitometry and evaluated its efficiency as repellent, as well as the acetylcholinesterase (AChE) inhibition capacity. Our results have proved HPTLC-densitometry as an efficient and appropriate method for this quantification and confirmed the repellency activity as well as its capacity of AChE inhibition.
      PubDate: 2017-09-15T01:15:25.985587-05:
      DOI: 10.1002/bmc.4096
       
  • Overcoming interference of plasma phospholipids using HybridSPE for the
           determination of trimetazidine by UPLC-MS/MS
    • Authors: Pravin G. Vanol; Manish Yadav, Mallika Sanyal, Priyanka A. Shah, Pranav S. Shrivastav
      Abstract: An improved, precise and reliable ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed for the quantification of trimetazidine, using trimetazidine-d8 as the internal standard (IS). Interference due to plasma phospholipids during sample preparation was overcome by using hybrid solid phase extraction-phospholipid ultra cartridge. The mean extraction recovery of trimetazidine (98.66 %) and trimetazidine-d8 (97.63 %) from spiked plasma was consistent and reproducible. Chromatographic analysis was performed on UPLC Ethylene Bridged Hybrid (BEH) C18 (50 × 2.1 mm, 1.7 μm) column with isocratic elution using acetonitrile-5 mM ammonium formate, pH 3.5 (40:60, v/v) as the mobile phase. The parent product ion transitions for trimetazidine (m/z 267.1181.1) and trimetazidine-d8 (m/z 275.2181.1) were monitored on a triple quadrupole mass spectrometer with electrospray ionization functioning in the positive multiple reaction monitoring mode. The linearity of the method was established in the concentration range of 0.05-100 ng/mL for trimetazidine. The intra-batch and inter-batch accuracy and precision (% CV) ranged from 97.3-103.1 % and 1.7-5.3 %, respectively. Qualitative and quantitative assessment of matrix effect showed no interference of endogenous/exogenous components. The developed method was used to measure plasma trimetazidine concentration for a bioequivalence study with 12 healthy subjects.
      PubDate: 2017-09-14T06:45:48.483959-05:
      DOI: 10.1002/bmc.4095
       
  • Anti-inflammatory activities and glycerophospholipids metabolism in
           KLA-stimulated RAW 264.7 macrophage cells by diarylheptanoids from the
           rhizomes of Alpinia officinarum
    • Authors: Guogai Zhang; Lifang Zhao, Jiancheng Zhu, Yifan Feng, Xia Wu
      Abstract: Alpinia officinarum was used for anti-inflammatory activity historically in China. Diarylheptanoids isolated from Alpinia officinarum play important biological roles in prevention and treatment of inflammatory disorders. Seven diarylheptanoids (1-7) were isolated from Alpinia officinarum. The cell viabilities and anti-inflammatory activities of diarylheptanoids were evaluated by MTT assay and tumor necrosis factor-a (TNF-a) production in KLA-stimulated RAW 264.7 cells in vitro. Meanwhile, the relationships between their anti-inflammatories and structure-activities were discussed. The result indicated that compounds 1 and 3-7 had significant anti-inflammatory activities. The relationships between inflammation and phospholipids metabolism were elucidated by multivariate data analysis. 22 potential biomarkers were identified in inflammatory group vs. blank group, and 11 potential biomarkers were identified for inflammatory group vs. drug-treatment groups. 10 common phospholipids were characterized. On the basis of previous study in our laboratory, we found that phosphatidylethanolamine (PE, 18:0/18:1) might be the important glycerophospholipid biomarker in inflammation. In this study, we firstly combined anti-inflammatory activities and glycerophospholipids changes of traditional Chinese medicine. And this work suggested that anti-inflammatory activities of diarylheptanoids might be significantly related to glycerophospholipids and could provide a useful data base for investigating anti-inflammatory effects of traditional Chinese medicine.
      PubDate: 2017-09-14T06:10:49.926975-05:
      DOI: 10.1002/bmc.4094
       
  • Intergrated metabonomic study of the effects of Guizhi Fuling capsule
           intervention on primary dysmenorrheal using RP-UPLC-MS complementary with
           HILIC-UPLC-MS technique
    • Authors: Lang Lang; Zhaorui Meng, Lan Sun, Wei Xiao, Longshan Zhao, Zhili Xiong
      Abstract: Guizhi Fuling capsule (GFC), developed from the traditional Chinese prescription of Guizhi Fuling Wan, has been commonly used for the treatment of primary dysmenorrheal (PD). However, the intervention effective mechanism in vivo has not been well elucidated. In this study, an integrated plasma metabonomic strategy based on RP-UPLC-MS coupled with HILIC-UPLC-MS technique has been developed to investigate the global therapeutic effects and intervention mechanisms of Guizhi Fuling capsule (GFC) on dysmenorrhea rats induced by oxytocin. The total twenty potential biomarkers were identified and primarily related to sphingolipid metabolism, steroid hormone biosynthesis, glycerophospholipid metabolism, amino acid metabolism, lipid metabolism and energy metabolism. The results showed that the GFC has therapeutic effects on rat with dysmenorrhea via the regulation of multiple metabolic pathways. Some new potential biomarkers associated with primary dysmenorrhea such as phenylalanine, tryptophan, taurine, carnitine, betaine, creatine and creatinine have been discovered in this study for the first time. This study provides a metabonomic platform based on RP-UPLC-MS complementary with HILIC-UPLC-MS technique to investigate both nonpolar and polar compounds, so as to get a more comprehensive metabolite information for yielding insight into the pathophysiology of PD and assessing the efficacy of GFC on PD rats.
      PubDate: 2017-09-14T04:55:23.511451-05:
      DOI: 10.1002/bmc.4093
       
  • Simultaneous determination of boscalid and fludioxonil in grape and soil
           under field conditions by gas chromatography/tandem triple quadrupole mass
           spectrometry
    • Authors: Haizhen Zhang; A'wei Zhang, Min Huang, Weiwei Yu, Zhurui Li, Sizhuo Wu, Kunming Zhang, Kankan Zhang, Deyu Hu
      Abstract: A gas chromatography–tandem mass spectrometry method was developed and validated to simultaneously determine boscalid and fludioxonil in grape and soil samples. These samples were extracted with 10 mL of acetonitrile and purified using a mixed primary secondary amine/octadecylsilane sorbent. The method showed good linearity (R2>0.99) in the calibration range 0.005–2 μg/mL for both pesticides. The limits of detection and quantification for the two analytes in grape and soil were 0.006 mg/kg and 0.02 mg/kg, respectively. Fungicide recoveries in grape and soil were 81.18–92.11% for boscalid and 82.73–97.67% for fludioxonil with relative standard deviations of 1.31–10.31%. The established method was successfully applied to the residual analysis of boscalid and fludioxonil in real grape and soil samples. The terminal residue concentrations of boscalid and fludioxonil in grape samples collected from Anhui and Guizhou were below 5 mg/kg (the maximum residue limit (MRL) set by China) seven days after the last application and 1 mg/kg (MRL set by USA) 14 days after the last application, respectively. These results could provide guidance for the proper and safe use of boscalid and fludioxonil in grape and help the Chinese government to establish an MRL for fludioxonil in grape.
      PubDate: 2017-09-14T03:56:59.519212-05:
      DOI: 10.1002/bmc.4091
       
