HPLC-MS/MS法考察水黄皮素在SD大鼠体内的药代动力学特征  

Investigate of Pharmacokinetics of Karanjin in SD Rats by HPLC-MS/MS

作　　者：赵映淑 王巨才 曹锋 刘春 陈叶兰 Zhao Yingshu;Wang Jucai;Cao Feng;Liu Chun;Chen Yelan(Center for Drug Safety Evaluation of Hainan Institute for Drug Control,Haikou 570216,China;Hainan Institute of Medicine Co.,Ltd.,Haikou 571100,China)

机构地区：[1]海南省药品检验所安全性评价研究中心,海口570216 [2]海南药物研究所有限责任公司,海口571100

出　　处：《中国药事》2024年第1期82-88,共7页Chinese Pharmaceutical Affairs

基　　金：海南省自然科学基金面上项目(编号819MS105)。

摘　　要：目的:建立大鼠血浆中水黄皮素的定量分析方法,并对其药代动力学进行研究。方法:通过灌胃给予SD大鼠水黄皮素(10 mg·kg^(-1)),血浆样品经蛋白沉淀法处理后进行HPLC-MS/MS定量分析,以五味子醇甲为内标,采用Agilent Poroshell 120 EC-C_(18)(50 mm×3.0 mm,2.7μm)色谱柱,乙腈(A)-0.1%甲酸溶液(B)为流动相,流速0.3 mL·min^(-1),梯度洗脱;采用电喷雾离子源(ESI),正离子多反应监测模式(MRM)扫描,水黄皮素[M+H]^(+)m/z 293.1→277.0,五味子醇甲[M+H]^(+)m/z433.2→384.2;使用DAS软件计算相关药代动力学参数。结果:在1.5625~1600 ng·mL^(-1)浓度范围内,水黄皮素线性关系良好(r=0.9997),定量下限为1.5625 ng·mL^(-1),精密度RSD和准确度RE均小于20%;低、中、高质控样品精密度RSD和准确度RE均小于15%,提取回收率在91.70%~100.28%,基质效应在88.35%~97.55%,稳定性RSD均小于15%。水黄皮素在雌性SD大鼠体内T_(max)、t_(1/2)、C_(max)和AUC_(0→t)分别为3 h、1.95 h、1214.85 ng·mL^(-1)和11920.43 ng·mL^(-1)·h;在雄性SD大鼠体内T_(max)、t_(1/2)、C_(max)和AUC_(0→t)分别为3 h、1.19 h、1221.57 ng·mL^(-1)和9983.40 ng·mL^(-1)·h。结论:所建方法符合生物样品定量分析的基本要求,可用于水黄皮素在大鼠血浆中的含量测定及其药代动力学评价;水黄皮素在雌性SD大鼠体内的生物利用度更高。Objective:To establish a quantitative analysis method for the determination of karanjin in rat plasma and study its pharmacokinetics.Methods:SD rats were intragastrically administered with karanjin(10 mg·kg^(-1)).The plasma samples were pretreated by protein precipitation method and then detected quantitatively by HPLC-MS/MS.Schisandrin was employed as an internal standard.The separation was performed on an Agilent Poroshell 120 EC-C_(18)(50 mm×3.0 mm,2.7μm)column with acetonitrile(A)-0.1%methanoic acid solution(B)as mobile phase at a flow rate of 0.3 mL·min-1.Electrospray ionization(ESI)source and positive ion multiple reaction monitoring(MRM)mode were used for scanning,and the results showed that karanjin[M+H]^(+)m/z 293.1→277.0,schisandrin[M+H]^(+)m/z 433.2→384.2;the pharmacokinetic parameters were calculated by DAS software.Results:In the range of 1.5625-1600 ng·mL^(-1),karanjin showed a good liner relationship in plasma(r=0.9997),with a low limit of quantification of 1.5625 ng·mL^(-1),precision(RSD)and accuracy(RE)were less than 20%.The precision RSD and accuracy RE of low medium and high quality control samples were less than 15%.The T_(max),t_(1/2),C_(max)and AUC_(0→t)of female SD rats were 3 h,1.95 h,1214.85 ng·mL^(-1)and 11920.43 ng·mL^(-1)·h respectively,while that of male rats were 3 h,1.19 h,1221.57 ng·mL^(-1)and 9983.40 ng·mL^(-1)·h respectively.Conclusion:The established method meets the basic requirements of quantitative analysis of biological samples,and can be used for the content determination and pharmacokinetic evaluation of karanjin in rat plasma.The bioavailability of karanjin in female SD rats is higher.

关 键 词：水黄皮素 含量测定 液质联用 SD大鼠 血浆 药代动力学 

分 类 号：R917[医药卫生—药物分析学]