HPLC-MS法测定右酮洛芬人体血药浓度及经尿排泄特征

目的:建立高效液相色谱-质谱联用测定右酮洛芬人体血(尿)药浓度的方法,考察右酮洛芬的血药浓度及经尿排泄特征.方法:色谱柱为Inspire-C18(150 mm×2.1 mm,5 μm),以甲醇-水(5 mmol·L-1醋酸铵和0.05%乙酸)(68∶32,v/v)为流动相.质谱采用电喷雾离子源四级杆质谱,以选择性离子监测方式进行负离子检测.12名健康受试者单次静脉滴注右酮洛芬氨丁三醇注射液25mg后,采集血浆并定时收集尿液.采用甲醇直接沉淀法处理样品后,评价右酮洛芬的血药浓度及尿排泄特征.结果:右酮洛芬在0.01~20.66 μg·ml-1浓度范围内线性关系良好,精密度(RSD)为4.3%～7.2%,准确度(RE)为0.7%～5.3%,绝对回收率为98.9%～102.2%.静滴右酮洛芬氨丁三醇注射液25mg后,Cmax(3.53±0.57)μg·ml-1,AUC0-t(7.98±0.90)μg·h·ml-1,t1/2(2.0±0.6)h,tmax(0.5±0.03)h.24 h内累积排泄率为(1.2±0.23)%.结论:该方法简单,符合生物样品分析要求;右酮洛芬氨丁三醇在体内以右酮洛芬形式经尿排泄较少,12 h内基本排泄完全.

Determination of Dexketoprofen in Human Plasma by HPLC-MS and Evaluation of Urinary Excretion

Objective:To establish an HPLC-MS method for the determination of dexketoprofen in plasma and investigate the urinary excretion profile.Method:An Inspire-C₁₈（150 mm×2.1 mm,5μm）column was used and methanol-5 mmol · L^-1ammonium acetate containing 0.05%acetic acid（68:32,v/v）was the mobile phase with electrospray ionization source and negative ion mode. Totally 12 healthy volunteers were injected dexketoprofen trometamol injections with a single dose of 25 mg.Then the plasma and urine samples from the subjects were collected at different time points and precipitated directly with methanol to evaluate the concentration in plasma and the urinary excretion profile of dexketoprofen.Result:The calibration curve was linear within the range of 0.01～20.66μg · mL^-1for dexketoprofen in plasma and urine with RSD of 4.3%～7.2%,RE of 0.7%～5.3%and the average recovery of 98.9%～102.2%.The pharmacokinetic parameters.of dexketoprofen trometamol with a single dose of 25 mg were as follows:C_maxof（3.53±0.57）μg ·mL^-1,AUC_0-1of（7.98±0.90）μg · h · mL^-1,t_1/2of（2.0±0.6）h and t_maxof（0.5±0.03）h.Cumulative excretion rate of dexketoprofen was（1.2±0.23）%within 24 h.Conclusion:The HPLC-MS method meets the requirement of biological sample analysis.Dexketoprofen trometamol is almost completely excreted in the form of dexketoprofen in urine within 12 h after intravenous drip in healthy volunteers.