Determination and pharmacokinetics of [6]‐gingerol in mouse plasma by liquid chromatography–tandem mass spectrometry

Abstract

This study describes the development of a rapid and sensitive high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS) assay for the quantification of [6]-gingerol in mouse plasma and application to a pharmacokinetic study after dose ranging in mice. The assay involved a protein precipitation step with acetonitrile and an isocratic elution using a mobile phase consisting of acetonitrile and water containing 0.1% formic acid (80:20 v/v). The multiple reaction monitoring was based on the transition of m/z = 277.2 → 177.1 for [6]-gingerol and 294.2 → 137.1 for nonivamide (internal standard). The assay was validated to demonstrate the specificity, linearity, recovery, accuracy, precision and stability. The calibration curves were linear over the wide concentration range of 10-10,000 ng/mL (r ≥ 0.9988). The lower limit of quantification was 10 ng/mL using a small volume of mouse plasma (20 μL). The method was successfully applied to a pharmacokinetic study in mice after intravenous injection of [6]-gingerol at 1.5, 3 and 6 mg/kg doses. The pharmacokinetics of [6]-gingerol were linear over the dose range studied as demonstrated by the linear increase in area under the concentration-time curve (AUC(inf)) with no significant change in the systemic clearance (Cl(s)), volume of distribution (V(ss)) and elimination half-life (t(1/2)) as a function of dose.