Abstract
A highly sensitive and rapid liquid chromatography–tandem mass spectrometry method was developed and validated for the determination of artemether and its metabolite dihydroartemisinin in human plasma using artemisinin as an internal standard. Chromatographic separation was achieved on a Supelco Discovery HS C18 RP column (150 mm × 4.6 mm, 5 µm; Bellefonte, USA) using acetonitrile and water with 0.1 % formic acid (80:20, v/v) as a mobile phase in isocratic mode. A high-resolution Thermo Electron Corporation LTQ-Orbitrap mass spectrometer (San Jose, USA) was used in single ion monitoring (SIM) mode using atmospheric pressure chemical ionization (APCI) as an interface. The following extracted ion ranges ([M + H]+) were monitored: m/z 267.14–267.16 for artemether, m/z 221.16–221.18 for dihydroartemisinin and m/z 283.14–283.16 for internal standard. The limit of detection (LOD) and limit of quantification (LOQ) for artemether were 0.3 and 0.8 ng mL−1, while for dihydroartemisinin were 0.2 and 0.6 ng mL−1, respectively. The validated method was successfully applied to the quantification of artemether and dihydroartemisinin in plasma samples of healthy volunteers participating in pharmacokinetic drug–food interaction studies.
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Acknowledgments
The authors are grateful to the University of Peshawar for funding this research project. Novartis Pharma is acknowledged for kind donation of artemether and dihydroartemisinin.
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The clinical trials were conducted according to the guidelines of “World Medical Associations, Declaration of Helsinkiethical principles for medical research involving human subjects” and were approved by the Ethics Committee of the Department of Pharmacy, University of Peshawar (Trial number 02/EC-12/Pharm).
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A written informed consent was obtained from all the participants enrolled in the study.
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Khuda, F., Iqbal, Z., Shah, Y. et al. A High-Resolution LC–MS/MS Method for the Quantitative Determination of Artemether and Its Metabolite Dihydroartemisinin in Human Plasma and Its Application to Pharmacokinetic Studies. Chromatographia 79, 609–618 (2016). https://doi.org/10.1007/s10337-016-3064-6
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DOI: https://doi.org/10.1007/s10337-016-3064-6