大鼠血浆佐米曲普坦的HPLC测定方法学研究

 目的建立大鼠血浆中佐米曲普坦的高效液相测定方法,并研究大鼠不同途径给药后的药动学。方法采用甲基叔丁基醚为溶剂,提取药物。以0.05%三乙胺(用磷酸调至pH 2.70)-乙腈(92∶8)为流动相,色谱柱为Dikma Diamonsil C₁₈柱(4.6 mm×200 mm,5μm),流速1.2 mL·min_-1,荧光检测的激发波长225 nm,发射波长360 nm。结果佐米曲普坦在2.5～1 000μg·L^-1内线性关系良好(r=0.999 7)。高、中、低3种浓度的提取回收率分别为90.10%,91.75%,86.79%,方法回收率分别为103.55%,94.49%,98.79%,日内和日间RSD均小于4%,最低检测限为1μg·L^-1。计算出灌胃、静注、鼻腔给药途径主要药动学参数分别为:t_1/2(2.03±0.88)h,ρ_max(144±28)μg·L^-1,t_max(0.85±0.14)h,AUC_0～t(442±110)μg·h·L^-1;t_1/2(1.40±0.12)h,ρ_max(567±55)μg·L^-1,AUC_0～t(1 075±128)μg·h·L^-1;t_1/2(1.48±0.23)h,ρ_max(304±34)μg·L^-1,t_max(0.65±0.14)h,AUC_0～t(685±43)μg·h·L^-1。结论该方法操作简单、快速、准确、重现性好,适用于大鼠血浆中佐米曲普坦浓度的检测及其药动学研究。

Study on Determination of Zolmitriptan in Rat Plasma by HPLC

OBJECTIVE To develop a HPLC method for the determination of zolmitriptan in rat plasma and study its pharmacokinetics after different administration.METHODS Plasma samples were extracted with methyl tertiarybutyl ether.HPLC separation was carried out on a Dikma Diamonsil C₁₈ column with the mobile phase consisting of 0.05% triethylamine in water(adjusting to pH 2.70 with 85% phosphoric acid) and acetonitrile(92∶8),pumped at flow rate of 1.2 mL·min^-1.Fluorescence detection was performed at 225 nm(excitation) and 360 nm(emission).RESULTS The calibration curve was linear in the concentration range of 2.5～1 000 μg·L^-1(r=0.999 7).The extraction recoveries of low,medium and high concentrations were 90.10%,91.75%,86.79%,respectively,and the relative recoveries were 103.55%,94.49%,98.79%,respectively.The RSDs of intra-day and interday were both less than 4%.The detection limit was 1 μg·L^-1.The pharmacokinetic parameters of zolmitriptan in rats were obtained after three route administration.The main pharmacokinetic parameters after intragastric,intravenous and intranasal administration were as follows: t_1/2(2.03±0.88),(1.40±0.12) and(1.48±0.23)h;ρ_max(144±28),(567±55) and(304±34) μg·L^-1;t_max(0.85±0.14),(0.65±0.14)h;AUC_0→t(442±110),(685±43) and(1 075±128) g·h·L^-1, respectively.CONCLUSION The method was sensitive,simple and repeatable.It was suitable for pharmacokinetic study of zolmitriptan in rats after different route administration.