HPLC-荧光法测定氨磺必利血药浓度及其药动学研究

目的: 建立测定人体血浆中氨磺必利高效液相色谱法,测定健康志愿者口服氨磺必利片48 h内血药浓度,进行药动学研究。 方法: 采用10%三氯醋酸直接沉淀提取血浆,固定相为C₁₈,以庚烷磺酸钠醋酸溶液(pH 4.85)-乙腈(80: 20)为流动相,荧光检测波长为λ_ex=280 nm,λ_em=370 nm。 结果: 氨磺必利线性范围为5~800 ng·mL^-1(r=0.9997),低、中、高3个浓度平均方法回收率分别为105.1%、105.4%、101.3%,日内、日间精密度RSD均<4%;AUC_0~∞为(3545.74±1199.58)ng·h·mL^-1,AUC_0~t为(3348.50±1161.27)ng·h·mL^-1,C_max为(457.69±232.62)ng·mL^-1,T_max为(4.15±1.31)h,t_1/2为(10.77±5.77)h。 结论: 本法简便、快速、经济、准确,可用于测定人血浆中氨磺必利的浓度及药动学研究。

Objective: To establish an HPLC method for the determination of amisulpride levels in human plasma,determine the amisulpride plasma concentration in healthy volunteers within 48 hours after oral administration of amisulpride tablets,and study on pharmacokinetics. Methods: The amisulpride was extracted from plasma by 10% trichloroacetic acid.Chromatographic separation has been achieved on C₁₈ column with sodium heptanesulfonate-acetic acid(pH 4.85)and methyl cyanides(80: 20)as the mobile phase.The fluorescence detection was used to determine amisulpride at λ_ex =280 nm and λ_em =370 nm. Results: The linear range was 5-800 ng·mL^-1(r=0.9997).The average method recovery of low,middle and high concentration was 105.1%,105.4%,and 101.3%,respectively.RSDs of inter- and intra-day precision were both less than 4%.AUC_0-∞ was(3545.74±1199.58)ng·h·mL^-1,AUC_0-t was(3348.50±1161.27)ng·h·mL^-1,C_max was(457.69±232.62)ng·mL^-1,T_max was(4.15±1.31)h,t_1/2 was(10.77±5.77)h. Conclusion: The method is simple,rapid,economical and accurate for determination of amisulpride in human plasma and pharmacokinetic study.