title: Simultaneous determination of metacavir and its metabolites in rat plasma using high-performance liquid chromatography with tandem mass spectrometric detection (LC-MS/MS).
abstract: 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 C18 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.
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Jiang
authors.forename: Xiao
authors.initials: X
authors.lastname: Huang
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.forename: Dan
authors.initials: D
authors.lastname: Zhu
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.forename: Jiaying
authors.initials: J
authors.lastname: Wang
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D057230:Limit of Detection; D011684:Purine Nucleosides / Q000097:blood; D011786:Quality Control; D051381:Rats; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C529213:2-amino-9-(2,3-dideoxy-2,3-dihydroarabinofuranosyl)-6-methoxy-9H-purine; D011684:Purine Nucleosides