牛黄解毒片及黄芩大鼠给药后血浆中黄芩特征成分药代动力学的比较研究  

Comparative pharmacokinetics of characteristic components of Scutellariae Radix in rats plasma after oral administration of Scutellariae Radix and Niuhuang Jiedu tablets

作　　者：刘玥昕 宋敏[2] 杭太俊[2] 吴骁 LIU Yue-xin;SONG Min;HANG Tai-jun;WU Xiao(TIPR Pharmaceutical Responsible Co.,Ltd.,Tianjin 300301,China;Department of Pharmaceutical Analysis,China Pharmaceutical University,Nanjing 210009,China;Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]天津药物研究院药业有限责任公司,天津300301 [2]中国药科大学药物分析系,南京210009 [3]南京中医药大学,南京210023

出　　处：《药物分析杂志》2024年第7期1202-1211,共10页Chinese Journal of Pharmaceutical Analysis

基　　金：国家自然科学基金资助项目(82104523);江苏省自然科学基金青年基金资助项目(BK20200843);南京中医药大学国家自然科学基金青年科学基金配套经费项目(XPT82104523)。

摘　　要：目的:建立高效液相色谱-串联质谱法(HPLC-MS/MS法)同时检测大鼠血浆中6个黄芩特征成分(黄芩素、黄芩苷、汉黄芩素、汉黄芩苷、白杨素及千层纸素A)的含量,比较大鼠牛黄解毒片及黄芩给药后黄芩特征成分在大鼠体内药代动力学行为的差异。方法:2组大鼠分别灌胃给予牛黄解毒片混悬液250 mg·kg-1或处方等量的黄芩饮片提取液,收集不同时间点血浆样本,以柚皮素为内标,经甲醇沉淀蛋白后,采用Inertsil C8-3(150 mm×4.6 mm,5μm)色谱柱,以0.1%甲酸水溶液(A)-0.1%甲酸甲醇溶液(B)为流动相,线性梯度洗脱,流速1.0 mL·min^(-1),柱温35℃,采用电喷雾离子源(ESI),正离子扫描,多反应监测模式(MRM)检测黄芩特征成分,并计算药代动力学参数。结果:黄芩素、黄芩苷、汉黄芩素、汉黄芩苷、白杨素及千层纸素A 6个黄芩特征成分均在5~500 ng·mL^(-1)范围内线性关系良好,准确度为88.43%~108.6%,批间精密度及批内精密度均<15%,基质效应和血浆样品稳定性均可满足生物样品分析要求。大鼠灌胃黄芩饮片提取液及牛黄解毒片混悬液后,血浆中检测出黄芩苷及汉黄芩苷2个主要成分;与单味黄芩组比较,牛黄解毒片组给药后大鼠血浆中汉黄芩苷的AUC0-t、黄芩苷与汉黄芩苷的Cmax均显著增加,Tmax显著缩短。结论:建立的方法能同时测定黄芩6个特征成分,且专属性强,灵敏度高,适用于大鼠血浆药代动力学研究。牛黄解毒片复方配伍增强了黄芩的特征成分在大鼠体内的吸收利用,改变了黄芩特征成分的药代动力学行为。Objective:To establish an HPLC-MS/MS method for the simultaneous determination of six characteristic components of Scutellariae Radix including baicalein,baicalin,wogonin,wogonoside,chrysin and oroxylin A in rat plasma,and to compare their pharmacokinetic profiles after oral administration of Scutellariae Radix and Niuhuang Jiedu tablets(NHJDT)to rats.Methods:Rats were given 250 mg·kg-1 of NHJDT suspension or the prescribed equivalent amount of Scutellariae Radix aqueous extract,and plasma samples were collected at different time intervals.Naringenin was used as internal standard.After precipitated with methanol,the plasma samples were separated on an Inertsil C8-3(150 mm×4.6 mm,5μm)column by linear gradient elution with 0.1%formic acid solution(A)-0.1%formic acid-methanol(B)as mobile phase.The flow rate was 1.0 mL·min^(-1),and the column temperature was 35℃.The analytes were detected by tandem mass spectrometry with the electrospray ionization(ESI)source combined with multiple reaction monitoring(MRM)mode in positive ion mode.The pharmacokinetic parameters were calculated and statistically analyzed.Results:The six characteristic components of Scutellariae Radix were all in good linear relationships in the range of 5-500 ng·mL^(-1).The RSDs for accuracy test were in the range of 88.43%-108.6%,and the RSDs for inter-batch and intra-batch precision tests were all below 15%.The matrix effect and plasma stability met the requirements of methodology validation in biological sample analysis.Baicalin and wogonoside were the major components detected in rat plasma after oral gavage of Scutellariae Radix aqueous extract and NHJDT suspension.The AUC0-t of wogonoside was significantly increased in NHJDT group compared with Scutellariae Radix group.Furthermore,the Cmax of wogonoside and baicalin were significantly increased while the Tmax was decreased after NHJDT suspension administration.Conclusion:This method is specific and sensitive for the determination of six characteristic components of Scutellariae Radix,and

关 键 词：黄芩 牛黄解毒片 黄芩苷 汉黄芩苷 高效液相色谱-串联质谱法 比较药代动力学 大鼠血浆 

分 类 号：R917[医药卫生—药物分析学]