Rapid, Sensitive and Selective Analysis of trans-Resveratrol in Rat Plasma by LC–MS–MS

Abstract

A rapid, sensitive and highly selective liquid chromatography/tandem mass spectrometry (LC–MS–MS) using an atmospheric pressure chemical ionization (APCI) method was developed to determine the concentration of trans-resveratrol in rat plasma. Samples were extracted using ethyl acetate after daidzein was added as an internal standard (IS). The main advantages of this method were the high sensitivity (a lower limit of quantification, LLOQ, of 0.1 ng mL⁻¹) and the short analysis time (total run time 3.2 min per sample). Separation was performed on a ZORBAX ODS column with a mobile phase that consisted of acetonitrile/water (48:52, v/v). trans-Resveratrol and IS were detected using a triple-quadrupole mass spectrometer in the selective reaction monitoring (SRM) mode with the parent-to-product quantifier transitions [M–H]⁻ m/z 226.8 → 142.9 and [M–H]⁻ m/z 252.9 → 252.9 for trans-resveratrol and IS, respectively. The method was confirmed to be accurate and precise with a linearity range of 0.1–500 ng mL⁻¹ with r > 0.99. Recoveries for trans-resveratrol and IS were within 90–101%. The accuracy and precision for the assay were determined by calculating the intra- and inter-batch variation for quality control (QC) samples at four concentration levels with a relative standard deviation (RSD) of <15%. This method was successfully applied to determine trans-resveratrol in rat plasma and proved suitable for pharmacokinetic study after intragastric administration of trans-resveratrol in sustained release granules and normal granules, respectively.