  • Bioassay, determination and separation of enantiomers of atenolol by
           direct and indirect approaches using liquid chromatography: A review
    • Authors: Sonika Batra; Ravi Bhushan
      Abstract: Atenolol, a β-adrenergic receptor antagonist, is a chiral compound used for the treatment of cardiovascular diseases and to treat hypertension, coronary heart disease, arrhythmias, sinus tachycardia and myocardial infarction, where it acts preferentially upon the β-adrenergic receptors in the heart. It is marketed as a racemate, but only (S)-enantiomer of (RS)-atenolol is responsible for the β-adrenoceptor blocking activity. Different chromatographic methods have been applied for separation and determination of enantiomers. In this article a review is presented on liquid chromatographic methods for enantioseparation of (RS)-atenolol by both direct and indirect approaches involving practical applications of several chiral stationary phases (CSPs), chiral derivatization reagents, and ligand exchange and impregnation methods. These include methods using both HPLC and TLC for separation, determination and bioassay of enantiomers of atenolol. Besides, some aspects of enantioseparation under achiral phases of liquid chromatography has been briefly mentioned as applicable to (RS)-atenolol. This review provides current available enantioseparation choices not only for (RS)-atenolol but for other applicable racemic drugs.
      PubDate: 2017-09-14T03:07:45.906884-05:
      DOI: 10.1002/bmc.4090
       
  • Issue information
    • Abstract: No abstract is available for this article.
      PubDate: 2017-09-11T01:58:10.044419-05:
      DOI: 10.1002/bmc.3844
       
  • Simultaneous determination of glaucocalyxin A and glaucocalyxin B in rat
           plasma by LC-MS/MS and its application to a pharmacokinetic study after
           oral administration of Rabdosia japonica extract
    • Authors: Weili Huang; Xiaohui Guan, Yongchen Lv
      Abstract: A specific and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for the analysis of glaucocalyxin A and glaucocalyxin B in rat plasma using praeruptorin A as an internal standard. Separation was performed on a Hypurity C18 column (2.1 mm × 50 mm, 5 μm) with isocratic elution using 0.2% formic acid in water-acetonitrile (20:80, v/v). Mass spectrometric detection was conducted using selected reaction monitoring via an electrospray ionization source. Both analytes exhibited good linearity within their concentration ranges (r2> 0.9932). The lower limit of quantitation (LLOQ) of glaucocalyxin A and glaucocalyxin B was1.10 ng/mL. Intra- and inter-day precision exhibited an RSD within 14.5%, and the accuracy (RE) ranged from –12.1% to 15.0% at the LLOQ and three QC levels. The developed assay was successfully applied to a pharmacokinetic study of glaucocalyxin A and glaucocalyxin B in rats after oral administration of Rabdosia japonica extract.
      PubDate: 2017-09-05T17:00:24.483978-05:
      DOI: 10.1002/bmc.4089
       
  • Chromatographic approaches for the characterization and quality control of
           therapeutic oligonucleotide impurities
    • Authors: N.M. El Zahar; N. Magdy, A.M. El-Kosasy, Michael G. Bartlett
      Abstract: Phosphorothioate (PS) oligonucleotides are a rapidly rising class of drugs with significant therapeutic applications. However, due to their complex structure and multi-step synthesis and purification processes, generation of low level impurities and degradation products are common. Therefore, they require significant investment in quality control and impurity identification. This requires the development of advanced methods for analysis, characterization and quantitation. In addition, the presence of the PS linkage leads to the formation of chiral centers which can affect their biological properties and therapeutic efficiency.In this review, the different types of oligonucleotide impurities and degradation products, with an emphasis on their origin, mechanism of formation and methods to reduce, prevent or even eliminate their production, will be extensively discussed. This review will focus mainly on the application of chromatographic techniques to determine these impurities but will also discuss other approaches such as mass spectrometry, capillary electrophoresis and nuclear magnetic resonance spectroscopy. Finally, the chirality and formation of diastereomer mixtures of PS oligonucleotides will be covered as well as approaches used for their characterization and the application for the development of stereochemically-controlled PS oligonucleotides.
      PubDate: 2017-09-04T06:01:06.901561-05:
      DOI: 10.1002/bmc.4088
       
  • Exploring the mechanism of Jieduquyuziyin Prescription on Systemic Lupus
           Erythematosus by GC-MS-based Urine Metabolomics
    • Authors: Jing Wei; Jun Gao, Xinghong Ding
      Abstract: A urine metabolomics method based on gas chromatography mass spectrometry (GC-MS) was developed in order to investigate the metabolites characters of systemic lupus erythematosus (SLE) and therapeutic effects of jieduquyuziyin prescription (JP). The urinary metabolic profiles in urine specimens of the SLE model mice (MRL/lpr) group, prednisone acetate (PA)-treated SLE mice group, JP-treated SLE mice group, and control group (C57BL/6 J) after the administration were analyzed by GC-MS. These metabolic profiles were then processed by multivariate analysis, in particular Mass Profiler Professional (MPP), SIMCA-P and partial least-squares discriminant analysis (PLS-DA). According to the PLS-DA results, the SLE model group and the control group were obviously separated, indicating that the incidence of SLE had a greater impact on the metabolic network, and the SLE model group had significant difference compared with the control group in urine metabolites. 11 differential metabolites were identified to be related to SLE. And the results of differential metabolite identification showed that the metabolites were mainly related to energy metabolism and amino acid metabolism pathway. These results can provide an experimental basis for further exploring the mechanism of traditional Chinese medicine (TCM) in the treatment of SLE.
      PubDate: 2017-09-04T05:40:59.891712-05:
      DOI: 10.1002/bmc.4087
       
  • Ultra performance liquid chromatography-tandem mass spectrometry assay for
           determination of plasma nomegestrol acetate and estradiol in healthy
           postmenopausal women
    • Authors: Sneha G. Nair; Daxesh P. Patel, Mallika Sanyal, Puran Singhal, Pranav S. Shrivastav
      Abstract: A highly sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry method is described for the simultaneous determination of nomegestrol acetate (NOMAC), a highly selective progestogen, and estradiol (E2), a natural estrogen in human plasma. NOMAC was obtained from plasma by solid phase extraction, while E2 was first separated by liquid-liquid extraction with methyl tert-butyl ether followed by derivatization with dansyl chloride. Deuterated internal standards, NOMAC-d5 and E2-d4 were used for better control of extraction conditions and ionization efficiency. The assay recovery of the analytes was within 90-99 %. The analytes were separated on UPLC BEH C18 (50 × 2.1 mm, 1.7 μm) column using a mobile phase comprising of acetonitrile and 3.0 mM ammonium trifluoroacetate in water (80:20, v/v) with a resolution factor (Rs) of 3.21. The calibration curves were linear from 0.01-10.0 ng/mL for NOMAC and 1.00-1000 pg/mL for E2, respectively. The intra-batch and inter-batch precision was ≤5.8 % and the accuracy of quality control samples ranged from 96.7 to 103.4 % for both the analytes. The practical applicability of the method is demonstrated by analyzing samples from 18 healthy postmenopausal women after oral administration of 2.5 mg nomegestrol acetate and 1.5 mg estradiol film coated tablets under fasting.
      PubDate: 2017-09-04T05:26:05.299405-05:
      DOI: 10.1002/bmc.4086
       
  • Metabonomic analysis of serum reveals antifatigue effects of Yi Guan Jian
           on fatigue mice using Gas Chromatography coupled to Mass spectrometry
    • Authors: Sufang Shui; Xiaorong Cai, Rongqing Huang, Bingkun Xiao, Jianyun Yang
      Abstract: Yi Guan Jian (YGJ), one of the most commonly used traditional Chinese medicines (TCM), has been reported to possess significant antifatigue effects in the eastern. However, the mechanisms underlying its antifatigue effects remain largely unresolved. In this study, a metabonomics approach, involving gas chromatography coupled to mass spectrometry (GC/MS) and a multivariate statistical technique, was developed to estimate the extent to which YGJ alleviated the exhausting swimming induced fatigue of mice. High dose treatment with YGJ significantly extended the swimming time of fatigued mice. Significant alterations of metabolites involving amino acids, organic acids and carbohydrates were observed in the serum of fatigued mice, which was reversed by YGJ treatment while biochemical indexes returned to normal. These metabolic changes suggest that the antifatigue effect of YGJ is associated with the impairement of amino acid, organic acids and carbohydrates. It also appears that YGJ can induce significant metabolic alterations independent of the exhausting swimming induced metabolic changes. The significantly altered metabolites induced by YGJ intervention include L-2-Amino-acetoacetate, taurine, fumaric acid, malic acid, oxoadipic acid, L-Aspartate, all of which are associated with antifatigue properties. This suggests that YGJ exerts chemopreventive effects via antifatigue mechanisms.
      PubDate: 2017-09-03T19:45:20.469491-05:
      DOI: 10.1002/bmc.4085
       
