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目的建立大鼠血浆中苦参酮UPLC-MS/MS测定方法,研究大鼠静脉、口服苦参酮后的体内药动学。方法采用ACQUITY UPLC~ HSS T3 C_(18)色谱柱,乙腈-0.1%甲酸水为流动相,梯度洗脱,流速0.2 mL·min~(-1),待测血浆样品采用乙酸乙酯液液萃取法制备。MS/MS采用电喷雾离子化电离源(ESI),多反应离子监测(MRM),负离子方式检测,芦丁为内标。监测离子对分别为m/z 437.2→161.1(苦参酮)和m/z 609.3→300.3(芦丁)。DAS 2.0软件处理数据。结果苦参酮在0.1~1000 ng·mL~(-1)的浓度范围内有良好的线性关系(r~2=0.9965);精密度<12.9%,准确度在-7.4%~11.7%之间,平均提取回收率>79.2%。苦参酮静脉给药后T_(1/2z)为(4.0±0.3)h,AUC_(0→∞)为(0.64±0.26)μg·mL~(-1)·h,MRT_(0→∞)为(3.0±0.4)h;口服后T_(1/2z)为(5.6±2.1)h,T_max为(1.7±1.2)h,AUC_(0→∞)为(1.4±0.3)μg·mL~(-1)·h,MRT_(0→∞)为(6.1±1.0)h;苦参酮在大鼠体内的绝对生物利用度约10.7%。结论所建立的UPLC-MS/MS分析方法简便、快速、灵敏、准确,可用于苦参酮大鼠体内药物动力学研究,苦参酮大鼠口服绝对生物利用度偏低。
OBJECTIVE: To establish a method for the determination of kushenin in rat plasma by UPLC-MS / MS and to study the pharmacokinetics of venous and oral matrine in rats. Methods The ACQUITY UPLC ~ HSS T3 C 18 column and acetonitrile-0.1% formic acid water were used as the mobile phase and the gradient elution was performed at a flow rate of 0.2 mL · min -1. The plasma samples were extracted with ethyl acetate solution Preparation by extraction. MS / MS electrospray ionization ionization source (ESI), multiple reaction ion monitoring (MRM), negative ion detection, rutin as an internal standard. The monitored ion pairs were m / z 437.2 → 161.1 (matrine) and m / z 609.3 → 300.3 (rutin), respectively. DAS 2.0 software processes the data. Results There was a good linear relationship between the concentration of matrine and 0.1 ~ 1000 ng · mL ~ (-1) (r ~ 2 = 0.9965). The precision was <12.9% and the accuracy was between -7.4% ~ 11.7% , The average extraction recovery rate> 79.2%. The T_ (1 / 2z) was (4.0 ± 0.3) h and the AUC_ (0 → ∞) was (0.64 ± 0.26) μg · mL ~ (-1) h after MRS administration. MRT_ (0 → ∞) (1.4 ± 0.3) μg · mL ~ (-1), and the mean T_ (1 / 2z) was (5.6 ± 2.1) -1) · h, and MRT_ (0 → ∞) was (6.1 ± 1.0) h. The absolute bioavailability of matrine in rats was about 10.7%. Conclusion The established UPLC-MS / MS method is simple, rapid, sensitive and accurate and can be used to study the pharmacokinetics of the body in rats. The absolute bioavailability of oral orally administered matrine in rats is low.