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目的:建立LC-MS/MS法,测定大鼠血浆中利巴韦林及其毒代动力学参数。方法:LC条件:Waters Atlan-tis T3色谱柱(4.6 mm×150 mm,3μm),柱温为40℃,流动相为0.1%甲酸水溶液-0.1%甲酸乙腈溶液(95∶5),流速为1 000μL.min-1,进样量为2μL;MS条件:电喷雾离子源,正离子电离模式,多反应离子监测的MS扫描方式。以10、40、160 mg.kg-1.d-1剂量每日1次、连续28 d给大鼠灌胃使用利巴韦林药液,测定其血药浓度和毒代动力学参数。结果:利巴韦林血药浓度线性范围为5～5 000μg.L-1,最低定量限为5μg.L-1;日内和日间精密度良好,RSD均小于15%,准确度均在±15%以内。所测利巴韦林毒代动力学参数基本上与给药剂量成正相关,未见有明显药物蓄积现象,与毒性表现基本一致。结论:该法专属性强、灵敏度高、操作简便,适用于生物样本中利巴韦林的测定及毒代动力学研究。
Objective: To establish a LC-MS / MS method for the determination of ribavirin in plasma and its toxicokinetic parameters. Methods: LC conditions: Waters Atlan-tis T3 column (4.6 mm × 150 mm, 3 μm) with a column temperature of 40 ℃ and a mobile phase of 0.1% formic acid in water and 0.1% formic acid in acetonitrile 000μL.min-1, injection volume 2μL; MS conditions: electrospray ionization source, positive ionization mode, multi-reactive ion monitoring MS scanning mode. The rats were orally administrated with ribavirin at 10, 40, 160 mg.kg-1.d-1 once daily for 28 days. The plasma concentrations and toxicokinetic parameters were determined. Results: The linear range of ribavirin plasma concentration was 5 ~ 5000μg.L-1, the lowest limit of quantification was 5μg.L-1; the intra-day and inter-day precision was good, RSD was less than 15% and the accuracy was within ± Within 15%. The measured pharmacokinetic parameters of ribavirin are basically proportional to the dose administered, no significant drug accumulation phenomenon, basically consistent with the toxicity. Conclusion: The method is highly specific, sensitive and easy to operate. It is suitable for the determination of ribavirin in biological samples and its toxicokinetic study.