液相色谱-质谱联用法测定罗库溴铵血药浓度

Quantitative determination of Rocuronium bromide in human plasma by a liquid chromatography-tandem mass spectrum method

目的建立液相色谱-质谱联用（liquid chromatography-tandem mass spectrum,LC-MS）方法测定血浆中罗库溴铵浓度,并对静脉注射0.9 mg/kg该药物的患者2 h内的血药浓度进行测定。方法血浆中加入内标盐酸维拉帕米后用乙腈沉淀蛋白法进行处理,离心后取上清进样。选用Atlantis T3（4.6 mm×150 mm,5μm）色谱柱分离,流动相为乙腈-甲酸铵（60∶40,5 mmol/L,pH=5.5）,流速1 mL/min,柱后三通分流,0.2 mL/min流量进入质谱。质谱采用电喷雾（electrospray ionization,ESI）接口,选用正离子模式,检测方式为选择性离子监测（selected ion monitor,SIM）模式。结果罗库溴铵在0.1~10μg/mL范围内呈良好的线性关系,精密度及稳定性均符合生物样本测定要求。结论 LC-MS是一种简单、快速、准确测定罗库溴铵血药浓度的方法,并成功应用于静注2 h内临床样本的测定。

Objective To establish a liquid chromatography-tandem mass spectrum（LC-MS）method to determine the concentration of Rocuronium bromide in plasma.The method was applied to the plasma of patients who use the drug via intravenous injection within 2 hours. Methods After addition of Verapamil Hydrochloride as internal standard（IS）,plasma samples were precipitated by acetonitrile.After centrifuging,the supernate was taken to analysis.The separation was carried out on an Atlantis T3（4.6 mm×150 mm,5μm）column,and the mobile phase was acetonitrile-ammonium formate（60∶40,5 mmol/L,pH=5.5）at a rate of 1 mL/min with a three-way valve after the column to separate the flow and control the flow which runs in the mass spectrum at a rate of 0.2 mL/min.An electrospray ionization（ESI）was adopted as the interface.The samples were detected in positive mode with selected ion monitor（SIM）. Results A good linearity was obtained in the range of 0.1~10μg/mL,and the accuracy,stability and other parameters of the method meet the detecting require for biological samples. Conclusions LC-MS method is a simple,rapid and accurate method that can be applied to measuring the concentration of Rocuronium bromide in plasma,and it′s also succeed in measuring the clinical samples within 2 hours.