化学
色谱法
蛋白质沉淀
代谢物
电喷雾电离
药代动力学
选择性反应监测
质谱法
串联质谱法
苷元
分析物
葡萄糖醛酸
液相色谱-质谱法
糖苷
药理学
立体化学
生物化学
医学
作者
Lu Wang,Haifeng Shen,Yang Zhan,Yifan Zhang,Yong Zhang,Min Chen,Xiaoju Li,Dafang Zhong
标识
DOI:10.1016/j.jpba.2022.115203
摘要
Hyperlipidemia is a disease characterized by abnormal blood lipid levels and is the leading risk factor for cardiovascular disease. 3′,4′-Dimethoxy flavonol-3-O-glucoside (abbreviated DF3G) is a new lipid-lowering drug created as a flavonoid structural analog. The principal metabolite of DF3G in human plasma is the aglycone glucuronide conjugate M2. The purpose of this study is to use liquid chromatography-tandem mass spectrometry to develop and validate a quantitative analysis method for DF3G and its metabolite M2 in human plasma, and to use the method to investigate the pharmacokinetics of DF3G and M2 in a clinical trial. This method employed DF3G-d6 as the internal standard, and plasma samples were processed by protein precipitation. Isocratic separation could accurately differentiate DF3G, M2, and DF3G-d6 from endogenous components in the matrix or other components in the samples, and endogenous components in the matrix had little impact on ionization efficiency. Positive electrospray ionization with multiple reaction monitoring (MRM) transitions of m/z 461.2 → 299.0 for DF3G, m/z 475.1 → 299.1 for M2 and m/z 467.1 → 305.1 for DF3G-d6 was used for quantification. The DF3G and M2 linear range for plasma were in the range of 4.00/4.00 ng/mL to 4000/4000 ng/mL. Both the analytes and the internal standard were stable regardless of whether they were in solution or plasma samples. The accuracy of the average concentration of the quality control samples was within 15% of the theoretical value, and the RSD was less than 15%. The method is rapid, accurate, straightforward, and precise. It is appropriate for the determination of DF3G and M2 concentrations in human plasma and has been successfully applied to determine the pharmacokinetic analysis in phase I clinical trials.
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