中南药学

目的建立HPLC-MS测定人血浆中克拉霉素的方法,并用于药物动力学研究。方法采用Thermo C18柱(150 mm×2.1 mm,5μm),柱温45℃,流动相为乙腈-15 mmol.L-1醋酸铵水溶液(含0.5%甲酸,0.1%三氟乙酸)(42∶58),流速0.35 mL.min-1;以罗红霉素为内标,采用电喷雾电离正源,选择性离子方式检测。克拉霉素及内标用于定量分析的离子分别为m/z748.6、m/z837.8。血浆样品用甲醇沉淀蛋白后进样。结果克拉霉素在12.1~3400.0 ng.mL-1线性关系良好,相关系数为0.999 9,最低检测限为2.0 ng.mL-1。萃取回收率>83.0%,方法回收率103.7%~106.7%,日内日间精密度均<7.9%。结论该方法结果准确、灵敏度高,适用于克拉霉素药物动力学和生物等效性研究。

Objective To establish an HPLC-MS method for the determination of clarithromycin in the human plasma and to study the pharmacokinetics of clarithromycin.Methods The analytes were determined by HPLC-MS method using Thermo C18 column(150 mm×2.1 mm,5 μm),acetonitrile-15 mmol·L-1 ammonium acetate solution with 0.5% formic acid and 0.1% trifluoroacetic acid(42∶58) as the mobile phase at 0.35 mL·min-1,with positive ion SIM detection of clarithromycin(m/z=748.6),using roxithromycin(m/z=837.8) the internal standard.The column temperature was 45℃.The plasma was deposited by methanol directly.Results The calibration curve was linear within 12.1～3 400.0 ng·mL-1(r =0.9999).The limit of quantitation was 2.0 ng·mL1.The extraction recovery was >83.0% and the method recovery was 103.7%～106.7%.The relative standard deviations for the intra-day and inter-day were <7.9%.Conclusion The method is simple,accurate,fast and sensitive and suitable for the pharmacokinetics and bioequivalence study of clarithromycin.