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

关键词:  瑞芬太尼  舒芬太尼  依托咪酯  右美托咪定  地佐辛  超高压高效液相色谱-串联质谱法  血药浓度

Key words:  remifentanil  sufentanil  etomidate  dexmedetomidine  dezocine  UHPLC-MS/MS  plasma concentration

摘要:

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-C₁₈（2.1 mm×150 mm，2.7 μm）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=0.998 7），0.27~27.48（r=0.999 2），1.54~154.05（r=0.999 5），0.51~51.35（r=0.999 2），0.56~56.19（r=0.998 8）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。

Abstract:

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-C₁₈(2.1 mm×150 mm, 2.7 μm) 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=0.998 7), 0.27-27.48(r=0.999 2), 1.54-154.05(r=0.999 5), 0.51-51.35(r=0.999 2), 0.56-56.19(r=0.998 8)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.