LC-MS/MS法测定人血浆中舒芬太尼的血药浓度

Determination of sufentanil in human plasma by LC-MS/MS

目的建立液质联用（LC—MS／MS）法测定血浆中舒芬太尼血药浓度。方法以芬太尼为内标，血浆样品经乙腈沉淀蛋白后，以Ultimate XB C18（100mm×2．1mm，3．0μm）柱为色谱柱，流动相为水-甲醇（15：85，V／V），各含10mmol·L^-1乙酸铵，流速为0．2mL·min^-1，柱温加℃；质谱条件为电喷雾电离源（ESI），检测方式为正离子电离、多离子反应监测（MIIM），用于定量分析的离子为舒芬太尼m／z387．2→238．1，芬太尼m／z337．2→188．2。结果舒芬太尼线性范围为0．05～2μg·L^-1（r=0．9964），线性关系良好。舒芬太尼的提取回收率为83．68％。88．06％。批内和批间精密度RSD均〈10％。结论本研究建立的测定舒芬太尼血药浓度的方法简单、快速、准确、灵敏，可用于临床上血药浓度监测和药动学研究。

AIM To develop a LC-MS/MS assay to determine sufentanil in human plasma. METHODS Fentanyl was used as an interal standard. Plasma samples were precipitated by acetonitril. The separation was carried out on an Ultimate XB C18（ 100 mm × 2.1 mm, 3.0 μm） column at 40℃. The mobile phase consisted of water-methanol solu- tion （ 15 ： 85, V/V） with 10 mmol·L^-1 ammonium acetate at a flow-rate of 0.2 mL·min^-1. Electrospray ionization（ESI） source was applied and operated in the positive ion mode. Quantitaion was performed using multiple reaction monitoring （MRM） of the m/z 387.2→238.1 for sufentanil, and m/z 337.2→188.2 for fentanyl. RESULTS The liner calibration curves were obtained in the range of 0.05 - 2μg·L^-1 for sufentanil. The extraction recovery for sufentanil was ranged from 83.68 % - 88.06%. The relative standard deviation of the intra-assay and inter-assay precision of variation was less than 10%. CONCLUSION It is an accurate, sensitive and rapid method that can be applied to the evaluation of sufentanil target, and suitable for clinical pharmacokinetic study of sufentanil.