title: 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.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, Korea.
authors.forename: Min Gi
authors.initials: MG
authors.lastname: Kim
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.forename: Yohan
authors.initials: Y
authors.lastname: Choi
authors.forename: Jae Kuk
authors.initials: JK
authors.lastname: Ryu
authors.forename: Seung Woo
authors.initials: SW
authors.lastname: Shin
authors.forename: Hyun Wook
authors.initials: HW
authors.lastname: Choo
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Yoo
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002211:Capsaicin / Q000031:analogs & derivatives / Q000097:blood; D002396:Catechols / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005233:Fatty Alcohols / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D016018:Least-Squares Analysis; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D002396:Catechols; D005233:Fatty Alcohols; C007845:gingerol; D002211:Capsaicin; C040937:nonivamide