人血浆中氢吗啡酮的LC-MS测定方法及其应用

目的:建立人血浆中氢吗啡酮的LC-MS测定法,并研究术后镇痛患者恒速静脉泵注盐酸氢吗啡酮后氢吗啡酮的药代动力学特征。方法:血浆样品经碱化乙酸乙酯提取后,进行LC-MS分析,流动相为甲醇-5 mmol·L-1醋酸铵水溶液(含1%甲酸)(12∶88,v/v)。氢吗啡酮检测离子为M+H]+m/z 286.2,内标(纳洛酮)检测离子为M+H]+m/z 328.2。测定手术后镇痛患者恒速静脉泵注盐酸氢吗啡酮注射液1.5 mg后血浆中氢吗啡酮的浓度,并计算主要药动学参数。结果:在0.06～60 ng·mL-1范围内,线性关系良好;批内批间精密度RSD均小于10%;提取回收率为68.8%～75.7%。结论:本方法可用于氢吗啡酮人体药动学研究。

Determination of Hydromorphone in Human Plasma by a Sensitive RP-HPLC-ESI-MS Method and Its Application

Objective: To establish an LC-MS method for the determination of hydromorphone in human plasma and apply it to a clinical pharmacokinetic study.Methods: Plasma samples,alkalized with saturated sodium bicarbonate(1∶1,v/v) were extracted with ethyl acetate and then analyzed by LC-MS.Chromatographic separation was performed with a mobile phase of 5 mmol·L-1 ammonium acetate buffer containing 1% formic acid-methanol(88∶12,v/v).Hydromorphone and the internal standard(IS) were ionized with electrospray ionization-mass spectrometry in positive ion mode,and then detected by selected ion monitoring using the protonated molecules at m/z 286.2 for hydromorphone and m/z 328.2 for the IS.The method was applied in a pharmacokinetic study,and the plasma concentrations of hydromorphone in Chinese patients following surgery were determined after intravenous infusion of 1.5 mg hydromorphone hydrochloride injection.Results: The calibration curves were linear over the range of 0.06～60 ng·mL-1.The average recoveries of hydromorphone in plasma were 68.8% to 75.7%.The RSD of intra-and inter-day precision and accuracy for hydromorphone were 10% or less.Conclusion: The developed method can be applied to the pharmacokinetic study and therapeutic drug monitoring of hydromorphone.