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[摘要]
目的 建立高效液相色谱/四极杆-静电场轨道阱高分辨质谱(HPLC-Q-HR/MS)方法,研究大黄素在正常与脑缺血大鼠体内的药动学规律。方法 采用HPLC-Q-HR/MS内标法测定大黄素血药浓度,色谱柱为XBridgeTM C18柱(150 mm×2.1 mm,5 μm),柱温30 ℃;流动相为3 mmol/L乙酸铵-甲醇,梯度洗脱,梯度洗脱程序为0~2 min,30%甲醇;2~10 min,30%~60%甲醇;10~13 min,60%~30%甲醇;体积流量为0.3 mL/min;进样体积为5 μL;质谱条件:离子源为加热电喷雾离子化源(HESI),扫描方式为全扫模式,负离子模式检测。以DAS 3.0软件拟合计算药动学参数。结果 大黄素在正常与脑缺血大鼠血浆中的主要药动学参数分别为AUC0-∞(605.63±163.66)、(1 107.78±191.11)ng·h/mL,Cmax(81.96±20.72)、(91.65±16.82)ng/mL,VZ/F(851.03±97.30)、(1 051.87±119.88)L/kg,t1/2(10.31±1.61)、(23.13±3.56)h,tmax(0.75±0.22)、(0.75±0.16)h。结论 该法操作简便、分析速度快速、灵敏,适用于大黄素在大鼠体内的药动学研究。
[Key word]
[Abstract]
Objective To establish a method for determination of emodin in rat plasma by HPLC/Q-Exactive HR/MS, and to study the pharmacokinetics of emodin in normal rats and cerebral ischemia rats. Methods The plasma concentration of emodin was determined by HPLC/Q-Exactive HRMS method with internal standard method. Emodin was eluted on a XBridgeTM C18 (150 mm×2.1 mm, 5 μm) column with temperature at 30 ℃. The mobile phase consisted of 3 mmol/L ammonium acetate and methanol, with a gradient program as follows: 0~2 min (30% methanol), 2—10 min (30%—60% methanol), 10—13 min (60%—30% methanol). The flow rate was 0.3 mL/min, and the injection volume was 5 μL. MS experiments were coupled with the HPLC via HESI source operated in negative ionization full-scan mode. The pharmacokinetic parameters were calculated by the software of DAS 3.0. Results The main pharmacokinetic parameters of emodin in normal rats and cerebral ischemia rats were as follows: AUC0-∞ were (605.63±163.66) and (1 107.78±191.11) ng·h/mL, Cmax were (81.96±20.72) and (91.65±16.82) ng/mL, VZ/F were (851.03±97.30) and (1 051.87±119.88) L/kg, t1/2 were (10.31±1.61) and (23.13±3.56) h, tmax were (0.75±0.22) and (0.75±0.16) h. Conclusion The method is simple, accurate, fast, sensitive, and suitable for the pharmacokinetic study of emodin in rats.
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[基金项目]
国家自然科学基金资助项目(81274179);河南省教育厅科学技术研究重点项目(14B360004)