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目的:建立大鼠血浆中吴茱萸碱和吴茱萸次碱的SPE-HPLC测定方法,并用于透皮给药后的药动学研究。方法:Kromasil C18(4.6 mm×250 mm,5μm),以乙腈-水-四氢呋喃-冰醋酸(51∶48∶1∶0.1)为流动相,流速1 mL.min-1,检测波长为225 nm,柱温35℃,以氯氟舒松为内标溶液,固相萃取后采用HPLC法测定吴茱萸碱和吴茱萸次碱的血浆浓度。结果:透皮给药后,药-时曲线符合一室模型,吴茱萸碱主要药动学参数Ka0.224 h-1,Ke0.114 h-1,Cmax0.211 mg.L-1,Tpeak6.132h,吴茱萸次碱主要药动学参数Ka0.220 h-1,Ke0.118 h-1,Cmax0.272 mg.L-1,Tpeak6.102 h。结论:本方法简便、准确、灵敏度高,适用于大鼠透皮给药后吴茱萸碱和吴茱萸次碱的血药浓度测定及其药动学研究。
OBJECTIVE: To establish a method for the determination of evodiamine and rutaecarpine in rat plasma by SPE-HPLC and to study the pharmacokinetics after transdermal administration. METHODS: Kromasil C18 (4.6 mm × 250 mm, 5 μm) was used as the mobile phase at a flow rate of 1 mL · min-1 with acetonitrile-water-tetrahydrofuran-glacial acetic acid (51:48:1:0.1) The column temperature was 35 ℃, and chlorfluazuron was used as the internal standard solution. The plasma concentration of evodiamine and rutaecarpine was determined by HPLC after solid phase extraction. Results: After transdermal administration, the drug-time curve accorded with one-compartment model. The main pharmacokinetic parameters of evodiamine were Ka0.224 h-1, Ke0.114 h-1, Cmax0.211 mg.L-1, Tpeak6.132h , The main pharmacokinetic parameters of rutaecarpine Ka0.220 h-1, Ke0.118 h-1, Cmax0.272 mg.L-1, Tpeak6.102 h. Conclusion: The method is simple, accurate and sensitive. It is suitable for the determination of evodiamine and rutaecarpine in rats after transdermal administration and its pharmacokinetic study.