摘要
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pH2．70）．乙腈（92：8）为流动相，色谱柱为Dikma Diamonsil C18柱（4．6mm×200mm，5μm），流速1．2mL·min^-1，荧光检测的激发波长225nln，发射波长360nln。结果佐米曲普坦在2．5～1000μg·L^-1内线性关系良好（r=0．9997）。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：t1／2（2．03±0．88）h，ρmax（144±28）μg·L^-1，tmax（0．85±0．14）h，AUC0～t（442±110）μg·h·L^-1；t1／2（1．40±0．12）h，ρmax（567±55）μg·L^-1，AUC0～t（1075±128）μg·h·L^-1；t1／2（1．48±0．23）h，ρmax（304±34）μg·L^-1，tmax（0．65±0．14）h，AUC0～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。
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 CIS 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（excitafion） and 360 nm（emission）. RESULTS The calibration curve was linear in the concentration range of 2.5～1000μg·L^-1 （ r = 0.9997）. The extraction recoveries of low, medium and high concentratious 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 inter-day were both less than 4%. The detection limit was 1μg·L^-1. The pharmacokinetic parameters of zolmitriptan in rats were obtained after three mute administration. The main pharmacokinetic parameters after intragastric, intravenous and intranasal administration were as follows： t1/2（2.03 ±0.88）, （ 1.40 ± 0.12） and（ 1.48 ± 0.23）h; ρmax（ 144 ± 28）,（567±55） and （304±34）μg·L^-1;tmax（0.85±0.14）,（0.65±0.14）h;AUC0→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.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2006年第15期1171-1174,共4页
Chinese Pharmaceutical Journal
基金
国家自然科学基金资助项目(30171112)
