UPLC-MS/MS quantification of quercetin in plasma and urine following parenteral administration
Tóm tắt
Study of pharmacokinetics of quercetin (Qu) and its derivatives after infusion is required in order to better understand mechanisms of therapeutic action of the formulation and development the strategic approaches to treat the underlying disease and pathologically similar syndromes. A pharmacokinetic study of Qu products is a complex analytical problem. We developed and validated a new method for quantification of Qu and its metabolites in human plasma and urine following intravenous administration of Qu formulation. The method is based on the solid-phase extraction with the help of Oasis® HLB cartridges and ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) quantification. The calibration curves plotted for concentration range of 25–3000 ng/ml for Qu and isorhamnetin in blood plasma and of 100–8000 ng/ml for the same substances in urine were best described by a quadratic function. Qu conjugates underwent preliminary hydrolysis by the mixture of enzymes of sulphatase and β-glucuronidase. The antioxidant L-cysteine mixed with ascorbic acid was used for stabilization of Qu and its metabolites during handling of samples and chromatographic runs with mass detection. The method validation as well as the stability study results confirmed that the developed method meets the established requirements (selectivity, lower limit of quantification, accuracy, precision, recovery). The main pharmacokinetic parameters of Qu and its metabolites were determined in blood plasma and urine after intravenous administration of Corvitin® (parenteral formulation combining Qu and polyvinylpyrrolidone at a ratio of 1:9) in 12 healthy volunteers. We showed that the method development for Qu quantification in biological matrixes is valuable and reliable.
Tài liệu tham khảo
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