RP-HPLC测定盐酸青藤碱不同给药途径的血药浓度及药动学研究

 目的　采用RP HPLC测定盐酸青藤碱灌胃和皮肤给药后不同时间大鼠体内血清浓度 ,计算出灌胃和皮肤给药途径主要药动学参数。方法　采用RP HPLC以乙腈0.01mol·L^-1磷酸二氢钠溶液-四甲基二乙胺 (46∶54∶0.22)为流动相,磷酸调至pH6.9,C₁₈ODS柱(4.6mm×25.0mm,5μm),紫外检测波长为26.3nm。 结果　盐酸青藤碱在 0.25～10.0μg·mL^-1范围内呈良好线性关系(r=0.9995),方法的平均回收率达98.5%,RSD=13%。计算出灌胃给药途径主要药动学参数:Ke0.31h-1,AUC18.07μg·h·mL^-1,t_{1/22.24h,cmax6.26μg·mL^-1,tmax0.75h ;皮肤给药途径主要药动学参数:Ke0.92h^-1,AUC32.4μg·h·mL^-1,t1/2 0.75h,cmax1.17μg·mL-1,tmax1h。结论　本法分离效果好 ,分析速度快 ,方法稳定 ,结果准确。}

Determination of sinomenine HCl in serum by HPLC and its pharmacokinetics after different administration

OBJECTIVE A RP-HPLC assay was developed to determine the concentration of sinomenine HCl in serum and its pharmacokinetics was studied in rats after ig and skin administration.METHODS C₁₈H₃₇ column was eluted with the mobile phase of acetonitrile-0.01 mol·L^-1 sodium phosphate monobasic-N,N,N′,N′-tetramethlenediamine(46:54:0.22.pH 6.9)and the ultraviolet wavelength was at 263 nm.RESULTS The assay was linear within the range of 0.25～10.0μg·mL^-1,(r=0.999 5).The mean recovery was 98.5% with RSD 1.3%.The pharmacokinetic parameters of sinomenine HCl in rats were obtained after two administration.The pharmacokinetic parameters after an intragastric administration included:Ke was 0.31,AUC was 18.07μg·h·mL ^-1,t_1/2 was 2.24h,c_max was 6.26μg·mL^-1,t_max was 0.75h.The pharmacokinetic parameters after a subcutanous administration included:Ke was 0.92,AUC was3.24μg·h·mL^-1,t_1/2 was 0.75h,c_max was 1.17μg·mL^-1,t_max was 1 h.CONCLUSION This method was easy, rapid,accurate and sensitive.