中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Qualitative and quantitative determination of anaprazole and its major metabolites in human plasma

文献类型:期刊论文

作者Tang, Chongzhuang1,2; Li, Liang1; Ma, Xifeng3; Wang, Jin3; Chen, Bo3; Dai, Xiaojian1; Zhang, Yifan1; Chen, Xiaoyan1,2
刊名JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
出版日期2020-05-10
卷号183页码:10
关键词Metabolite identification LC-MS/MS UPLC-UV/Q-TOF Anaprazole
ISSN号0731-7085
DOI10.1016/j.jpa.2020.113146
通讯作者Chen, Xiaoyan(xychen@simm.ac.cn)
英文摘要Anaprazole is a novel proton pump inhibitor under development for the treatment of gastric and duodenal ulcers. In the present study, an ultra-performance liquid chromatography-ultraviolet detector/quadrupole time-of-flight mass spectrometry method was developed for the metabolic profiling of human plasma after an oral administration of 40 mg anaprazole. The principal metabolic pathways were identified as sulfoxide reduction to thioether (M8-1), dehydrogenation (M21-1), sulfoxide oxidation to sulfone (M16-3), and sulfoxide reduction with O-demethylation to form carboxylic acid (M7-1). Anaprazole, M8-1, M16-3, M21-1, and M7-1 were selected and further quantified in human plasma by using a rapid and sensitive liquid chromatography-tandem mass spectrometry method. Anaprazole and its four metabolites were extracted from 50 of pi plasma by acetonitrile protein precipitation. Chromatographic retention and separation were achieved on an Kinetex XB-C-18 column (50 mm x 4.6 mm i.d., 5 mu m) under gradient elution using 5 mM ammonium acetate with 0.005 % ammonium hydroxide and methanol with 0.005 % ammonium hydroxide as the mobile phase. Positive electrospray ionization was performed using multiple reaction monitoring with transitions of m/z 402.2 -> 242.2, 386.2 -> 226.2, 400.2 -> 242.2, 418.2 -> 282.2, and 386.2 -> 161.2 for anaprazole, M8-1, M21-1, M16-3, and M7-1, respectively. This method was linear in the range of 5.00-3000 ng/mL for anaprazole and 1.00-600 ng/mL for the four metabolites. The lower limit of quantitation was established at 5.00 ng/mL for anaprazole and 1.00 ng/mL for the metabolites. The quantitative method was used to evaluate the pharmacokinetics of anaprazole in phase I clinical trials. (C) 2020 Elsevier B.V. All rights reserved.
WOS关键词PROTON PUMP INHIBITORS ; PERFORMANCE LIQUID-CHROMATOGRAPHY ; RABEPRAZOLE ; OMEPRAZOLE ; LANSOPRAZOLE ; THIOETHER
资助项目National Natural Science Foundation of China[81573500] ; National Natural Science Foundation of China[81573351]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000527293500012
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/280431]  
专题中国科学院上海药物研究所
通讯作者Chen, Xiaoyan
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China
2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
3.XuanZhu Pharma, 2518 Tianchen St, Jinan, Shandong, Peoples R China
推荐引用方式
GB/T 7714
Tang, Chongzhuang,Li, Liang,Ma, Xifeng,et al. Qualitative and quantitative determination of anaprazole and its major metabolites in human plasma[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2020,183:10.
APA Tang, Chongzhuang.,Li, Liang.,Ma, Xifeng.,Wang, Jin.,Chen, Bo.,...&Chen, Xiaoyan.(2020).Qualitative and quantitative determination of anaprazole and its major metabolites in human plasma.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,183,10.
MLA Tang, Chongzhuang,et al."Qualitative and quantitative determination of anaprazole and its major metabolites in human plasma".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 183(2020):10.

入库方式: OAI收割

来源:上海药物研究所

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