Quantitation and metabolism of mitoquinone, a mitochondria-targeted antioxidant, in rat by liquid chromatography/tandem mass spectrometry.

Abstract

Mitoquinone (MitoQ10 mesylate) is a mitochondria-targeted antioxidant undergoing development for the treatment of neurodegenerative diseases. The aim of this study was to develop and validate an assay based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) to determine mitoquinone and to detect and identify the metabolites of MitoQ10 in rat plasma after an oral dose. After a simple protein precipitation step, plasma samples were analyzed by reversed-phase liquid chromatography using gradient elution with acetonitrile/water/formic acid. Electrospray ionization in the positive ion mode with multiple reaction monitoring (MRM) was used to analyze mitoquinone employing the deuterated compound (d3-MitoQ10 mesylate) as internal standard. The calibration curve for mitoquinone was linear over the concentration range 0.5-250 ng/mL with a correlation coefficient>0.995. The method was sensitive (limit of quantitation 0.5 ng/mL) and had acceptable accuracy (relative error<8.7%) and precision (intra- and inter-day coefficient of variation<12.4%). Recoveries of mitoquinone at concentrations of 1.5, 20 and 200 ng/mL were in the range 87-114%. The method was successfully applied to a pharmacokinetic study in rat after a single oral dose in which four metabolites of MitoQ10 were tentatively identified as hydroxylated MitoQ10, desmethyl MitoQ10 and the glucuronide and sulfate conjugates of the quinol form of MitoQ10.

• Authors: Yan Li, Hu Zhang, J Paul Fawcett, Ian G Tucker
• Journal: Rapid communications in mass spectrometry : RCM (Rapid Commun Mass Spectrom) Vol. 21 Issue 13 Pg. 1958-64 ( 2007) ISSN: 0951-4198 [Print] England
• PMID: 17534852 (Publication Type: Journal Article)
• Copyright: Copyright (c) 2007 John Wiley & Sons, Ltd.

Chemical References

• Antioxidants
• Organophosphorus Compounds
• Ubiquinone
• mitoquinone

Topics

• Animals
• Antioxidants (chemistry, metabolism, pharmacokinetics, pharmacology)
• Calibration
• Chromatography, Liquid (methods)
• Male
• Mitochondria (drug effects)
• Molecular Structure
• Organophosphorus Compounds (blood, chemistry, pharmacokinetics, pharmacology)
• Rats
• Rats, Wistar
• Reference Standards
• Reproducibility of Results
• Sensitivity and Specificity
• Specific Pathogen-Free Organisms
• Tandem Mass Spectrometry (methods)
• Ubiquinone (blood, chemistry, pharmacokinetics, pharmacology)