  • Development and validation of a simple high-performance liquid
           chromatography analytical method for simultaneous determination of
           phytosterols, cholesterol, and squalene in parenteral lipid emulsions
    • Authors: Ana Novak; Mercè Gutiérrez-Zamora, Lluís Domenech, Josep M. Suñé-Negre, Montserrat Miñarro, Encarna García-Montoya, Josep M. Llop, Josep R. Ticó, Pilar Pérez-Lozano
      Abstract: A simple analytical method for simultaneous determination of phytosterols, cholesterol, and squalene in lipid emulsions was developed due to increased interest in their clinical effects. Method development was based on commonly used stationary (C18, C8 and phenyl) and mobile phases (mixtures of acetonitrile, methanol, and water) under isocratic conditions. Differences in stationary phases resulted in peak overlapping or coelution of different peaks. The best separation of all analyzed compounds was achieved on Zorbax Eclipse XDB C8 (150 x 4.6 mm, 5 μm; Agilent) and ACN/H2O/MeOH = 80:19.5:0.5 (v/v/v). In order to achieve a shorter time of analysis, the method was further optimized and gradient separation was established. The optimized analytical method was validated and tested for routine use in lipid emulsion analyses.
      PubDate: 2017-08-30T08:40:45.82651-05:0
      DOI: 10.1002/bmc.4084
       
  • Simultaneous determination of baicalin, baicalein, wogonoside, wogonin,
           scutellarin, berberine, coptisine, ginsenoside Rb1 and ginsenoside Re of
           Banxia xiexin decoction in rat plasma by LC-MS/MS and its application to a
           pharmacokinetic study
    • Authors: Ying Wang; Yifan Zhang, Juan Xiao, Ranchi Xu, Qiangli Wang, Xinhong Wang
      Abstract: A rapid and high sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for simultaneous determination of nine active constituents, baicalin, baicalein, wogonoside, wogonin, scutellarin, berberine, coptisine, ginsenoside Rb1 and ginsenoside Re in rat plasma after oral administration of Banxia xiexin decoction(BXD). Biological samples were processed wtih acetone-ethyl acetate (4:1, v/v). The mobile phase consisted of methanol and water (containing 0.1% formic acid) with gradient elution at a flow rate of 0.3 mL/min. Detection was performed on a triple quadrupole mass spectrometer using positive ion and negative ESI in the multiple reaction monitoring(MRM) mode. The calibration curves for all analytes had good linearity (r> 0.9933). The mean recovery of all the nine active ingredients was more than 75.2 %, and the intra- and inter-day precisions (RSD) were within 12.0%, the accuracy was between 87.4% and 110.4%. This method was successfully applied to the pharmacokinetic study after administration of BXD. The results of pharmacokinetic study might be helpful for BXD clinical reasonable application and further studies on mechanism.
      PubDate: 2017-08-28T21:40:51.345738-05:
      DOI: 10.1002/bmc.4083
       
  • Investigation on pharmacokinetics, tissue distribution and excretion of
           Schisandrin B in rats by HPLC-MS/MS
    • Authors: Zhuo Wang; Linjun You, Yan Chen, Kaiyong Hu, Zhanbo Wang, Yanan Cheng, Jin Yang, Yong Yang, Guangji Wang
      Abstract: Schisandrin B has received great attention owing to its various biological activities recently. The present study was aimed at the formulation development of schisandrin B and investigating the pharmacokinetic profiles, distribution and excretion of schisandrin B in Sprague-Dawley rats. In this study, micronized schisandrin B particles with particle size of 10~20μm were chosen as the research object. Chromatographic separation was carried out on a BDS HYPERSIL C18 column (50×2.1 mm, I.D. 3.5 μm). Schisandrin B and deoxyschizandrin (internal standard, IS) were detected without interference in the multiple reaction monitoring (MRM) mode with positive electrospray ionization. The pharmacokinetic parameters were calculated by a non-compartmental method. The area under concentration-time curve (AUC0-t) and the maximum concentration (Cmax) showed a significant difference in gender. The calculated absolute oral bioavailability of schisandrin B was approximately 55.0% for female rat and 19.3% for male rat. Schisandrin B exhibited linear pharmacokinetics properties within the range of the tested oral dose (10 mg/kg, 20 mg/kg, 40 mg/kg). After oral administration of schisandrin B, it was extensively distributed in ovary and adipose tissue. The result also showed very low urinary, biliary and fecal excretion of schisandrin B implying that schisandrin B was excreted mainly in the forms of metabolites.
      PubDate: 2017-08-22T01:21:07.467598-05:
      DOI: 10.1002/bmc.4069
       
  • Employment of modified Fe₃O₄ nanoparticles using thermo-sensitive
           polymer for extraction and pre-concentration of cefexime in biological
           samples
    • Authors: Saman Naghibi; Hamed Sahebi
      Abstract: Cefexime as a useful antibiotic can be prescribed to treat infections resulted by bacteria. Nowadays nanoparticles have been widely marked as a universal utopia among many scientists. Variety of researches has been taken place to modify nanoparticles to make them functional as extraction and pre-concentration agents and drug carriers. Temperature-sensitive polymer belongs to a group of substances which perform a gigantic change in their physical features in response to the temperature. Recent polymer can be widely used in different areas, including modification of nanoparticles. In order to modify this nanoparticle, grafting copolymerisation of Fe₃O₄ nanoparticles was done using poly (N-Vinylcaprolactam) and 3-allyloxy-1,2-propanediol. Optimum condition for pre-concentration of cefexime was studied. At this optimum condition, extraction recovery of biological samples in range of 71-89% was obtained. Limit of detection and precision of proposed method was 4.5×10-4 μg.mL-1and less than 4.11% (Relative Standard Deviation) respectively. Based on the results from analysis of cefexime, in biological samples, using proposed method, ability of recent method in extraction and pre-concentration of cefexime was confirmed. Also, satisfaction results from in vitro study of drug release in simulated intestine media was obtained
      PubDate: 2017-08-19T10:45:24.475749-05:
      DOI: 10.1002/bmc.4082
       
  • Quantitative analysis of clofazimine (Lamprene®), an antileprosy agent,
           in human dried blood spots using liquid chromatography-tandem mass
           spectrometry
    • Authors: Wenkui Li; John Doherty, Yunlin Fu, Jimmy Flarakos
      Abstract: An LC-MS/MS method was developed and validated for bioanalysis of clofazimine in human DBS samples in support of a clinical study on multidrug-resistant tuberculosis in developing countries. The validated assay dynamic range was from 10.0 to 2000 ng/mL using a 1/8″ DBS punch. The accuracy and precision of the assay were ±11.0 % (bias) and ≤13.5% (CV) for the LLOQs (10.0 ng/mL) and ± 15% (bias) and ≤ 15% (CV) for all other QC levels. The assay was proved to be free from the possible impact due to spot size and storage temperature (e.g., at 60°C, ≤-60°C). The validated assay is well suited for the intended clinical studies where conventional PK sample collection is not feasible.
      PubDate: 2017-08-19T00:50:18.707133-05:
      DOI: 10.1002/bmc.4068
       
