补骨脂中13种活性成分在正常和酒精性肝病大鼠体内的药代动力学比较研究

Comparative Study on Pharmacokinetics of 13 Active Ingredients of Psoraleae Fructus in Normal and Alcoholic Liver Disease Rats

关键词:  补骨脂  肝毒性  酒精性肝病  UHPLC-MS/MS  药代动力学

Key words:  psoraleae fructus  hepatotoxicity  alcoholic liver disease  UHPLC-MS/MS  pharmacokinetics.

摘要:

目的 采用超高效液相色谱-串联质谱(UHPLC-MS/MS)技术探究补骨脂中补骨脂素、异补骨脂素、补骨脂酚、补骨脂查尔酮、补骨脂二氢黄酮甲醚、补骨脂宁、补骨脂定、补骨脂甲素、补骨脂乙素、异补骨脂二氢黄酮、新补骨脂异黄酮、巴库查尔酮和Corylifol A 13种成分在正常大鼠和酒精性肝病（ALD）模型大鼠的体内的药动学。方法 使用Hypersil GOLD C18色谱柱（2.1×100 mm，1.9 μm）；流动相为水-乙腈；流速0.2 mL·min-1；柱温为40 ℃。在成功建立SD大鼠的ALD模型的基础上，按1.07 g/kg的给药剂量灌胃补骨脂生药溶液，采用UHPLC-MS/MS测定血浆中13主要入血成分血药浓度，药代动力学软件 DAS 3.0 计算各成分的药代动力学参数。结果 SD大鼠在患ALD后服用补骨脂，补骨脂酚、补骨脂二氢黄酮甲醚、补骨脂甲素、补骨脂乙素、新补骨脂异黄酮、Corylifol A 等入血成分体内AUC、Cmax显著升高，结果提示补骨脂相关成分入血暴露水平增加。结论 机体患ALD时服用补骨脂，可能导致补骨脂相关肝毒性成分体内暴露量增加，提示补骨脂在ALD患者临床用药时合理调整剂量。

Abstract:

OBJECTIVE The pharmacokinetics of thirteen ingredients of Psoraleae Fructus, including psoralen, isopsoralen, bakuchiol, bavachalcone, bavachinin, corylin, psoralidin, bavachin, isobavachalcone, isobavachin, neobavaisoflavone, bakuchalcone and corylifol A in normal rats and alcoholic liver disease (ALD) model rats were explored by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) technology. METHODS A Thermo Fisher Scientific Hypersil GOLD C18 column (2.1×100 mm,1.9 μm) was employed; the mobile phase was composed of water and acetonitrile; the flow rate was 0.2 mL.min^-1; and the column temperature was maintained at 40℃. On the basis of the successful establishment of the ALD model in male SD rats, the crude drug solution of Psoraleae Fructus was administered by gavage at a dose of 1.07 g/kg. The plasma concentrations of 13 major components were determined by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), and the pharmacokinetic parameters of each component were calculated using DAS 3.0 software. RESULTS After male SD rats developed ALD and were administered Psoraleae Fructus, the AUC and Cmax of bakuchiol, bavachinin, isobavachalcone, neobavaisoflavone, isobavachin, corylifol A, etc significantly increased, indicating an elevated blood exposure level of Psoralea Fructus - related components. CONCLUSION When male organisms with ALD are administered Psoraleae Fructus, it may lead to an increase in the intake of Psoraleae Fructus -related hepatotoxicity components into the bloodstream, suggesting that the dosage of Psoraleae Fructus should be rationally adjusted during clinical medication for ALD patients.