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Rapid and sensitive HPLC‐MS/MS method for pharmacokinetic assessment of ribavirin in healthy Chinese
Author(s) -
Zhou ZhiLing,
Yu XiYong,
Yang Min,
Peng HuaiYan,
Chen TieFeng,
Lin QiuXiong,
Shan ZhiXin,
Liu XiaoYing,
Deng ChunYu,
Zhu Ping,
Huang XiaoZhong,
Lin ShuGuang
Publication year - 2008
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.1074
Subject(s) - ribavirin , chemistry , pharmacokinetics , chromatography , formic acid , high performance liquid chromatography , pharmacology , medicine , biochemistry , genotype , gene
Abstract A rapid and sensitive quantitative assay method was developed for determining ribavirin pharmacokinetic in human plasma. The chromatographic separation was achieved within 4.5 min using a SinoChrom ODS‐BP column (4.6 × 150 mm, 5 µm) with acetonitrile–water (1 mmol/L ammonium acetate buffer, 0.1% formic acid; 15:85, v/v) at a constant flow rate of 0.8 mL/min. The MRM pairs were m/z 245.2 → m/z 113.1 for ribavirin and m/z 226.1 → m/z 152.1 for acyclovir (internal standard), respectively, with dwell times of 200 ms for each transition. The results showed calibration curve for ribavirin was linear over a concentration range of 1–1000 ng/mL. The lower limit of quantification (LLOQ) was 1 ng/mL ribavirin. Twenty healthy volunteers received a 300 mg oral dose of ribavirin. Blood samples were then collected up to 120 h postdosing. All plasma data were comodeled for ribavirin by using noncompartmental modeling. The single dose of ribavirin was well tolerated and no serious adverse effects occurred. The mean time to maximum concentration was about 1.25 h. The mean maximum concentration of drug in plasma for oral ribavirin was 250 ng/mL. The mean elimination half‐life was 43.6 h. The present study describes a simple, specific, sensitive HPLC–MS/MS method for measuring plasma drug concentration and analyzing human pharmacokinetics of ribavirin. Copyright © 2008 John Wiley & Sons, Ltd.