本文選題：伊曲康唑　切入點：異構體　出處：《中國藥科大學學報》2015年03期

【摘要】：采用LC-MS/MS法研究伊曲康唑4種異構體在大鼠體內的藥代動力學差異。大鼠分別灌胃伊曲康唑4種異構體后,用LC-MS/MS法測定血漿中伊曲康唑4種異構體的代謝及主要代謝產物羥基伊曲康唑的生成情況。采用乙腈直接沉淀蛋白,色譜柱為Durashell HILIC柱(100 mm×2.1 mm,5.0 m),流動相中有機相為甲醇-乙腈(1∶1),水相為含5 mmol/L乙酸銨和0.2%乙酸的超純水,以0.5 m L/min的流速進行梯度洗脫,總洗脫時間為5.5 min。掃描方式為選擇反應監(jiān)測(MRM),采用正離子方法檢測。大鼠單次灌胃給予15 mg/kg伊曲康唑4種不同異構體后,2S,4R,2R型伊曲康唑和2S,4R,2S型伊曲康唑在大鼠體內的羥基代謝物的生成量明顯高于(2R,4S,2R)型伊曲康唑和(2R,4S,2S)型伊曲康唑(P0.001)。此外,伊曲康唑在大鼠中存在明顯的雌雄差異,雌性大鼠體內的峰濃度(cmax)和藥時曲線下面積(AUC0-∞)明顯高于雄鼠,半衰期(t1/2)明顯長于雄鼠,消除較雄鼠慢。通過檢測伊曲康唑4種異構體原藥及相應的羥基代謝物在大鼠體內的經時過程,表明不同異構體在大鼠體內的藥代動力學行為存在明顯的代謝差異和性別差異。
[Abstract]:The pharmacokinetics of four isomers of itraconazole in rats was studied by LC-MS/MS. The metabolism of four isomers of itraconazole and the formation of its main metabolite hydroxyitraconazole in plasma were determined by LC-MS/MS method. The protein was precipitated by acetonitrile. The chromatographic column was Durashell HILIC column (100mm 脳 2.1mm), the organic phase in the mobile phase was methanol-acetonitrile (1: 1), the water phase was ultrapure water (containing 5 mmol/L ammonium acetate and 0.2% acetic acid), and the gradient elution was carried out at the flow rate of 0.5 m L/min. The total elution time was 5.5 mins. The scanning method was selected to monitor the reaction and detected by positive ion method. Rats were given 4 different isomers of itraconazole for 15 mg/kg by single gavage. The production of hydroxyl metabolites was significantly higher than that of itraconazole and itraconazole (P 0.001). Itraconazole was significantly different between male and female in rats. The peak concentration of itraconazole in female rats was significantly higher than that in male rats, and the area under the drug time curve (AUC0- 鈭，

本文編號：1697493