title: Quantification of pinosylvin in rat plasma by liquid chromatography-tandem mass spectrometry: application to a pre-clinical pharmacokinetic study.
abstract: Pinosylvin (trans-3,5-dihydroxystilbene), a naturally occurring analogue of resveratrol (trans-3,5,4'-trihydoxystilbene), exhibited various beneficial pharmacological activities in pre-clinical studies. To further probe its potential medicinal application, a sensitive liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was developed and validated for the quantification of pinosylvin in rat plasma. A simple protein precipitation procedure was used for plasma cleanup before analysis by LC-MS/MS with electrospray ionisation and multiple reaction monitoring in its negative ion mode. This LC-MS/MS method demonstrated good selectivity, accuracy (intra- and inter-day analytical recovery within 100±7.7%), precision (intra- and inter-day coefficient of variation<12.0%) and sensitivity (lower limit of detection=1.0ng/mL), with excellent linearity (R(2)>0.99) over the range of 1-1000ng/mL. The pharmacokinetic profiles of pinosylvin were subsequently assessed in Sprague-Dawley rats. Following intravenous administration (5 or 10mg/kg), plasma levels of pinosylvin declined rapidly with a short half-life (t1/2<10min). Upon oral administration at 15mg/kg, pinosylvin could not be quantified in plasma (<1ng/mL) while dose-escalation to 50mg/kg led to a low and erratic plasma exposure with very poor estimated oral bioavailability (F<1%). The short half-life and limited systemic exposure of pinosylvin prompt caution in its therapeutic application and it warrants exploration in developing pinosylvin pro-drug.
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260, Singapore.
authors.forename: Samuel Chao Ming
authors.initials: SC
authors.lastname: Yeo
authors.forename: Wenxia
authors.initials: W
authors.lastname: Luo
authors.forename: Jinzhu
authors.initials: J
authors.lastname: Wu
authors.forename: Paul C
authors.initials: PC
authors.lastname: Ho
authors.forename: Hai-Shu
authors.initials: HS
authors.lastname: Lin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002853:Chromatography, Liquid / Q000379:methods*; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013267:Stilbenes / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000094162:Phytoalexins
chemical_list: D013267:Stilbenes; C049032:pinosylvin; D000094162:Phytoalexins