标题:Metabolite identification of the antimalarial piperaquine in vivo using liquid chromatography-high-resolution mass spectrometry in combination with multiple data-mining tools in tandem
作者:Yang, Aijuan; Zang, Meitong; Liu, Huixiang; Fan, Peihong; Xing, Jie
作者机构:[Yang, Aijuan; Zang, Meitong; Liu, Huixiang; Fan, Peihong; Xing, Jie] Shandong Univ, Sch Pharmaceut Sci, Jinan, Peoples R China.
通讯作者:Xing, J
通讯作者地址:[Xing, J]Shandong Univ, Sch Pharmaceut Sci, Jinan, Peoples R China.
来源:BIOMEDICAL CHROMATOGRAPHY
出版年:2016
卷:30
期:8
页码:1324-1330
DOI:10.1002/bmc.3689
关键词:piperaquine; metabolites; liquid chromatography tandem high-resolution; mass spectrometry; mass defect filter; isotope pattern filter
摘要:Artemisinin-based combination therapy is widely used for the treatment of uncomplicated Plasmodium falciparum malaria, and piperaquine (PQ) is one of important partner drugs. The pharmacokinetics of PQ is characterized by a low clearance and a large volume of distribution; however, metabolism of PQ has not been thoroughly investigated. In this work, the metabolite profiling of PQ in human and rat was studied using liquid chromatography tandem high-resolution LTQ-Orbitrap mass spectrometry (HRMS). The biological samples were pretreated by solid-phase extraction. Data processes were carried out using multiple data-mining techniques in tandem, i.e., isotope pattern filter followed by mass defect filter. A total of six metabolites (M1-M6) were identified for PQ in human (plasma and urine) and rat (plasma, urine and bile). Three reported metabolites were also found in this study, which included N-oxidation (M1, M2) and carboxylic products (M3). The subsequent N-oxidation of M3 resulted in a new metabolite M4 detected in urine and bile samples. A new metabolic pathway N-dealkylation was found for PQ in human and rat, leading to two new metabolites (M5 and M6). This study demonstrated that LC-HRMSn in combination with multiple data-mining techniques in tandem can be a valuable analytical strategy for rapid metabolite profiling of drugs. Copyright (c) 2016 John Wiley & Sons, Ltd.
收录类别:SCOPUS;SCIE
WOS核心被引频次:4
Scopus被引频次:5
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84977589514&doi=10.1002%2fbmc.3689&partnerID=40&md5=d30f0bbbf73ea19b5141fda61b261b65
TOP