用HPLC研究α-倒捻子素大鼠灌胃给药的排泄

目的: 研究α-倒捻子素大鼠灌胃给药的排泄特征。方法: 采用大鼠灌胃给予α-倒捻子素的方式,在24 h内收集胆汁,48 h内收集尿液和粪便,建立并采用HPLC测定生物样品中α-倒捻子素含量。生物样品采用甲醇提取;HPLC采用C₁₈(250 mm×4.6 mm,5 μm)反相色谱柱,流动相为甲醇-水(95:5),流速为1.0 mL·min^-1,检测波长为317 nm。结果: HPLC-UV方法测定,胆汁中α-倒捻子素浓度在0.12~120 μg·mL^-1,尿液中α-倒捻子素浓度在0.16~160 μg·mL^-1,粪便中α-倒捻子素浓度在0.26~5200 μg·g^-1,其峰面积与质量呈线性相关,相关系数大于0.999。α-倒捻子素灌胃给药后主要以粪排泄为主,占总药量的78.34%;其次为尿排泄,占总药量的2.32%,胆汁最低为0.10%。α-倒捻子素灌胃给药后原型药物主要通过粪便和尿途径排出体外,未发现其他代谢产物。结论: 所建立的HPLC-UV测定方法符合方法学考核要求,适用于大鼠灌胃α-倒捻子素后生物样品中原型药物的测定及其排泄研究;α-倒捻子素灌胃给药后主要以粪排泄为主,以原型药物排出体外。

Objective: To investigate the characteristics of α-mangostin excretion in rats after intragastric administration. Methods: Urine,feces and bile were collected after a single oral dose of 16.4 mg·kg^-1 α-mangostin to rats within 48 h,48 h,and 24 h,respectively,and a high performance liquid chromatography (HPLC)with UV detection was developed to study the concentration of α-mangostin in the biological samples.The biological samples were treated by liquid-liquid extraction with methanol.The chromatographic separation was accomplished on a reversed-phase C₁₈ (250 mm×4.6 mm,5 μm)column using methanol-water (95:5)as the mobile phase at a flow rate of 1.0 mL·min^-1 and the ultraviolet detection wavelength was set at 317 nm. Results: When the concentration of α-mangostin in bile was at 0.12-120 μg·mL^-1,in urine at 0.16-160 μg·mL^-1,in fecal at 0.26-5200 μg·mL^-1,its peak area and quality had linear correlation,and the correlation coefficients were greater than 0.999 by the HPLC-UV method.The accumulation excretion amount of α-mangostin in feces and urine within 48 h were 78.34% and 2.32%,respectively,and 0.10% in bile within 24 h.These data indicated that α-mangostin was mainly excreted in feces,followed by urine,and least in bile.By intragastric administration,the prototype drug of α-mangostin was mainly excreted through defecation and urination,and no other metabolites were found. Conclusion: The method is satisfactory by methodology verification and suitable for determination of α-mangostin in rat biological samples and the study of its cumulative excretion.α-Mangostin is mainly excreted in feces by the form of prototype drug in rats after intragastric administration.