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J Pharm Biomed Anal. 2012 Apr 7;63:1-8. doi: 10.1016/j.jpba.2011.12.006. Epub 2011 Dec 16.

Analytical method development for synthesized conjugated metabolites of trans-resveratrol, and application to pharmacokinetic studies.

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Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA.


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-MS(n) 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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