  • Simultaneous determination of morphine-6-D-glucuronide,
           morphine-3-D-glucuronide and morphine in human plasma and urine by
           ultra-performance liquid chromatography-tandem mass spectrometry:
           application to M6G injection pharmacokinetic study.
    • Authors: Wen Xu; Quankun Zhuang, Xia Chen, Ji Jiang, Pei Hu, Hongyun Wang
      Abstract: A robust ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of morphine-6-D-glucuronide (M6G), morphine-3-D-glucuronide (M3G) and morphine (MOR) in human plasma and urine has been developed and validated. The analytes of interest were extracted from plasma by protein precipitation. Urine sample was prepared by dilution. Both plasma and urine samples were chromatographed on an Acquity UPLC HSS T3 column using gradient elution. Detection was performed on a Xevo TQ-S tandem mass spectrometer in multiple reactions monitoring (MRM) mode using positive electrospray ionization (ESI). Matrix interferences were not observed at the retention time of the analytes and internal standard (IS) nalooxone-D5. The lower limit of quantitation (LLOQ) of plasma and urine were 2/0.5/0.5 and 20/4/2 ng/mL for M6G/M3G/MOR, respectively. Calibration curves were linear over the concentration range of 2-2000/0.5-500/0.5-500 and 20-20000/4-4000/2-2000 ng/mL for M6G/M3G/MOR in plasma and urine samples, respectively. The precision was less than 7.14 % and the accuracy was within 85%-115%. Furthermore, stability of the analytes at various conditions, dilution integrity, extraction recovery and matrix effect were assessed. Finally, this quantitative method was successfully applied to the pharmacokinetic study of M6G injection in Chinese non-cancer pain patients.
      PubDate: 2017-08-19T00:20:20.271332-05:
      DOI: 10.1002/bmc.4066
       
  • Application of HPLC-LTQ Orbitrap MS for metabolic profiles of Polygonum
           multiflora extract in rats
    • Authors: Jing Zhang; Tenghua Wang, Zhiyao Ren, Lu Gong, Juan Huang, Junqi Bai, Xiaohui Qiu, Wen Xu
      Abstract: The root of Polygonum multiflora (PM) is an important Chinese herbal medicine for treatment of various diseases. Extensive pharmacological studies have been conducted and demonstrated that it shows a wide range of bioactivities. Meanwhile, considerable amount of hepatotoxicity cases due to oral administration of PM has been reported and attracted great attention. However, The limited knowledge regarding the metabolism of PM restricts the deeper studies on pharmacological/toxic mechanism and therapeutic material basis. The present study was aimed to develop a high-performance liquid chromatography coupled with linear ion trap -Orbitrap hybrid mass spectrometry method for separation and identification of metabolites in rats urine and plasma after oral administration of PM. Based on the proposed strategy, metabolism profiles of PM in rats were proposed for the first time and 43 metabolites were characterized or tentatively identified. The Phase II metabolism such as glucuronidation, and sulfation are the principal pathways of main components. These findings will be beneficial to further understanding of the pharmacological mechanism and pharmacodynamic material basis of Polygonum multiflorum.
      PubDate: 2017-08-17T20:25:33.834292-05:
      DOI: 10.1002/bmc.4067
       
  • LC-ESI-MS/MS determination of 4-methylpyrazole in dog plasma and its
           application to a pharmacokinetic study in dogs
    • Authors: Devaraj V. Chandrasekhar; Suresh P. S, Sreekanth Dittakavi, Rakesh A. Hiremath, Ravi Kanth Bhamidipati, Wolfgang Richter, Nuggehally R. Srinivas, Ramesh Mullangi
      Abstract: A simple, specific, sensitive and rapid LC-ESI-MS/MS method has been developed and validated for the quantification of 4-methylpyrazole in dog plasma using N-methylnicotinamide-d4 as an internal standard (IS) as per regulatory guideline.s Sample preparation was accomplished through a simple protein precipitation. Chromatographic separation of 4-methylpyrazole and the IS was performed on a monolithic (Chromolith RP-18e) column using an isocratic mobile phase comprising 0.2% formic acid in water and acetonitrile (20:80, v/v) at a flow rate of 1.0 mL/min. Elution of 4-methylpyrazole and the IS occurred at ~1.60 and 1.56 min, respectively. The total chromatographic run time was 3.2 min. A linear response function was established in the concentration range of 4.96-4955 ng/mL. The intra- and inter-day accuracy and precision were in the range of 1.81-12.9 and 3.80-11.1%, respectively. This novel method has been applied to a pharmacokinetic study in dogs.
      PubDate: 2017-08-15T11:50:24.743575-05:
      DOI: 10.1002/bmc.4065
       
  • Versatile chromatographic method for catechin determination in development
           of topical formulations containing natural extracts
    • Authors: Ricardo Ferreira-Nunes; Tamara Angelo, Sandra Márcia Mazutti Silva, Pérola Oliveira Magalhães, Tais Gratieri, Marcílio Sérgio Soares Cunha-Filho, Guilherme Martins Gelfuso
      Abstract: Catechin is found in several natural sources, as Eugenia dysenterica and Syzygium cumini extracts. Its antioxidant and UV-protective properties suggest a potential use in cosmetic and dermatological formulations. A simple analytical method capable of giving support to experiments performed along the development of topical formulations containing this natural substance (i.e., drug assay, skin permeation and stability studies), however, is still demanded. Thus, this work aimed to develop and validate a selective HPLC method for catechin determination during the development of topical formulations. Separation was achieved using a RP-C18 column (300 x 3.9 mm; 10 μm), with a mobile phase of methanol/phosphoric acid 0.01 M (15: 85, v/v), flow rate of 0.8 mL/min, temperature set at 40°C, and UV detection at 230 nm. Method was linear in a range from 0.5 to 10.0 μg/mL (r = 0.9998); precise with an overall variation coefficient of 5.5% and accurate with catechin recovery from the skin layers higher than 85%. Additionally, the method was sensitive (limit of detection = 0.109 μg/mL, limit of quantification = 0.342 μg/mL) and selective against plant extracts, skin matrices and formulation interferents, as well as catechin degradation products. It was also robust regarding both methodology parameters and analytical stability.
      PubDate: 2017-08-15T00:35:24.191962-05:
      DOI: 10.1002/bmc.4062
       
  • Sensitive liquid chromatography/tandem mass spectrometry method for the
           determination of two novel highly lipophilic anti-cancer drug candidates
           in rat plasma and tissues
    • Authors: Shirin Hooshfar; Michael R. Linzey, Daqing Wu, Lajos Gera, Kenza Mamouni, Xin Li, Yanhua Chen, Yang Yang, Oluwasegun Olorunyolemi, Michael G. Bartlett
      Abstract: A simple and sensitive liquid chromatography/electrospray ionization tandem mass spectrometry (LC–ESI-MS/MS) method was developed and validated for determination of two highly lipophilic anti-cancer drug candidates, LG1980, and GH501, in rat plasma and tissues (liver, kidney and femur bones).LG1980 and GH501 were extracted from rat plasma and tissue homogenates using liquid–liquid extraction. The method provided a linear range of 1.0–200.0 ng/mL for GH501 in plasma and LG1980 in plasma and liver. For both analytes in other tissue homogenates the linear range was 2.0-400.0 ng/mL. The method was validated with precision within 15% relative standard deviation (RSD), accuracy within 15% relative error (RE) and a consistent recovery. This method has been successfully applied in two preclinical studies for LG1980 and GH501 to determine their concentrations in rat plasma, liver, kidney and bone over 24 h after intravenous injection of compounds.
      PubDate: 2017-08-12T01:55:19.730529-05:
      DOI: 10.1002/bmc.4064
       
  • A proteomics method using immunoaffinity fluorogenic derivatization-liquid
           chromatography/tandem mass spectrometry (FD-LC-MS/MS) to identify a set of
           interacting proteins
    • Authors: Katsunori Nakata; Ryoichi Saitoh, Masaki Ishigai, Kazuhiro Imai
      Abstract: Biological functions in organisms are usually controlled by a set of interacting proteins, and identifying the proteins that interact is useful for understanding the mechanism of the functions. Immunoprecipitation is a method that utilizes the affinity of an antibody to isolate and identify the proteins that have interacted in a biological sample. In this study, the FD-LC-MS/MS method, which involves fluorogenic derivatization followed by separation and quantification by HPLC and finally identification of proteins by HPLC-tandem mass spectrometry, was used to identify proteins in immunoprecipitated samples, using Heat shock protein 90 (HSP90) as a model of an interacting protein in HepaRG cells. As a result, HSC70 protein, which was known to form a complex with HSP90, was isolated, together with three different types of HSP90-beta. The results demonstrated that the proposed immunoaffinity-FD-LC-MS/MS method could be useful for simultaneously detecting and identifying the proteins that interact with a certain protein.
      PubDate: 2017-08-12T01:10:37.545287-05:
      DOI: 10.1002/bmc.4063
       
