基于UPLC-QTOF/MS的中药金花清感颗粒体外及入血成分鉴定和初步药动学特征分析

Identification of components in vitro and plasma of Jinhua Qinggan granules and preliminary pharmacokinetics analysis

金花清感颗粒(Jinhua Qinggan granules,JHQG)是中药抗新冠肺炎"三药三方"之一,具有明确的临床疗效。金花清感颗粒药味众多、成分复杂,目前尚无系统的体内外化学成分研究报道。本研究建立了一种超高效液相色谱-四级杆飞行时间质谱(UPLC-QTOF/MS)联用方法鉴别抗新冠肺炎中药金花清感颗粒的化学成分,采集并分析大鼠给药后的血浆样品,探究灌胃给药8 h内大鼠体内暴露成分,并在此基础上进行初步的药物动力学(pharmacokinetics,PK)分析。通过UPLC-QTOF/MS分析和对照品验证,共鉴别出金花清感颗粒组方中77种化学成分,其中22个化合物为体内暴露组分,主要来源于金银花、黄芩、连翘三种药材;利用房室模型评估大鼠6个时间点血药浓度,获得4种体内高暴露化学成分的8项PK参数,简要阐明了金花清感颗粒体内主要暴露组分的代谢特征。该方法简便高效,灵敏准确,为金花清感颗粒药效物质基础与作用机制的阐明提供了依据,对传统中医药组方在抗击新冠病毒中的基础与应用研究具有一定参考意义。

As one of the"Three Drugs Three Prescriptions"anti-COVID-19 traditional Chinese medicine,Jinhua Qinggan granules(JHQG)has been proved to have clear clinical effects.With complex medicinal flavors and ingredients,there is no systematic research report on chemical composition in vivo or in vitro.An ultrahigh pressure liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-QTOF/MS)method was developed in this study to identify the components of the anti-COVID-19 traditional Chinese medicine JHQG granules.Analyze the collected rat plasma samples after administration and explore the exposed components in rats within 8 hours after intragastric administration.Preliminary pharmacokinetic analysis was then performed on this basis.Through UPLC-QTOF/MS analysis and verification by standard products,a total of 77 chemical components in JHQG formula have been identified,among which 22 compounds were highly exposed in vivo,mainly derived from three medicinal materials of honeysuckle,scutellaria and forsythia.Through the assessment of the blood drug concentration by the compartment model,6 PK parameters of 4 high-exposure chemical components have been obtained,clarifying the metabolic characteristics of the main exposed components in JHQG briefly.The method is simple,efficient,sensitive and accurate and provides research basis to the clarification of the pharmacodynamics material basis and mechanism of JHQG,which has certain reference significance for the basics and applications research of the traditional Chinese medicine prescriptions in fighting the SARS-CoV-2.