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.

6-Gingerdiols as the Major Metabolites of 6-Gingerol in Cancer Cells and in Mice and Their Cytotoxic Effects on Human Cancer Cells

“…The pharmacokinetics of 6-gingerol in mice, rats, and humans have been examined by different research groups. − However, the metabolic fate of 6-gingerol, especially in cancer cells and in mice, is still unclear. Nakazawa and co-workers orally administrated 6-gingerol to rats and found that it could be converted to one major metabolite, 6-gingerol-4′-O-β-glucuronide, in bile and six other minor metabolites in urine .…”

Formulation of Phytosomes with Extracts of Ginger Rhizomes and Rosehips with Improved Bioavailability, Antioxidant and Anti-Inflammatory Effects In Vivo

“…injection), and blood was collected by cardiac puncture in EDTA-containing tubes. The resulting blood samples (n = 3 animals/time point) were kept on ice, and the plasma obtained by centrifugation at 2000× g was stored at -80 • C until the evaluation of the free 6-gingerol levels was conducted using a method adapted from [33] as described below at the Section "Samples preparation for measurement of free 6-gingerol".…”

“…Accurately weighted tissue samples (<200 mg) were homogenized in 200 µL of saline buffer on ice. After this, 10 µL of internal standard (IS) nonivamide 5 µg/mL in acetonitrile and 790 µL of acetonitrile or 390 µL of acetonitrile for 100 µL of plasma were added to each sample (homogenized tissue or plasma) [33]. The samples were vigorously vortexed and centrifuged at 13,500× g for 15 min.…”

Integrated LC-MS/MS Analytical Systems and Physical Inspection for the Analysis of a Botanical Herbal Preparation

“…Gingerol is the major pungent, nonvolatile, phenolic component of ginger. The herb Zingiber officinale is used to disperse bio-energy Qi , keep Qi in motion and assist in regulating blood circulation; this is the reason for the interdependence between Yin and Yan g [9]. Previous studies have revealed that Ziziphus jujube contains various constituents including triterpenic acids, phenolic acids, and polysaccharides, which may also possess bioactivity [10].…”