  • Pharmacokinetics and metabolism of olerciamide A from Portulaca oleracea
           L. in rats by UHPLC-UV and UHPLC-ESI-Q-TOF/MS
    • Authors: Zheming Ying; Cuiyu Li, Mingzhe Gao, Xixiang Ying, Guanlin Yang
      Abstract: The aim of this study was to elucidate the pharmacokinetics of olerciamide A in rats after oral and intravenous administration of P. oleracea L. extract (POE) by a simple and rapid ultra high-performance liquid chromatography (UHPLC) method with bergapten as internal standard (IS). The pharmacokinetic results indicated that olerciamide A was rapidly distributed with Tmax of 30 min after oral administration and presented a low oral absolute bioavailability to be 4.57 %. The metabolism of olerciamide A in rats was also investigated using ultra-high performance liquid chromatography electrospray coupled with quadrupole-time of flight mass spectrometry (UHPLC-ESI-Q-TOF/MS) to elucidate the reason of the low absolute bioavailability of olerciamide A and 7 metabolites of oleraciamide A were found in rat plasma and urine.
      PubDate: 2017-08-12T00:55:24.096787-05:
      DOI: 10.1002/bmc.4061
       
  • Identification of the constituents and metabolites in rats after oral
           administration of Zi Shen Formula by UPLC-Q-TOF/MS combined pattern
           recognition analysis
    • Authors: Yanchao Zheng; Yidan Zhang, Shihan Geng, Mengxi Xu, Qingshen Yin, Lili Song, Pengwei Zhuang, Yanjun Zhang
      Abstract: An ultra high-performance liquid chromatography mass spectrometry method was established to detect and identify the chemical constituents of Zi Shen Formula (ZSF) and its metabolites in serum, urine and feces, after oral administration into rats. A total of 68 compounds were characterized in ZSF extracts. In vivo, 38 prototype components and 32 metabolites of ZSF were tentatively identified in rat serum, urine and feces. 7 metabolic pathways including demethylation, hydroxylation, oxidation, sulfation, glucuronidation, methylation, de-caffeoyl were proposed to involve in the generation of these metabolites. It was found that glucuronidation, methylation and demethylation were the major metabolic processes of alkaloids, while demethylation, methylation, sulfation and de-caffeoyl were the major metabolic pathways of Phenylethanoid glycosides(PhGs). The main metabolic pathways of steroidal saponins were oxidation and isotype reactions. These findings are significant for our understanding of the metabolism of ZSF. The results proposed metabolic pathways of bioactive components might be crucial for further studies of the mechanisms of action and pharmacokinetic evaluations of ZSF.
      PubDate: 2017-08-09T12:50:23.669034-05:
      DOI: 10.1002/bmc.4060
       
  • Qualitative Analysis of Psoraleae Fructus by HPLC-DAD/TOF-MS Fingerprint
           and Quantitative Analysis of Multi-components by Single Marker
    • Authors: Lianjun Luan; Xiaoyu Shen, Xuesong Liu, Yongjiang Wu, ManliangTan
      Abstract: A variety of bioactive substances may account for the recognized efficacy and wide clinical application of Psoraleae Fructus in China. A high performance liquid chromatography-diode array detector (HPLC-DAD) fingerprint method was developed to present the comprehensive phytochemical profile of the crude drug. Thirteen major compounds were separated and identified by high performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC/TOF-MS), namely psoralenoside (PO), isopsoralenoside (IPO), psoralen (PS), isopsoralen (IPS), neobavaisoflavone (NBF), bavachin (BC), corylin (CN), bavachromene (BCM), psoralidin (PD), isobavachalcone (IBC), bacachinin (BCN), corylifol A (CA), bakuchiol (BK). Then quantitative analysis of multi-components by single marker (QAMS) was applied in content determination of PO, IPO, PS, IPS, BC, IBC, BCN, CA and BK, with NBF as the internal standard. The calculation results indicated no significant difference with that by the traditional external standard method (P>0.05, RSD
      PubDate: 2017-08-04T14:40:27.736073-05:
      DOI: 10.1002/bmc.4059
       
  • High-performance liquid chromatography–tandem mass spectrometry for
           simultaneous determination of raltegravir, dolutegravir, and elvitegravir
           concentrations in human plasma and cerebrospinal fluid samples
    • Authors: Kiyoto Tsuchiya; Mayu Ohuchi, Naoe Yamane, Hiroaki Aikawa, Hiroyuki Gatanaga, Shinichi Oka, Akinobu Hamada
      Abstract: A simple sample treatment procedure and sensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) method were developed for the simultaneous quantification of the concentrations of human immunodeficiency virus-1 (HIV-1) integrase strand transfer inhibitors (INSTIs); raltegravir (RAL), dolutegravir (DTG), and elvitegravir (EVG); in human plasma and cerebrospinal fluid (CSF). Plasma and CSF samples (20 μL each) were deproteinized with acetonitrile. Raltegravir-d3 was used as the internal standard (IS). Chromatographic separation was achieved on an XBridge C18 column (50 mm × 2.1 mm i.d., particle size 3.5 μm) using acetonitrile/water (7:3, v/v) containing 0.1% formic acid as the mobile phase at a flow rate of 0.2 mL/min. The run time was 5 min. Calibration curves for all three drugs were linear in the range 5–1500 ng/mL for plasma and 1–200 ng/mL for CSF. The intra- and inter-day precision and accuracy of all three drugs in plasma were coefficient of variation (CV)
      PubDate: 2017-07-31T20:00:36.077881-05:
      DOI: 10.1002/bmc.4058
       
  • Multi-components determination of traditional Chinese medicine preparation
           Yin-zhi-huang injection by LC-MS/MS for screening of its potential
           bioactive candidates using HepaRG cells
    • Authors: Zhi Rao; Fan Zhang, Xiao-yi Zhang, Guo-qiang Zhang, Yan-rong Ma, Yan Zhou, Hong-yan Qin, Xin-an Wu, Yu-hui Wei
      Abstract: Yin-zhi-huang (YZH) injection is an injectable multi-herbal prescription derived from the ancient Chinese medicine formula of Yin-chen-hao-tang, which is widely used in the clinic for the treatment of jaundice and chronic liver diseases. To date, the systematic study of the components in this multi-herbal prescription is still challenged by desirable analytical methods, by which a big array of components could be simultaneously detected at low concentrations. Herein, a new liquid chromatography- tandem mass spectrometry (LC-MS/MS) method by using dynamic multiple reaction monitoring (DMRM) mode was developed to determine multiple peaks in traditional Chinese medicine (TCM) preparation YZH injection. This simple, selective and sensitive method enabled the quantification of 22 components with standard materials with the lower limit of quantification (LLOQ) of 1.46-12.5 ng/mL in cell lysates. This method was successfully applied to celluar uptake and/or binding investigation of components in YZH injection. The results indicated that this strategy might be a useful approach for rapidly screening of the potential bioactive candidates from YZH injection, and the discovered candidates would be used to investigate the pharmacodynamics in the further study.
      PubDate: 2017-07-29T09:05:57.134009-05:
      DOI: 10.1002/bmc.4057
       
