Analytical method development for synthesized conjugated metabolites of trans-resveratrol, and application to pharmacokinetic studies
2012
Iwuchukwu, Otito F. | Sharan, Satish | Canney, Daniel J. | Nagar, Swati
Trans-3,5,4′-trihydroxystilbene (trans-resveratrol, RES) exhibits very low bioavailability due to extensive conjugative metabolism. Whether RES metabolites exhibit pharmacologic activity is of great interest. The present study aimed at synthesis of monoconjugates of RES – the 3- and 4′ monosulfates (R3S and R4′S), and the 3- and 4′ monoglucuronides (R3G and R4′G). Synthesis, purification, and yield are described. Synthesized metabolites were utilized to develop a sensitive LC–MSⁿ assay for direct quantitation of all analytes. The assay was validated for intra- and inter-day precision and accuracy. Synthesis of RES conjugates and development and validation of a sensitive bioanalytical assay were applied to pharmacokinetic evaluation of RES and its circulating monoconjugates in C57BL mice. The study is a first report of direct quantitation of RES monosulfates and monoglucuronides. These results will aid in characterizing the disposition of RES and its major or active metabolites in vivo.
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