UHPLC-MS/MS同时检测人血浆中5种麻醉药物

Simultaneous Determination of 5 Anesthetics in Human Plasma by UHPLC-MS/MS

目的建立UHPLC-MS/MS同时检测人血浆中瑞芬太尼、舒芬太尼、依托咪酯、右美托咪定、地佐辛5种麻醉药物的分析方法,为指导临床用药提供参考。方法血浆样品经乙腈沉淀蛋白质后进样分析,以普鲁卡因为内标,采用Agilent Poroshell 120 EC-C_(18)(2.1 mm×150 mm,2.7μm)色谱柱进行色谱分离;以甲醇-10 mmol·L^(-1)甲酸铵溶液(28∶72,用甲酸调节pH至3.5)为流动相,流速0.2 mL·min^(-1);采用电喷雾电离源正离子检测模式,以多反应监测方式进行分析。结果人血浆中瑞芬太尼、舒芬太尼、依托咪酯、右美托咪定、地佐辛分别在0.25~25.32(r=0.9987),0.27~27.48(r=0.9992),1.54~154.05(r=0.9995),0.51~51.35(r=0.9992),0.56~56.19(r=0.9988)ng·mL^(-1)内线性关系良好。日内和日间精密度RSD均<10.0%,提取回收率均处于92.8%~107.3%之间。该方法成功应用于30例临床患者血浆样本分析。结论该方法操作简单快速、灵敏度高、专属性高且稳定,适用于人血浆中瑞芬太尼、舒芬太尼、依托咪酯、右美托咪定、地佐辛5种麻醉药物的分析,能够服务于临床治疗药物监测。

OBJECTIVE To establish UHPLC-MS/MS method for simultaneous determination of the concentrations of remifentanil,sufentanil,etomidate,dexmedetomidine,dezocine in human plasma to provide reference for clinical drug use.METHODS The plasma samples were precipitated by acetonitrile,procaine was used as internal standard,and separated on Agilent Poroshell 120 EC-C^(18)(2.1 mm×150 mm,2.7μm)with the mobile phase of methanol and 10 mmol·L^(-1)ammonium formate solution(pH was adjusted to 3.5 with formic acid)(28∶72)at a flow rate of 0.2 mL·min^(-1).Multiple reaction monitoring was conducted in ion detection mode using positive electrospray ionization source.RESULTS The linear calibration curves of remifentanil,sufentanil,etomidate,dexmedetomidine and dezocine were obtained in the concentration range of 0.25−25.32(r=0.9987),0.27−27.48(r=0.9992),1.54−154.05(r=0.9995),0.51−51.35(r=0.9992),0.56−56.19(r=0.9988)ng·mL^(-1),respectively.The intra-and inter-day precision RSD was<10.0%and the absolute recovery was between 92.8%and 107.3%.This method was successfully applied to analyze the drugs in human plasma from thirty clinical samples.CONCLUSION The method is rapid,accurate,sensitive and reliable for determination of the concentrations of remifentanil,sufentanil,etomidate,dexmedetomidine,dezocine in human plasma,and proves to be suitable for clinical therapeutic drug monitoring.