  • sQuantification of free fatty acids in human stratum corneum using tandem
           mass spectrometry and surrogate analyte approach
    • Authors: Irena Dapic; Renata Kobetic, Lidija Brkljacic, Sanja Kezic, Ivone Jakasa
      Abstract: The free fatty acids (FFAs) are one of the major components of the lipids in the stratum corneum (SC), the uppermost layer of the skin. Relative composition of FFAs has been proposed as a biomarker of the skin barrier status in patients with atopic dermatitis (AD). Here, we developed LC-ESI-MS/MS method for simultaneous quantification of a range of FFAs with long and very-long chain length in the SC collected by an adhesive tape (D-Squame). Method based on derivatization with 2-bromo-1-methylpyridinium iodide (BMP) and 3-carbinol-1-methylpyridinium iodide (CMP) allowed highly sensitive detection and quantification of FFAs using multiple reaction monitoring (MRM). For the quantification, we applied a surrogate analyte approach and internal standardization using isotope labeled derivatives of FFAs. Adhesive tapes showed presence of several FFAs, which are also present in the SC, a problem encountered in previous studies. Therefore, the levels of FFAs in the SC were corrected by using C12:0 which was present on the adhesive tape, but not detected in the SC. Method was applied on the SC samples of patients with AD and healthy subjects. Quantification using MRM allowed sufficient sensitivity to analyze FFAs of chain lengths C16-C28 in the SC collected in only one tape strip.
      PubDate: 2017-07-29T00:35:25.836762-05:
      DOI: 10.1002/bmc.4056
       
  • 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
           analysis
    • 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
       
  • 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
           cancer
    • 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
           agent
    • 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
       
  • FAST ULTRA HIGH PERFORMANCE LIQUID CHROMATOGRAPHY WITH DIODE ARRAY AND
           MASS SPECTROMETRY METHOD FOR DETERMINATION OF TADALAFIL DRUG SUBSTANCE AND
           ITS IMPURITIES
    • 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
       
  • 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 Sieb.et 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
           cardiotoxicity
    • 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
       
  • 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: The aim of this study was to develop and validate fully the liquid chromatography–tandem mass spectrometry 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. The chromatographic separation was made with Zorbax Eclipse XDB-C18 column (4.6 × 150 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. Satisfactory 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. To the best of our knowledge this is the first liquid chromatography–tandem mass spectrometry method for free MPA monitoring using MPA-d3 that allows to measure plasma ultrafiltrate concentrations as low as 1 ng/mL.
      PubDate: 2017-05-21T21:05:29.94295-05:0
      DOI: 10.1002/bmc.3976
       
  • Screening and identification of multiple constituents and their
           metabolites of Zhi-zi-chi decoction in rat urine and bile by
           ultra-high-performance liquid chromatography quadrupole time-of-flight
           mass spectrometry
    • 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 time-of-flight mass spectrometry. The novel approach of an online data acquisition method dependent on multiple mass defect filter and dynamic background subtraction is combined with multiple data processing techniques. First, 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 were, 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: 2017-05-21T20:50:29.054704-05:
      DOI: 10.1002/bmc.3978
       
  • Ultra-high pressure liquid chromatography–tandem mass spectrometry
           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 dipeptidyl peptidase-4 inhibitor used for the treatment of type 2 diabetes. In this work, a sensitive and selective ultra-high pressure liquid chromatography tandem mass spectrometry method was developed and validated for the determination of omarigliptin in rat plasma. Sample preparation was performed by protein precipitation with acetonitrile. Chromatographic separation of analytes was achieved on an RRHD Eclipse Plus C18 column (2.1 × 50 mm, 1.8 μm), 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 the internal standard. The total run time was 4 min. Retention time of omarigliptin and internal standard was 1.25 and 2.12 min, respectively. Relative standard deviation (%) 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 2–5000 ng/mL with good linearity. The lower limit of quantification and limit of detection of omarigliptin were 2 and 0.25 ng/mL, respectively. Mean recoveries were in the range 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: 2017-05-12T00:24:53.409862-05:
      DOI: 10.1002/bmc.3975
       
  • Use of liquid chromatography hybrid triple-quadrupole mass spectrometry
           for the detection of emodin metabolites in rat bile and urine
    • 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. Owing 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 included four phase I and 18 phase II metabolites. The major metabolites in rat biosamples 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 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: 2017-05-09T01:55:24.618931-05:
      DOI: 10.1002/bmc.3979
       
  • 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 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 in 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 × 4.6 mm) column with a gradient mobile phase comprising ammonium acetate containing 0.01% TFA in purified water and acetonitrile. The retention times achieved were 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 multiple reaction monitoring 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 to 500 ng/mL, with a lower limit of quantitation of 1.0 ng/mL and for NDP linearity from 0.1 to 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
      PubDate: 2017-05-07T20:55:29.122596-05:
      DOI: 10.1002/bmc.3967
       
  • 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 analog, (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 an 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. 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 the extracting solvent. The assay was validated by following FDA guidelines and all parameters were found to be within acceptable limits. The linearity was between 10.1 and 2500 ng/mL and the lower limit of quantification was 10.1 ng/mL. The reported results indicate that the assay could meet the requirement for analysis of this compound in 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: 2017-05-07T20:40:25.390865-05:
      DOI: 10.1002/bmc.3981
       
  • A chiral LC-MS/MS method for the enantioselective determination of R-(+)-
           and S-(–)-pantoprazole in human plasma and its application to a
           pharmacokinetic study of S-(–)-pantoprazole sodium injection
    • Authors: Huiwen Jiao; Yueqi Li, Luning Sun, Hongwen Zhang, Liyuan Yu, Lei Yu, Ziqingyun Yuan, Lijun Xie, Juan Chen, Yongqing Wang
      Abstract: Pantoprazole, a proton pump inhibitor, is clinically used for the treatment of peptic diseases. An enantioselective LC-MS/MS method was developed and validated for the simultaneous determination of pantoprazole enantiomers in human plasma. Pantoprazole enantiomers and the internal standard were extracted from plasma using acetonitrile. Chiral separation was carried on a Chiralpak IE column using the mobile phase consisted of 10 mm ammonium acetate solution containing 0.1% acetic acid–acetonitrile (28 : 72, v/v). MS analysis was performed on an API 4000 mass spectrometer. Multiple reactions monitoring transitions of m/z 384.1200.1 and 390.1206.0 were used to quantify pantoprazole enantiomers and internal standard, respectively. For each enantiomer, no apparent matrix effect was found, the calibration curve was linear over 5.00–10,000 ng/mL, the intra- and inter-day precisions were below 10.0%, and the accuracy was within the range of –5.6% to 0.6%. This method was applied to the stereoselective pharmacokinetic studies in human after intravenous administration of S-(–)-pantoprazole sodium injections. No chiral inversion was observed during sample storage, preparation procedure and analysis. While R-(+)-pantoprazole was detected in human plasma with a slightly high concentration, which implied that S-(–)-pantoprazole may convert to R-(+)-pantoprazole in some subjects.
      PubDate: 2017-05-07T20:35:28.036121-05:
      DOI: 10.1002/bmc.3980
       
  • 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
       
  • LC–MS/MS method for simultaneous determination of flavonoids and
           physalins in rat plasma: Application to pharmacokinetic study after oral
           administration of Physalis alkekengi var. franchetii (Chinese lantern)
           extract
    • Authors: Yaqing Guo; Hongxia Liu, Liqin Ding, Mahmood Oppong, Guixiang Pan, Feng Qiu
      Abstract: A rapid and sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of luteolin, luteolin-7-O-β-D-glucopyranoside, physalin A, physalin D and physalin L in rat plasma. Scutellarein and dexamethasone were used as the internal standards (IS). Plasma samples were prepared by liquid-liquid extraction with ethyl acetate. The five constituents were separated on an Acquity UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm). A gradient elution procedure was used with acetonitrile (A)-0.1% aqueous formic acid (B). Mass spectrometric detection was performed in negative ion multiple reaction monitoring mode with an electrospray ionization (ESI) source. This method showed good linearity (r2 > 0.997) over a concentration range of 2.0–500 ng/mL with a lower limit of quantification of 2.0 ng/mL for all five compounds. The inter- and intra-day accuracy ranged from 91.7 to 104%, and precisions (RSD) were 85%. This validated method was successfully applied for the first time to the pharmacokinetic study of five ingredients after oral administration of 70% ethanol extract of Chinese lantern in rats.
      PubDate: 2017-05-02T21:20:32.073055-05:
      DOI: 10.1002/bmc.3970
       
