超高效液相色谱-串联质谱法测定大黄对大鼠CYP450酶活力的影响  

Effect of Rheum palmatum L. determination by UPLC-MS/MS on CYP450 activity in rats

作　　者：胡思一[1] 叶冬青 温从丛 包箐箐 HU Si-yi;YE Dong-qing;WEN Cong-cong;BAO Qing-qing(Pharmacy,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou ,Zhejiang 325000,Chinn)

机构地区：[1]温州医科大学附属第一医院药学部,浙江温州325000 [2]温州医科大学实验动物中心,浙江温州325035

出　　处：《中国卫生检验杂志》2019年第18期2189-2193,2208,共6页Chinese Journal of Health Laboratory Technology

基　　金：温州市科技局项目(Y20130247)

摘　　要：目的超高效液相色谱-串联质谱法(UPLC-MS/MS)同时测定大鼠血浆中5种探针药物(安非他酮、美托洛尔咪达唑仑、非那西丁和甲苯磺丁脲)及其代谢产物(羟基安非他酮、羟基美托洛尔、1-羟基咪达唑仑、对乙酰氨基酚和羟基甲苯磺丁脲),评价大黄对大鼠CYP450酶活性影响。方法将大鼠随机分成大黄组和对照组2组。大黄组灌胃给予大黄14 d,对照组灌胃给予生理盐水14 d。5种探针药物通过灌胃给予大鼠,用UPLC - MS/MS测定血浆药物浓度。结果大黄组和对照组对比结果中,安非他酮、美托洛尔、非那西丁和甲苯磺丁脲药代动力学差异均有统计学意义(P<0.05)。大黄组与对照组对比,美托洛尔AUC(0-t)降低(P <0.05),Cmax升高(P <0.05),其代谢产物羟基美托洛尔变化趋势与母药相似;非那西汀AUC(0-t)升高(P<0.01),CL降低(P <0.01),Cmax升高(P<0.01),其代谢产物对乙酰氨基酚变化趋势与母药相似;甲苯磺丁脲AUG(0-t)升高(P<0.01),CL降低(P <0.01),Cmax升高(P<0.01),其代谢产物对羟基甲苯磺丁脲变化趋势与母药相似。结论大鼠灌胃大黄可能会诱导大鼠CYP2D6酶活性,可能会抑制大鼠CYP1A2、CYP2C9酶活性。Objective A specific ultra-performance liquid chromatography tandem mass spectrometry ( UHPLC-MS/MS ) method has been established for the simultaneous determination of bupropion,metroprolol ,midazolam,phenacetin,tolbutamide and their metabolites ( hydroxyburpropion, hydroxymetoprolol, 1-hydroxymidazolam,acteminophen and hydroxytolbutamide) in rat plasma, to evaluate the effect of rheum palmatum L. on rat CYP450 enzyme activity. Methods The rats were randomly divided into Rheum palmatum L. group and control group. The Rheum palmatum L. group rats were given Rheum palmatum L. decoction by. intragastric administration, and the control group was given saline solution by intragastric administration. Results Rheum palmatum L. group was compared to the control group,and there was statistical sigmificance on the pharmaco- kinetic difference for bupropion, metroprolol ,phenacetin and tolbutamide ( P <0.05). Compared with the control group, the AUCo . 1 of metoprolol decreased (P<0. 05),CL increased (P<0. 05),and the metabolite hydroxymetoprolol changed trend similarly to the parent drug;AUC(0-t) of phenacetin increased (P<0.01), CL decreased (P<0.01), Cmax inereased (P < 0.01),and its metabolite acetaminophen changed similarly to the parent drug;tolbutamide AUC(0-t) increased (P <0.01), CL decreased (P<0.01),Cmax increased (P<0. 01), and the metabolites of hydroxyolbutamide showed similar trends with the parent drug. Conclusion Rheum palmatum L. may induce CYP2D6 enzyme activity in rats, and inhibit the activity of CYP1 A2 and CYP2C9 in rats.

关 键 词：细胞色素P450 探针药 大黄 超高效液相-质谱联用法 

分 类 号：R96[医药卫生—药理学]