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Simultaneous determination of metacavir and its metabolites in rat plasma using high‐performance liquid chromatography with tandem mass spectrometric detection (LC‐MS/MS)
Author(s) -
Zhang Yue,
Huang Xin,
Jiang Zhenzhou,
Huang Xiao,
Hu Yue,
Zhu Dan,
Zhang Shuang,
Wang Jiaying,
Zhang Luyong
Publication year - 2012
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.1667
Subject(s) - chemistry , chromatography , selected reaction monitoring , analyte , tandem mass spectrometry , liquid chromatography–mass spectrometry , mass spectrometry , extraction (chemistry) , high performance liquid chromatography , pharmacokinetics , matrix (chemical analysis) , analytical chemistry (journal) , medicine
A sensitive and selective liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method for the simultaneous determination of metacavir and its two metabolites in rat plasma was developed and validated. Tinidazole was used as an internal standard and plasma samples were pretreated with one‐step liquid–liquid extraction. In addition, these analytes were separated using an isocratic mobile phase on a reverse‐phase C 18 column and analyzed by MS in the selected reaction monitoring mode. The monitored precursor to product‐ion transitions for metacavir, 2′,3′‐dideoxyguanosine, O ‐methylguanine and the internal standard were m / z 266.0 → 166.0, m / z 252.0 → 152.0, m / z 166.0 → 149.0 and m / z 248.0 → 202.0, respectively. The standard curves were found to be linear in the range of 1–1000 ng/mL for metacavir, 5–5000 ng/mL for 2′,3′‐dideoxyguanosine and 1–1000 ng/mL for O ‐methylguanine in rat plasma. The precision and accuracy for both within‐ and between‐batch determination of all analytes ranged from 2.83 to 9.19% and from 95.86 to 111.27%, respectively. No significant matrix effect was observed. This developed method was successfully applied to an in vivo pharmacokinetic study after a single intravenous dose of 20 mg/kg metacavir in rats. Copyright © 2011 John Wiley & Sons, Ltd.