TY - JOUR
T1 - Simultaneous quantification of trans-resveratrol and its sulfate and glucuronide metabolites in rat tissues by stable isotope-dilution UPLC-MS/MS analysis
AU - Lou, Bih Show
AU - Wu, Pei Shan
AU - Hou, Chun Wei
AU - Cheng, Fu yin
AU - Chen, Jan Kan
PY - 2014/6
Y1 - 2014/6
N2 - 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 20. mg/kg body weight (BW). Resv and Resv metabolites were analyzed in the negative electrospray ionization mode and eluted with retention times of about 0.69-2.22. min with a runtime of 7. min. 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 4. h 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 0.5. h 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.
AB - 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 20. mg/kg body weight (BW). Resv and Resv metabolites were analyzed in the negative electrospray ionization mode and eluted with retention times of about 0.69-2.22. min with a runtime of 7. min. 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 4. h 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 0.5. h 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.
KW - 3-O-d-glucuronidated conjugate
KW - 3-O-sulfated conjugate
KW - Isotope-dilution
KW - Resveratrol
KW - UPLC-MS/MS
UR - https://www.scopus.com/pages/publications/84894232455
U2 - 10.1016/j.jpba.2014.01.039
DO - 10.1016/j.jpba.2014.01.039
M3 - 文章
C2 - 24561334
AN - SCOPUS:84894232455
SN - 0731-7085
VL - 94
SP - 99
EP - 105
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
ER -