基于液-质联用法研究10-羟喜树碱在大鼠体内的药动学行为

Pharmacokinetic study of 10-hydroxycamptothecin in rats based on LC/MS-MS techniques

目的:建立测定大鼠血浆中10-羟喜树碱浓度的液相色谱-串联质谱(LC/MS-MS)分析方法,并用于10-羟喜树碱注射液经时血药浓度的验证评价。方法:血浆样品经乙酸乙酯(含0.2%冰醋酸)提取处理,以0.1%甲酸-乙腈与0.1%甲酸-水溶液为流动相,梯度洗脱。采用电喷雾离子源(ESI)在正离子条件下,通过多反应监测模式(MRM)进行检测。结果:10-羟喜树碱的血浆浓度在7.812 5～1 000 ng·mL^(-1)范围内线性关系良好,日内与日间精密度的RSD均小于5%,提取回收率为91.73%～106.22%。结论:该方法快速且操作简单,适用于10-羟喜树碱及其一些制剂给药后的基础和临床药动学分析评价。

OBJECTIVE To develop a high-performance liquid chromatography-tandem mass spectrometry(LC/MS-MS)method for determination of 10-hydroxycamptothecin in rat plasma and apply to the verification of its plasma concentration time profile.METHODS Plasma samples were extracted by ethyl acetate containing 0.2%glacial acetic acid with the mobile phase composed of acetonitrile(containing 0.1%formic acid)and aqueous solution(containing 0.1%formic acid)through gradient elution.The detection was performed by MRM mode via electrospray ionization(ESI)source operating in the positive ionization mode.RESULTS The calibration curve of 10-hydroxycamptothecin in rat plasma was linear over the concentration range of 7.8125~1000 ng·mL-1.Intra-day and inter-day precision values(RSD)were less than 5%and the extraction recovery was 91.73%~106.22%.CONCLUSION The developed method is rapid,simple and suitable for the analytical evaluation on basic and clinical pharmacokinetics of 10-hydroxycamptothecin and other preparations.