Development and validation of a sensitive and selective LC-MS/MS method for the determination of trans δ-veniferin, a resveratrol dehydrodimer, in rat plasma and its application to pharmacokinetics and bioavailability studies.

In this study, an accurate and reliable LC-MS/MS assay was firstly developed and validated for the quantitative determination of trans δ-veniferin (TVN) in rat plasma. Chlorzoxazone was used as the internal standard (IS). After one-step protein precipitation with methanol, the analyte and IS were separated on an ODS column by gradient elution with mobile phase of acetonitrile-0.2% formic acid at a flow rate of 0.3mL/min. Negative electrospray ionization was performed using multiple reactions monitoring (MRM) mode with transitions of m/z 453.0>410.9 for TVN, and m/z 168.0>132.0 for IS. Good linearity (R≥0.996) was observed over the concentration range of 5-5000ng/mL for TVN with a lower limit of quantification (LLOQ) of 5ng/mL. The mean recoveries for TVN and IS were 91.05% and 96.68%, respectively. The intra- and inter-day precisions (RSD) were no more than 10.5% and accuracies (RE) were within the range of -6.3% to 2.1%. The validated method was suitable for quantification of TVN and successfully applied to the pharmacokinetic study of TVN after oral and intravenous administration to rats. The oral absolute bioavailability of TVN was 14.2% in rat.