  • The effect of tripterygium glucoside tablet on pharmacokinetics of
           losartan and its metabolite EXP3174 in rats
    • Authors: Yongsheng Hu; Xuexue Zhou, Hui Shi, Wenyu Shi, Shengjie Ye, Hai Zhang
      Abstract: Losartan and tripterygium glucoside tablet (TGT) are often simultaneously used for reducing urine protein excretion in clinic. However, it is unknown whether there is potential herb–drug interaction between losartan and TGT. The aim of this study was to investigate their potential herb–drug interaction, and clarify the mechanism of the effect of TGT on the pharmacokinetics of losartan and its metabolite EXP3174 in rats. The plasma concentrations of losartan and EXP3174 were determined by LC–MS, and the main pharmacokinetic parameters were calculated. The Cmax, t1/2 and AUC(0–t) of losartan became larger after co-administration, while the Cmax and AUC(0–t) of EXP3174 became smaller, suggesting that TGT could influence the pharmacokinetics of losartan and EXP3174. The effects of TGT and its main components on the metabolic rate of losartan were further investigated in rat liver microsomes. Results indicated that TGT and its two main ingredients could decrease the metabolic rate of losartan. Therefore, it was speculated that TGT might increase the plasma concentration of losartan and decrease the concentration of EXP3174 by inhibiting the metabolism of losartan. The results could provide references for clinical medication guidance of losartan and TGT to avoid the occurrence of adverse reactions.
      PubDate: 2017-04-24T20:10:36.4452-05:00
      DOI: 10.1002/bmc.3973
       
  • A simple and cost-effective HPLC-UV method for the detection of
           levetiracetam in plasma/serum of patients with epilepsy
    • Authors: Lynette Engelbrecht; C. J. Grobler, Malie Rheeders
      Abstract: A simple, fast and cost-effective method was developed and validated for the determination of levetiracetam (LEV) in plasma/serum of patients using high performance liquid chromatography (HPLC) with ultraviolet detection. The stability of LEV plasma/serum samples over time and in different blood collection tubes was evaluated. Serum/plasma samples were deproteinized by methanol spiked with the internal standard, gabapentin. HPLC was carried out on a Venusil XBP C18, 250 × 4.6 mm, 5 μm column, at a flow rate of 1.0 mL/min and with mobile phase consisting of 50 mm potassium dihydrogen phosphate–acetonitrile at a pH of 5.5. The UV detector was set at 205 nm and 10 μL was injected. Total runtime was 15 min. Calibration curves were linear (correlation coefficient = 0.999) over a concentration range of 1–60 μg/mL. Relative standard deviation values for both the inter-day and intra-day precision and accuracy were
      PubDate: 2017-04-20T20:52:36.723554-05:
      DOI: 10.1002/bmc.3969
       
  • Simultaneous determination of piperaquine and its N-oxidated metabolite in
           rat plasma using LC-MS/MS
    • Authors: Huixiang Liu; Meitong Zang, Aijuan Yang, Jianbo Ji, Jie Xing
      Abstract: A sensitive and efficient liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous determination of piperaquine (PQ) and its N-oxidated metabolite (PQ-M) in plasma. A simple protein precipitation procedure was used for sample preparation. Adequate chromatographic retention was achieved on a C18 column under gradient elution with acetonitrile and 2 mm aqueous ammonium acetate containing 0.15% formic acid and 0.05% trifluoroacetic acid. A triple-quadrupole mass spectrometer equipped with an electrospray source was set up in the positive ion mode and multiple reaction monitoring mode. The method was linear in the range of 2.0–400.0 ng/mL for PQ and 1.0–50.0 ng/mL for PQ-M with suitable accuracy, precision and extraction recovery. The lower limits of detection (LLOD) were established at 0.4 and 0.2 ng/mL for PQ and PQ-M, respectively, using 40 μL of plasma sample. The matrix effect was negligible under the current conditions. No effect was found for co-administrated artemisinin drugs or hemolysis on the quantification of PQ and PQ-M. Stability testing showed that two analytes remained stable under all relevant analytical conditions. The validated method was successfully applied to a pharmacokinetic study performed in rats after a single oral administration of PQ (60 mg/kg).
      PubDate: 2017-04-19T21:26:04.712425-05:
      DOI: 10.1002/bmc.3974
       
  • Simultaneous determination of wogonin, oroxylin a, schisandrin,
           paeoniflorin and emodin in rat serum by HPLC–MS/MS and application to
           pharmacokinetic studies
    • Authors: Minting Chen; Suying Wei, Chaohua Luo, Feilong Chen, Shuai Song, Qun Shen, Zhixian Mo, Fenghuan Wei
      Abstract: Wogonin and oroxylin A in Scutellariae Radix, schisandrin in Chinensis Fructus, paeoniflorin in Moutan Cortex and emodin in Polygoni Cuspidate Rhizome et Radix are anti-inflammatory active compounds. A method for simultaneous determination of the five compounds in rat was developed and validated using high-performance liquid chromatography with tandem mass spectrometry (HPLC–MS/MS). The separation was performed on a Symmetry C18 column (4.6 × 50 mm, 3.5 μm) with acetonitrile and 0.1% formic acid aqueous solution as the mobile phases. The detection was performed using multiple-reaction monitoring with electrospray ionization source in positive–negative ion mode. The calibration curves showed good linearity (r ≥ 0.9955). The lower limit of quantification (LLOQ) was 5 ng/mL for wogonin and schisandrin, 10 ng/mL for oroxylin A and emodin, and 15 ng/mL for paeoniflorin, respectively. The relative standard deviations of intraday and interday precisions were
      PubDate: 2017-04-19T02:57:06.42337-05:0
      DOI: 10.1002/bmc.3966
       
  • Comparative pharmacokinetic study of pyranocoumarins and khellactone in
           normal and acute lung injury rats after oral administration of Peucedanum
           praeruptorum Dunn extracts using a rapid and sensitive liquid
           chromatography–tandem mass spectrometry method
    • Authors: An Kang; Tong Xie, Dong Zhu, Yu Dong, Hongmei Wen, Yuqiong Pei, Jinjun Shan, Liuqing Di
      Abstract: Pyranocoumarins are the main constitutes in Peucedanum praeruptorum Dunn and possess various biological activities. In this article, we developed and validated a rapid and sensitive liquid chromatography–tandem mass spectrometry method for the targeted quantification of the pyranocoumarins, praeruptorin A, praeruptorin B and praeruptorin E, and khellactone, which is a common metabolite of these pyranocoumarins in rat plasma samples. We then performed a comparative pharmacokinetic study of these pyranocoumarins and khellactone in normal and lipopolysaccharide-induced acute lung injury (ALI) in rats following oral administration of P. praeruptorum Dunn extracts. Calibration curves gave desirable linearity (r > 0.99) and the lower limit of quantifications were sufficient for quantitative analysis. The precision and accuracy were assessed by intra-batch and inter-batch assays, and the relative standard deviations were all within 10.23% and the accuracy (relative error) was between −5.52% and 8.68%. The extraction recoveries, matrix effects and stability were also acceptable. The pharmacokinetic study revealed that the area under the concentration–time curve (0–t) of khellactone in ALI rats was significantly decreased compared with the normal rats. Meanwhile, the systemic exposures of these pyranocoumarins were slightly higher in the ALI rats than those in normal rats were. The pharmacokinetic study in the pathological state might provide information that was more comprehensive to guide the clinical usage of P. praeruptorum Dunn.
      PubDate: 2017-04-18T19:40:35.100083-05:
      DOI: 10.1002/bmc.3977
       
