基于UPLC-Orbitrap MS/MS对比分析女贞子不同炮制品中多成分药代动力学特征  

Comparative pharmacokinetic characterization of multi-components in different artifacts of Ligustri Lucidi Fructus based on UPLC-Orbitrap MS/MS

作　　者：赵灿楠 孙淑仃 郑历史 赵迪[1,2,3] 李焕茹 冯素香 ZHAO Can-nann;SUN Shu-ding;ZHENG Li-shi;ZHAO Di;LI Huan-ru;FENG Su-xiang(Henan University of Chinese Medicine,Zhengzhou 450046,China;Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province&Education Ministry of P.R.,Zhengzhou 450046,China;Henan Engineering Research Center of Modern Chinese Medicine Research,Development and application,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学,郑州450046 [2]呼吸疾病中医药防治省部共建协同创新中心,郑州450046 [3]河南省现代中药研发与应用工程研究中心,郑州450046

出　　处：《药物分析杂志》2024年第12期2011-2022,共12页Chinese Journal of Pharmaceutical Analysis

基　　金：国家自然科学基金项目(No.82374041);河南省中医药科学研究专项课题(2023ZY1029)。

摘　　要：目的:建立血浆中红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷、女贞苷G13的超高效液相色谱-质谱分析方法,探究女贞子、酒女贞子、醋女贞子、盐女贞子、清蒸女贞子5种不同炮制品在大鼠体内的药代动力学特征差异。方法:SPF级雄性SD大鼠随机分为6组,分别灌胃给予女贞子不同炮制品水提液4.2 g·kg^(-1)(以生药量计),以京尼平苷为内标物,血浆样品经甲醇沉淀蛋白,采用UPLC-MS/MS负离子SIM模式测定不同时间点大鼠血浆中红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷以及女贞苷G13的浓度,Kinetica 5.1软件计算药代动力学参数,GraphPad Prism 8.4.0软件进行数据分析。结果:红景天苷、木樨榄苷-11-甲酯、特女贞苷、毛蕊花糖苷、橄榄苦苷质量浓度在2.00~1385 ng·mL^(-1)范围内,女贞苷G13质量浓度在1.30~650 ng·mL^(-1)范围内线性关系良好,精密度RSD均<10%,提取回收率均在85%~105%,基质效应和稳定性均符合生物样品的要求。药动学研究结果显示,与生女贞子相比,酒女贞子的毛蕊花糖苷AUC_(0-∞)、MRT_(0-t)、t_(1/2)、C_(max)均显著升高(P<0.01),分别为751.36 ng·mL^(-1)·h,5.87 h,377.82 h,38.11 ng·mL^(-1);盐女贞子的特女贞苷和女贞苷G13 C_(max)、AUC_(0-∞)和t_(1/2)均显著升高(P<0.01),C_(max)分别为66.45、204.27 ng·mL^(-1),AUC_(0-∞)分别为342.69、423.44 ng·mL^(-1)·h,t_(1/2)分别为101.64、15.98 h;醋蒸、酒蒸、清蒸女贞子的橄榄苦苷C_(max)显著升高(P<0.05),分别为66.81、68.00、66.38 ng·mL^(-1)。醋女贞子的红景天苷和木樨榄苷-11-甲酯AUC_(0-∞)最高,分别为5782.74、545.26 ng·mL^(-1)·h。结论:本研究揭示了女贞子不同炮制品中6个活性成分在体内的变化规律及其差异特点,为女贞子不同炮制品的临床应用提供依据。Objective:To establish an UPLC-MS method for the analysis of salidroside,methyloleoside,specnuezhenide,acteoside,oleuropein,and G13 in plasma,and the differences in pharmacokinetic profiles of five different concoctions of Ligustri Lucidi Fructus,wine Ligustri Lucidi Fructus,vinegar Ligustri Lucidi Fructus,salt Ligustri Lucidi Fructus and steamed Ligustri Lucidi Fructus in vivo of rats were investigated.Methods:SPF-grade male SD rats were randomly divided into 6 groups,and were given 4.2 g·kg^(-1)of aqueous extracts of different concoctions of Ligustri Lucidi Fructus by gavage(for the amount of raw drug),and the plasma samples were methanol-precipitated proteins with geniposide as the internal standard,and the plasma samples were used to determine salidroside,methyloleoside,specnuezhenide,acteoside,oleuropein,and G13 in the plasma of the rats in the different time points by using the negative-ion SIM mode of UPLC-MS/MS.Kinetica 5.1 software was used to calculate the pharmacokinetic parameters,and GraphPad Prism 8.4.0 software was used to analyze the data.Results:The mass concentrations of salidroside,methyloleoside,specnuezhenide,acteoside and oleuropein were in the range of 2.00-1385 ng·mL^(-1),and the mass concentration of G13 was in the range of 1.30-650 ng·mL^(-1),with good linearity,the relative standard deviations of the precision were all less than 10%,the recoveries of the extracts were all in the range of 85%-105%,and the matrix effect and stability were in accordance with the requirements of biological samples.The results of pharmacokinetic study showed that the AUC_(0-∞),MRT_(0-t),t_(1/2),and C_(max)of acteoside were significantly higher in wine Ligustri Lucidi Fructus(P<0.01)compared to raw Ligustri Lucidi Fructus,which was 751.36 ng·mL^(-1)·h,5.87 h,377.82 h,and 38.11 ng·mL^(-1),respectively.C_(max),AUC_(0-∞),and t_(1/2)were significantly higher(P<0.01)for specnuezhenide and G13 in salt Ligustri Lucidi Fructus compared to raw Ligustri Lucidi Fructus,with C_(max)of specnuezhenide and G13 in

关 键 词：女贞子 红景天苷 木樨榄苷-11-甲酯 特女贞苷 毛蕊花糖苷 橄榄苦苷 女贞苷G13 炮制 超高效液相串联质谱 药代动力学 临床应用 

分 类 号：R917[医药卫生—药物分析学]