目的 用超高效液相色譜-質(zhì)譜聯(lián)用技術(shù)(UPLC-MS/MS)研究大鼠ig 給藥樺木酸的血漿藥動學。方法 大鼠頸靜脈插管后ig 給予250 mg/kg 的樺木酸棉籽油懸濁液(100 mg/mL),于給藥前和給藥后0.08、0.17、0.33、0.5、1、2、4、6、8、12、24 和48 h 時取血,血液樣品經(jīng)醋酸乙酯提取,對甲苯磺酰異氰酸酯(PTSI)柱前衍生化后,采用UPLC-MS/MS 法測定大鼠血漿中樺木酸的量。結(jié)果 樺木酸以250 mg/kg 劑量大鼠ig 給藥以后,樺木酸在(1.2±0.4)h 達到最大血藥濃度值(158.5±26.8)ng/mL,24 h 后基本檢測不到。藥時曲線下面積AUC_0-24 和AUC_0-∞分別為(292.41±100.6)ng·h/mL 和(331.45±113.3)ng·h/mL,半衰期(t_1/2)和平均滯留時間(MRT)分別為(3.8±1.4)h 和(4.8±2.1)h。結(jié)論 UPLC-MS/MS 方法可成功用于經(jīng)口給藥樺木酸大鼠血漿藥動學研究,樺木酸的口服吸收極差。

Objective The pharmacokinetic study of betulinic acid in rat plasma after oral administration of betulinic acid was studied by UPLC-MS/MS. Methods The rats were orally administered with betulinic acid (100 mg/mL suspended in cottonseed oil) at the dose of 250 mg/kg after taken jugular vein cannulation. The blood samples were collected before administration and 0.08 h, 0.17 h, 0.33 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h after administration. The plasma sample was extracted with ethyl acetate and derivatized with p-toluenesulfonylisocyanate (PTSI), and the concentration of betulinic acid was determined using UPLC-MS/MS. Results After oral dosing, betulinic acid reached the maximum concentration of (158.5 ± 26.8) ng/mL at (1.2 ± 0.4) h, and could not be detectable after 24 h. AUC_0-24 and AUC_0-∞were (292.41 ± 100.6) and (331.45 ± 113.3) ng·h/mL, respectively. t_1/2 and MRT were (3.8 ± 1.4) and (4.8 ± 2.1) h, respectively. Conclusion The UPLC-MS/MS method is successfully applied to the pharmacokinetic study of betulinic acid in rat plasma. The absorption of betulinic acid is extremely low.

黑龍江省自然科學基金項目(C201101);黑龍江中醫(yī)藥大學優(yōu)秀創(chuàng)新人才支持計劃