Metabolite identification of the antimalarial piperaquinein vivousing liquid chromatography-high-resolution mass spectrometry in combination with multiple data-mining tools in tandem

Autor: Meitong Zang, Huixiang Liu, Jie Xing, Peihong Fan, Aijuan Yang
Rok vydání: 2016
Předmět:
Zdroj: Biomedical Chromatography. 30:1324-1330
ISSN: 0269-3879
DOI: 10.1002/bmc.3689
Popis: 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-HRMS(n) in combination with multiple data-mining techniques in tandem can be a valuable analytical strategy for rapid metabolite profiling of drugs. Copyright © 2016 John Wiley & Sons, Ltd.
Databáze: OpenAIRE
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