液相色谱-串联质谱法测定人血浆中盐酸度洛西汀的浓度及其药代动力学研究  

Determination concentration of duloxetine hydrochloride in human plasma by HPLC-MS/MS and study on its pharmacokinetics

作　　者：赵瑞柯[1] 刘家稳[1] 程钢[1] 唐靖[1] 宋娟[1] 彭文兴[1] 

机构地区：[1]中南大学湘雅二医院临床药学教研室,长沙410011

出　　处：《中国临床药理学杂志》2010年第2期137-140,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的建立高效液相色谱-串联质谱联法测定人血浆中度洛西汀(抗抑郁药)并研究其在健康人体的药代动力学。方法5名男性与5名女性健康志愿者口服盐酸度洛西汀肠溶片60mg,色谱柱为phenomenex C18,流动相为水相(5mmol.L-1醋酸胺,含0.02%的甲酸)-乙腈=55∶45;电喷雾电离源正离子模式(ESI+),以氟西汀为内标。用高效液相色谱-串联质谱法测定盐酸度洛西汀血药浓度,并计算药代动力学参数。结果度洛西汀血浆浓度在0.89～106.80ng·mL-1内与峰面积积分值线性关系良好(γ=0.9977)。方法回收率在93.19%～107.27%,萃取回收率在72.81%～89.96%。日内、日间标准偏差均小于11%。主要药代动力学参数:Cmax为(44.40±17.78)ng·mL-1,tmax为(6.10±1.29)h,t1/2为(12.81±2.31)h;AUC0-60和AUC0-∞分别为(696.04±337.82),(733.82±343.40)ng.h.mL-1。结论本方法操作简单,结果准确可靠,适于度洛西汀的血药浓度监测和药代动力学研究。Objective To establish a liquid chromatography- tandem mass spectrometry （LC- MS/MS） method for the determination concentration of duloxetine in human plasma and study on its pharmaeokinetics in healthy human. Methods The separation of duloxetine was performed on Phenomenex C lscolumn with fluoxetine as the internal standard. The mobile phase was composed of 5 mmol·L^1 ammonium acetate with 0. 02% formic acid aeetonitrile （55： 45）. Electrospray ionization source was applied and operated in positive ion mode. A single dose of 60 mg duloxetine hydrochloride was given to 5 male and 5 female healthy volunteers and the plasma was separated. The concentration of duloxetine was determined by HPLC -MS/MS and the pharmacokinetic parameters were calculated. Results The linear range of duloxetine was 0.89 - 106. 80 ng· mL^-1 （γ = 0. 9977）. The methodological recovery and the extraction recovery ranged between 93.19% - 107.27% and 72. 81% -89.96% , respectively. Both the inter- day RSD and intra -day RSD were less than I 1%. The main pharmacokinetic parameters after a single dose of 60rag duloxetine are as follows： Cmax was （44.40 ± 17.78） ng· mL^-1, t was （6.10±1.29） h, t1/2was （12.81 ±2.31） h;AUC0 60and AUC0-∞ were （696.04 ±337.82）, （733.82 ±343.40） ng·h·mL^-1,respectively. Conclusion The method is simple, accurate and reliable, and suitable for the determination of duloxetine in therapeutic drug monitor and its pharmacokinetics study.

关 键 词：度洛西汀 液相色谱-串联质谱 血药浓度 

分 类 号：R969.1[医药卫生—药理学] R971.43[医药卫生—药学]