Characterization of [6]-gingerol metabolism in rat by liquid chromatography electrospray tandem mass spectrometry

Abstract

[6]-Gingerol is a structural analog of capsaicin, an agonist of the transient receptor potential channel vanilloid 1, which is known to have therapeutic properties for the treatment of pain and inflammation. A selective and sensitive quantitative method for the determination of [6]-gingerol by HPLC-ESI/MS/MS was developed. The method consisted of a protein precipitation extraction followed by analysis using liquid chromatography electrospray tandem mass spectrometry. The chromatographic separation was achieved using a Thermo 100 × 2.1 mm C(8) column combined with an isocratic mobile phase composed of acetonitrile, water and formic acid (80:20:0.1) at a flow rate of 250 μL/min. The mass spectrometer was operating in SRM mode and an analytical range set at 20-5000 ng/mL was used to construct a calibration curve in rat plasma. The interbatch precision (%CV) and accuracy (%NOM) observed were 2.9-10.8% and 98.1-102.1% in rat plasma. Similarly, precision and accuracy in rat liver microsomal suspension were also evaluated at nominal concentrations of 1, 25 and 100 μm; the precision (%CV) was <3.4% and the accuracy (%NOM) observed ranged from 89.7 to 109.4%. An in vitro metabolic stability study using rat liver microsomes was performed to determine intrinsic clearance of [6]-gingerol. The results show slow degradation with a T(1/2) of 163 min and relatively low intrinsic clearance suggesting that phase I metabolism may not be a major contributor of the drug clearance. Further analyses were performed to characterize in vitro and in vivo metabolites. Three main phase I metabolites and four phase II metabolites were identified by HPLC-MS/MS and HPLC-MSD TOF. However, the results suggest that glucuronidation of hydroxylated [6]-gingerol is the primary metabolite excreted in rat urine.

Intrathecal [6]‐Gingerol Administration Alleviates Peripherally induced Neuropathic Pain in Male Sprague–Dawley Rats

“…All samples were kept at −80 °C pending analysis. The analysis of [6]‐gingerol in rat plasma was performed as previously described (Gauthier et al ., ). Pharmacokinetic parameters (AUC, λ z and T 1/2 ) were calculated using a non‐compartmental approach.…”

Gingerols and shogaols: Important nutraceutical principles from ginger

“…6-Gingerol-glucuronide was identified as the major metabolite of 6-GN following b-glucuronidase hydrolysation. A quantitative LC-MS/MS for the determination of 6-GN in rat tissues was developed and validated by Gauthier et al (2011). They proposed that phase I metabolism may not be a major contributor to GN clearance from the liver, owing to its slow degradation (163 min half-life).…”

Dietary Agonists of TRPV1 Inhibit Gastric Acid Secretion in Mice

“…Although 6-gingerol was reported to exhibit lower potency than capsaicin in the activation of TRPV1 in vitro [5], the present results suggested that capsaicin has lower potency than 6-gingerol in in vivo experiments. Previous reports showed that 6-gingerol has relatively high metabolic stability based on the degradation kinetics [26,27]. Therefore, the present results were thought to show that 6-gingerol even at half the dose (≧ 15 mg/kg, p.…”