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Qualitative–(semi)quantitative data acquisition of artemisinin and its metabolites in rat plasma using an LTQ/Orbitrap mass spectrometer
Author(s) -
Du Fuying,
Liu Tian,
Shen Tao,
Zhu Fanping,
Xing Jie
Publication year - 2012
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.2958
Subject(s) - chemistry , orbitrap , chromatography , protein precipitation , mass spectrometry , electrospray ionization , pharmacokinetics , analyte , selected reaction monitoring , metabolite , resolution (logic) , analytical chemistry (journal) , tandem mass spectrometry , pharmacology , biochemistry , medicine , artificial intelligence , computer science
Artemisinin (QHS) is one of the first‐line antimalarials, and autoinduction of CYP‐mediated metabolism can result in its reduced exposure. To better understand the autoinduction of QHS, we evaluated the pharmacokinetics of QHS and its phase I metabolites in rats using an liquid chromatography‐high resolution mass spectrometry (LC‐HRMS) method. The LC separation was improved, allowing the separation of QHS and its metabolites from their diastereomers, and seven metabolites of QHS with relatively high exposure were identified in rat plasma, including deoxyartemisinin (DQHS), three monoyhydroxylated plus deoxyl metabolites (M1–M3) and three monohydroxylated metabolites (M4–M6). For detection, a high‐resolution LTQ/Orbitrap mass spectrometer with an electrospray ionization (ESI) inlet in the positive ion mode was used. High‐resolution extracted ion chromatograms for each analyte were obtained by processing the full‐scan MS dataset with 10 ppm mass tolerance. The plasma samples were pretreated by protein precipitation with acetonitrile. The standard curve was linear ( r 2 > 0.99) over the QHS and DQHS concentration range of 5.0–200.0 ng/ml in 50 µl of plasma, which offered sufficient sensitivity and accuracy for the determination of QHS and its metabolites. A 3‐day validation approach was used for absolute quantitation of QHS and DQHS. The other six metabolites of QHS were semiquantified based on the calibration curve of QHS. The present method was applied to the pharmacokinetic study of QHS in rats after a single oral administration. The data shown here also suggest that this type of mass analyzer will be capable of a quantitative–qualitative workflow. Copyright © 2012 John Wiley & Sons, Ltd.