赛默飞色谱与质谱分析
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犬类血液中雷公藤甲素及其化合物MC002经LC–MS/MS同时测定以及在药代动力学研究中的应用

发布时间: 2014-05-07 09:34 来源:赛默飞色谱与质谱分析

  摘要:Ethnopharmacological relevance: Tripterygium wilfordii HOOK F(TWHF) is a traditional Chinese medicine used in the treatment of various autoimmune diseases and inflammatory disorders including rheumatoid arthritis(RA), systemic lupuseryth ematosus(SLE), and skin diseases. Triptolide(TP) is one of the main active ingredients of this traditional Chinese medicine. MC002 is a novel semi-synthetic derivate of TP which is highly water soluble, acts as a prodrug and is converted to TP in vivo. Aim of this study: A sensitive, rapid method for the simultaneous determination of TP and its chemo-unstable prodrug MC002 in dog blood was developed and validated using electrospray ionization(ESI) liquid chromatography–tandem mass spectrometry(LC–MS/MS). Using this method, a pharmacokinetic study of MC002 and TP following an intravenous drip infusion of 0.2mg/kg MC002 in dogs was performed. Materials and methods: Chemo-degradation of the prodrug in blood samples was inhibited by the addition of a small amount of sodium fluoride solution before using liquid–liquid extraction with ethyl acetate. The concentrations of MC002 and TP in dog blood were determined using the LC–MS/MS method. Results: The quantitative method showed good precision and stability and is suitable for the assay of biological samples. The pharmacokinetic study showed that the elimination of MC002 was faster than that of TP, and the concentrations and AUC0_t values of TP were higher than MC002. MC002 can rapidly convert to TP in vivo. Conclusions: This validated method was successfully applied in a pharmacokinetic study of MC002 following an intravenous drip infusion in dogs. With the development of this new prodrug of TP as a promising anti-cancer drug, this method is suitable for its further analysis in clinical studies.

网络链接http://www.sciencedirect.com/science/article/pii/S0378874113005722

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