  • A novel assay to determine acetylcholinesterase activity: The application
           potential for screening of drugs against Alzheimer's disease
    • Authors: Liang Peng; Zhengxing Rong, Hao Wang, Biyun Shao, Lei Kang, Hong Qi, Hongzhuan Chen
      Abstract: Acetycholinesterase (AChE) that regulates hydrolysis of acetylcholine (ACh) in the brain, is an important target for treatment of Alzheimer's disease (AD), a feature of which is ACh deficiency. However, the methods to precisely determine AChE activity are still under development. We developed a new method to exploit acetylcholine-d4 as a surrogate substrate of ACh and measure product choline-d4 via liquid chromatography–tandem mass spectrometry (LC–MS/MS). This assay detected activity of AChE present in the normal mouse brain, which is consistent with the standard Ellman assay that determines products spectrophotometrically. In AD mouse models, the result of LC–MS/MS assay showed significant higher AChE activity than that seen in control normal mice, while treatment of AD mice with an AChE inhibitor, huperzine A, led to partial decreases in AChE activity. Our results suggest that this surrogate-based LC–MS/MS method is a new, sensitive and convenient assay for the determination of AChE activity, providing a useful means for screening active compounds that target AChE.
      PubDate: 2017-04-18T02:55:57.839899-05:
      DOI: 10.1002/bmc.3971
       
  • Development of an LC–MS/MS method for quantification of two pairs of
           isomeric flavonoid glycosides and other ones in rat plasma: Application to
           pharmacokinetic studies
    • Authors: Sixi Zhang; Yang Xie, Jing Wang, Yanmei Geng, Yu Zhou, Chengxin Sun, Guangshu Wang
      Abstract: A liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for simultaneous determination of six flavonoid glycosides – isoorientin (1), orientin (2), 2″-O-β-d-xylopyranosyl isoorientin (3), 2″-O-β-d-xylopyranosyl isovitexin (4), 6-C-l-α-arabipyranosyl vitexin (5) and vitexin (6) – in rat plasma using isoquercitrin as the internal standard (IS). Plasma samples were prepared by a one-step protein precipitation with acetonitrile. Chromatographic analysis was carried out on a 25 cm C18 column with a gradient mobile phase consisting of acetonitrile and 0.1% aqueous formic acid. Six analytes and IS were detected through electrospray ionization in negative-ion selection reaction monitoring mode. The mass transitions were as follows: m/z 447.2  327.0 for 1, m/z 447.2  327.0 for 2, m/z 579.3  458.9 for 3, m/z 563.0  293.1 for 4, m/z 563.0  353.0 for 5, m/z 431.1  311.1 for 6, and m/z 463.1  300.2 for IS. Calibration curves exhibited good linearity (r2 > 0.9908) over a wide concentration range for all compounds. Intra- and inter-day precision (RSD, %) at four different levels were both
      PubDate: 2017-04-16T20:30:30.923644-05:
      DOI: 10.1002/bmc.3972
       
  • Development and validation of an HPLC-UV method for the simultaneous
           determination of the antipsychotics clozapine, olanzapine and quetiapine,
           several beta-blockers and their metabolites
    • Authors: Margarete Silva Gracia; Alexandra Köppl, Sandra Unholzer, Ekkehard Haen
      Abstract: A simple, accurate and selective column-switching high-performance liquid chromatography (HPLC) method was developed and validated for simultaneous quantification of six beta-blockers (metoprolol, timolol, bisoprolol, propranolol, carvedilol and nebivolol), three of their metabolites (α-hydroxy metoprolol, N-desisopropyl propranolol and 4′-hydroxy carvedilol 4-HCAR), three antipsychotics (olanzapine, clozapine and quetiapine) and three of their metabolites (N-desmethyl olanzapine, N-desmethyl clozapine and N-desalkyl quetiapine) in human serum. After pretreatment on a Merck LiChrospher RP-4 ADS column (25 μm), drugs were separated on a Phenomenex Gemini Phenyl Hexyl 110 A column (250 × 4.6 mm, 5 μm) using a gradient mixture of acetonitrile and potassium dihydrogen phosphate buffer pH 3.1 (containing 10% methanol) as a mobile phase at a flow rate of 1 mL/min. The total analysis time was 40 min. For detection of the analytes, four different UV wavelengths were used: 215, 226, 242 and 299 nm. The method was validated according to the guidelines of the Society of Toxicology and Forensic Chemistry in terms of selectivity, linearity, accuracy, precision and stability and successfully applied for the analysis of the 15 described analytes in human serum.
      PubDate: 2017-04-03T23:05:35.617911-05:
      DOI: 10.1002/bmc.3968
       
  • Sensitive quantification of coixol, a potent insulin secretagogue, in
           Scoparia dulcis extract using high-performance liquid chromatography
           combined with tandem mass spectrometry and UV detection
    • Authors: Arslan Ali; Faraz Ul Haq, Qamar Arfeen, Khaga Raj Sharma, Achyut Adhikari, Syed Ghulam Musharraf
      Abstract: Diabetes is a major global health problem which requires new studies for its prevention and control. Scoparia dulcis, a herbal product, is widely used for treatment of diabetes. Recent studies demonstrate coixol as a potent and nontoxic insulin secretagog from S. dulcis. This study focuses on developing two quantitative methods of coixol in S. dulcis methanol-based extracts. Quantification of coixol was performed using high-performance liquid chromatography–tandem mass spectrometry (method 1) and high-performance liquid chromatography–ultraviolet detection (method 2) with limits of detection of 0.26 and 11.6 pg/μL, respectively, and limits of quantification of 0.78 and 35.5 pg/μL, respectively. S. dulcis is rich in coixol content with values of 255.5 ± 2.1 mg/kg (method 1) and 220.4 ± 2.9 mg/kg (method 2). Excellent linearity with determination coefficients>0.999 was achieved for calibration curves from 10 to 7500 ng/mL (method 1) and from 175 to 7500 ng/mL (method 2). Good accuracy (bias < −8.6%) and precision (RSD 
      PubDate: 2017-03-21T20:50:40.018083-05:
      DOI: 10.1002/bmc.3964
       
  • Dissipation kinetics and pre-harvest residue limit of pyriofenone in
           oriental melon (Cucumis melo Var. makuwa) grown under regulated climatic
           conditions
    • Authors: Hyung Suk Chung; Md. Humayun Kabir, A.M. Abd El-Aty, Han Sol Lee, Md. Musfiqur Rahman, Byung-Joon Chang, Ho-Chul Shin, Jae-Han Shim
      Abstract: A high-performance liquid chromatography–ultraviolet detection was used to estimate the disappearance rates as well as the pre-harvest residue limits of pyriofenone in oriental melon (Cucumis melo var. makuwa) grown under greenhouse conditions in two different locations (A and B) in Seongju, Republic of Korea. The identity of the compound in standard solution and representative field incurred samples was confirmed using liquid chromatography–tandem mass spectrometry. The method was validated in terms of linearity, limits of detection and quantification, accuracy (expressed as recovery) and precision (expressed as relative standard deviation) for accurate and precise quantitation. Notably, the residual levels of field incurred samples collected over days 0–10 post-application were below the maximum residue level (0.2 mg/kg) established by the Korean Ministry of Food and Drug Safety. Site A showed lower residue levels and a higher decline rate than site B, which might be attributed to seasonal variation (high temperature) and increased metabolic and enzyme profiling in the mature fruits. The half-lives were similar, 4.9 and 4.3 days, at sites A and B, respectively. Using the pre-harvest residue limit, we predicted the residue amounts at 10 and 5 days before harvest, which resulted in concentrations lower than the provisional maximum residue level at harvest time.
      PubDate: 2017-03-21T20:42:33.992654-05:
      DOI: 10.1002/bmc.3965
       
 
 
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