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本文建立了一种快速、灵敏的LC-MS法用于检测小鼠血浆中的高乌甲素浓度。采用ESI源和多反应监测(MRM)的方式进行检测,所选用的高乌甲素和内标延胡索乙素的反应离子对分别为m/z 585→535和m/z 356→m/z 192。该方法在3.0～2 000.0 ng·mL-1浓度内线性关系良好,定量下限为3.0 ng·mL-1,日内和日间精密度(RSD)均小于9.9%,准确度(RE)在±4.8%之内。氢溴酸高乌甲素分别以1.0、2.0和4.0 mg·kg-1单剂量静脉注射给予小鼠后,t1/2分别为0.47、0.48和0.49 h,AUC0-t分别为55.5、110.5和402.9 ng·h·mL-1。实验结果表明,氢溴酸高乌甲素单剂量静脉注射给予小鼠后,在低剂量(1.0～2.0 mg·kg-1)范围内其药动学行为符合线性动力学特征,当给药剂量(2.0 mg·kg-1)增大至4.0 mg·kg-1时,AUC增加至约4倍,而Vz和CL却显著降低,呈现非线性动力学特征,可能与高浓度下药物血浆蛋白结合率的降低有关。
In this paper, a rapid and sensitive LC-MS method was developed for the determination of lappaconite concentration in mouse plasma. The ESI source and multi-reaction monitoring (MRM) were used for the detection. The reaction ion pairs of lappaconitine and internal standard tetrahydropalmatine were m / z 585 → 535 and m / z 356 → m / z 192, respectively . The linearity was 3.0-2000.0 ng · mL-1 with a lower limit of quantification of 3.0 ng · mL-1. The RSD was less than 9.9% and the accuracy (RE) was within ± 4.8 %within. After a single dose of 1.0, 2.0 and 4.0 mg · kg-1 of lappaconite hydrobromide were administered to mice, t1 / 2 was 0.47, 0.48 and 0.49 h, AUC0-t were 55.5, 110.5 and 402.9 ng · h · mL-1. The experimental results showed that the pharmacokinetic behavior of Lappaconitine hydrobromide single-dose intravenous injection in mice in the low dose (1.0 ~ 2.0 mg · kg-1) range in line with the linear kinetic characteristics, when the dose (2.0 mg · kg-1) increased to 4.0 mg · kg-1, AUC increased to about 4-fold, while Vz and CL were significantly reduced, showing a nonlinear kinetic characteristics may be associated with high concentrations of drug plasma protein binding Rate reduction related.