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![]() ![]() ![]() ![]() |
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 |
DOI | 10.1016/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
浏览0
下载0
收藏0
其他版本
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。