LC-MS/MS同时测定人血浆中阿莫西林-氨溴索浓度及其药动学研究

 目的建立LC-MS/MS同时测定人血浆中阿莫西林/氨溴索浓度。方法以Lichrospher C₁₈(4.6mm×150mm,5μm)为色谱柱,流动相为甲醇溶液(含0.2%甲酸)和水溶液(含0.2%甲酸),采用梯度洗脱进行分析,流速为1.0mL·min^-1,柱温为30℃。血浆样品经甲醇沉淀后进样,采用多反应监测(MRM)方式对样品进行测定。结果血浆中阿莫西林线性范围为5～20000μg·L^-1,氨溴索线性范围为1～200μg·L^-1;批间和批内精密度RSD均小于9%;方法的准确度为(100±7)%;最低定量限浓度(LLOQ)阿莫西林为5μg·L^-1,氨溴索为1μg·L^-1。结论本试验建立了同时测定阿莫西林和氨溴索浓度的方法,该方法灵敏、准确、简便、快速,适用于阿莫西林/氨溴索人体药动学研究。

Simultaneous Determination of Amoxicillin/Ambroxol in Human Plasma by LC-MS/MS and Pharmacokinetic Study

OBJECTIVE To develop a LC-MS/MS method for simultaneous determination of amoxicillin and ambroxol in human plasma. METHODS The Lichrospher C₁₈ column (4.6 mm×150 mm, 5 μm) was used. The mobile phase consisted of methanol (containing 0.2% formic acid) and 0.2% formic acid water using the gradient program pumped at a flow rate of 1.0 mL·min^-1 at 30 ℃. Plasma samples were loaded after methanol precipitation and analyzed with MRM method. RESULTS Calibration curves were linear in the concentration range of 5–20 000 μg·L^-1 for amoxicillin and 1–200 μg·L^-1 for ambroxol. Both of the intraand interrun precisions were less than 9% and the accuracy was (100±7)%. The LLOQs of amoxicillin and ambroxol were determined as 5.0 and 1.0 μg·L^-1, respectively. CONCLUSION The established method was sensitive, accurate, simple and rapid for simultaneous determination of the concentrations of amoxicillin and ambroxol, which was applicable to the clinical monitoring and pharmacokinetic studies.