HPLC法测定盐酸氟桂利嗪分散片的血药浓度及药动学研究

Determination of plasma flunarizine hydrochloride dispersible tablets by HPLC

目的:建立盐酸氟桂利嗪分散片体内血药浓度的HPLC测定方法,研究其药动学.方法:色谱柱为DiamodTM C18柱(150 mm×4.6 mm,5 μm);流动相为0.01 mol·L-1磷酸二氢铵缓冲液-甲醇(35:65),用磷酸调节pH至3.50.流速为1.0 mL·min-1,柱温为室温.荧光检测激发波长为254 nm,发射波长为308 nm.内标为对羟基苯甲酸丙酯.10例健康受试者服用盐酸氟桂利嗪分散片20 mg,采用HPLC法测定盐酸氟桂利嗪的血药浓度.结果:盐酸氟桂利嗪在1.5～100 ng·mL-1浓度内,其与内标的峰面积的比值与浓度呈良好的线性关系(r=0.999 8),低、中、高浓度的血浆标准样品的相对回收率在99.10%～101.88%,日内、日间RSD在1.99%～4.44%.盐酸氟桂利嗪分散片AUC0-t为(424.27±74.01)ng·h·mL-1,Cmax为(67.02±14.89)ng·mL-1,Tmax为(2.90±0.42)h,t1/2Ke为(9.73±3.15)h.结论:本试验提供了盐酸氟桂利嗪分散片体内血药浓度的HPLC测定方法及药动学参数,为临床应用提供了依据.

Objective： To determine the plasma concentration and pharmacokinetic parameters of flunarizine hydrochloride dispersible tablets by HPLC. Methods： 10 healthy volunteers were administered with a single dose of flunarizine hydrochloride dispersible tablets （20 mg）. Plasma concentrations of flunarizine hydrochloride were measured by HPLC. The HPLC conditions were as follows： Diamod^TM C18 column （150 mm×4.6 mm, 5μm）, an eluant consisted of 0.01 mol·L^-1 ammonium dihydrogen phosphate buffermethanol （35：65, pH = 3.5 adjusted with phosphoric acid） with a flow rate of 1.0 mL·min^-1, and fluorescence detection at Ex = 254 nm and Em = 308 nm. Propyl p-hydroxy benzoate was used as an internal standard. Results：The linear plot of concentration versus of peak area of internal standard was found in the range of 1.5 - 100 ng·mL^-1（ r =0.999 8）. The mean recovery rate of three batches of plasma sample concentrations was within 99.10% - 101.88% with within-day and among-day RSD of 1.99% -4.44%. The pharmacokinetic parameters after administration of flunarizine hydrochloride dispersible tablets （20mg） were shown as AUC0-t（424.276±74.01） ng·h·mL^-1 ; Cmax（67.02 ± 14.89） ng·mL^-1 ; Tmax（2.90±0.42）h, and t1/2 Ke （9.73 ± 3.15 ）h. Conclusion： The methodology to determine plasma concentration and pharmacokinetic profiles of flunarizine hydrochloride dispersible tablets by HPLC were achieved.