液相色谱质谱联用法测定静脉复合麻醉患者血浆中舒芬太尼的浓度

 目的 建立液相色谱质谱联用（LC-MS/MS）测定静脉复合麻醉患者血浆中舒芬太尼的药物浓度方法。方法 血浆样品经2 mol· L^-1 NaOH溶液20 μL碱化后用乙醚萃取，以芬太尼为内标，采用LC-MS/MS测定。色谱柱为Diamonsil C₁₈柱（4.6 mm×150 mm， 5 μm），以甲醇-5 mmol·L^-1醋酸铵-醋酸（74∶26∶0.5）为流动相，流速为0.5 mL·min^-1；质谱条件采用TIS离子源，检测方式为正离子电离，多离子反应监测（MRM），用于定量分析的离子反应分别为m/z 387.2→m/z 238.2（舒芬太尼）和m/z 337.4→m/z 188.2（芬太尼）。结果 舒芬太尼在0.01~1.00 μg·L^-1（r=0.998 1）内线性关系良好，高、中、低3浓度的提取回收率在64.2%以上，日内、日间精密度均小于11.6%。结论 本试验建立的舒芬太尼血药浓度的测定方法简单、快速、准确、灵敏，可用于临床上复合麻醉中小剂量应用舒芬太尼患者的血药浓度测定及临床药动学研究。

Determination of Sufentanil in Plasma of Patients Receiving Intravenous Combined Anesthesia by LC-MS/MS

OBJECTIVE To establish a LC-MS/MS method for the determination of sufentanil plasma concentration in patients receiving intravenous combined anesthesia.METHODS After adding 2 mol·L-1 NaOH as the basification reagent,sufentanil was extracted from plasma by ether.Then sufentanil was determined by LC-MS/MS using fentanyl as the internal standard.Separation was carried on a Diamonsil C18 column(4.6 mm×150 mm,5 μm) with a mobile phase of methanol-5mmol·L-1 ammonium acetate-acetic acid(74:26:0.5) at the flow rate of 0.5 mL·min-1.TIS source was applied and operated in positive ion mode.Quantitative determination was performed using multiple reaction monitoring(MRM) of m/z 387.2→m/z 238.2 for sufentanil,and m/z 337.4→m/z 188.2 for fentanyl.RESULTS The calibration curve was in good linearity over the range of 0.01-1.00 μg·L-1(r=0.998 1).The extraction recovery for sufentanil were more than 64.2%,while the intra-day and inter-day precision(RSD) were lower than 11.6%.CONCLUSION The method is shown to be simple,rapid,accurate and sensitive,which can be applied to the determination of sufentanil and the pharmacokinetics study of sufentanil in patients receiving intravenous combined anesthesia.