title: Simultaneous quantification of trans-resveratrol and its sulfate and glucuronide metabolites in rat tissues by stable isotope-dilution UPLC-MS/MS analysis.
abstract: A rapid, sensitive, and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in the multiple reaction monitoring (MRM) mode has been developed and validated to investigate the distribution of trans-Resveratrol (Resv) and its metabolites in rats following intravenous (IV) administration at 20mg/kg body weight (BW). Resv and Resv metabolites were analyzed in the negative electrospray ionization mode and eluted with retention times of about 0.69-2.22min with a runtime of 7min. Stable deuterium-labeled Resv and its metabolites were used as the internal standards to correct for matrix effects and to allow for accurate quantification of Resv and its metabolites in a complex biological system. The method was validated with respect to linearity, within- and between-day precision, limit of quantification, recovery, and accuracy for all analytes. Upon examination at 0.5, 1, 2, and 4h post-administration, concentrations of Resv and its metabolites were the highest in the kidney, followed by plasma; specifically, the glucuronidated forms were the most abundant. In the liver and the brain, the predominant forms were the sulfated derivatives. In contrast, heart tissue contained the highest concentration of unmodified Resv at 0.5h post IV administration. The combined use of UPLC-MS/MS and isotope-dilution analysis, proved to be accurate and reliable in identifying and quantifying Resv and its various metabolites in biological samples at the nanomolar range. This technology is potentially applicable for other pharmacokinetic studies.
authors.affiliation: Chemistry Division, Center for Education, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan, ROC. Electronic address: blou@mail.cgu.edu.tw.
authors.forename: Bih-Show
authors.initials: BS
authors.lastname: Lou
authors.affiliation: Chemistry Division, Center for Education, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan, ROC.
authors.forename: Pei-Shan
authors.initials: PS
authors.lastname: Wu
authors.affiliation: Department of Physiology, College of Medicine, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan, ROC.
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Hou
authors.affiliation: Department of Physiology, College of Medicine, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan, ROC.
authors.forename: Fu-Yin
authors.initials: FY
authors.lastname: Cheng
authors.affiliation: Department of Physiology, College of Medicine, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan, ROC. Electronic address: jkc508@mail.cgu.edu.tw.
authors.forename: Jan-Kan
authors.initials: JK
authors.lastname: Chen
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D020719:Glucuronides / Q000737:chemistry*; D007554:Isotopes / Q000737:chemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry*; D013431:Sulfates / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D020719:Glucuronides; D007554:Isotopes; D013267:Stilbenes; D013431:Sulfates; D000077185:Resveratrol
keywords: 3-O-d-glucuronidated conjugate; 3-O-sulfated conjugate; Isotope-dilution; Resveratrol; UPLC–MS/MS