LC-MS/MS法测定东北黄精灌胃后大鼠血浆中3种皂苷类化合物含量及其药代动力学研究  

Determination of Three Saponins in Rat Plasma after Intragastric Administration of Polygonatum sibiricum by LC-MS/MS and Its Pharmacokinetic Study

作　　者：崔芙岩 黄金月 姜佳欣 唐檬 马鹰 郑时嘉 于纯淼[1] 王志刚[1] 杨波[1] CUI Fuyan;HUANG Jinyue;JIANG Jiaxin;TANG Meng;MA Ying;ZHENG Shijia;YU Chunmiao;WANG Zhigang;YANG Bo(Heilongjiang University of Chinese Medicine,Harbin 150040,China;Harbin Tianwenshan Agricultural Comprehensive Development Co.,Ltd.,Harbin 150300,China)

机构地区：[1]黑龙江中医药大学,黑龙江哈尔滨150040 [2]天问山农业综合开发股份有限公司,黑龙江哈尔滨150300

出　　处：《中医药学报》2021年第12期23-28,共6页Acta Chinese Medicine and Pharmacology

基　　金：黑龙江省应用技术研究与开发计划项目(GA20C017)。

摘　　要：目的:采用LC-MS/MS法测定中药黄精灌胃后大鼠血浆中人参皂苷Rb_(1)、薯蓣皂苷和菝葜皂苷元的含量,并将此方法应用于大鼠口服东北黄精后皂苷类化合物的代谢动力学研究。方法:采用96孔板进行大鼠血浆生物样品提取,提高样品的处理效率,以A甲醇-B 0.1%甲酸溶液(70∶30)为流动相进行等度洗脱,在正离子模式下进行检测,采用多级反应检测(Multiple Reaction Monitoring,MRM)法。用于定量分析的离子反应对分别为m/z 1131.6→365.7(人参皂苷Rb_(1))、m/z 890.5→721.3(薯蓣皂苷)、m/z 439.7→417.6(菝葜皂苷元)、m/z 491.5→425.3(甘草次酸,内标)。结果:3种皂苷化合物的大鼠血浆样品测定方法的定量范围为5~220 ng/mL,线性相关系数r>0.999,精密度RSD<8.8%,回收率为82.34%~89.41%,基质效应为90.23%~91.34%。黄精灌胃后大鼠血浆中人参皂苷Rb_(1)、薯蓣皂苷、菝葜皂苷元的达峰时间t_(max)分别为(2.03±0.32)h、(1.91±0.54)h、(1.16±0.19)h,半衰期t_(1/2)分别为(8.57±0.53)h、(7.34±0.68)h、(6.85±0.52)h,最大血药浓度C_(max)分别为(90.37±21.08)ng/mL、(55.21±20.12)ng/mL、(136.27±39.05)ng/mL,药时曲线下面积AUC_(0~24)分别为(1095.83±87.36)(ng·h)/mL、(735.65±64.36)(ng·h)/mL、(1648.96±103.26)(ng·h)/mL。结论:该方法高效、快速、灵敏,适用于中药黄精灌胃后大鼠血浆中3种皂苷类物质的药代动力学研究,本研究方法及结果将为东北黄精体内作用物质基础研究及临床应用提供重要参考。Objective:To determine the contents of ginsenoside Rb_(1),dioscin and sarsasapogenin in rats plasma after oral administration of Polygonatum sibiricum by LC-MS/MS method,and to study the pharmacokinetic behavior of saponins from Polygonatum sibiricum.Methods:Rat plasma was extracted with 96-well plate to improve the efficiency of process.A mixture of A methanol-B 0.1% formic acid(70∶30)was used as mobile phase for isocratic elution.The detection was carried out in positive mode by multiple reaction monitoring(MRM).The ionic reaction pairs for quantitative analysis were m/z 1131.6→365.7(ginsenoside Rb_(1)),m/z 890.5→721.3(dioscin),m/z 439.7→417.6(sarsaparinin)and m/z 491.5→425.3(glycyrhizic acid,internal standard),respectively.Results:The quantitative range of the three saponins in rat plasma samples was 5~220 ng/mL,all linear correlation coefficients were all greater than 0.999,the precisions(RSD)were all less than 8.8%,the recovery was 82.34~89.41%,and the matrix effect was 90.23~91.34%.The t_(max) of ginsenoside Rb_(1),dioscin and sarsaparigenin in plasma of rats was(2.03±0.32)h,(1.91±0.54)h and(1.16±0.19)h,respectively.The t_(1/2) was(8.57±0.53)h,(7.34±0.68)h and(6.85±0.52)h,respectively.The C_(max) was(90.37±21.08)ng/mL,(55.21±20.12)ng/mL and(136.27±39.05)ng/mL,respectively.The AUC_(0~24) was(1095.83±87.36)(ng·h)/mL,(735.65±64.36)(ng·h)/mL and(1648.96±103.26)(ng·h)/mL,respectively.Conclusion:The method is efficient,rapid and suitable for the study of pharmacokinetics of three saponins in plasma of rats after oral administration of Polygonatum sibiricum.The results will provide important reference for the study of active components of Polygonatum sibiricum in vivo and for the clinical application of the herb.

关 键 词：黄精 人参皂苷RB 薯蓣皂苷 菝葜皂苷元 

分 类 号：R284.1[医药卫生—中药学]