Quantification of urinary mevalonic acid as a biomarker of HMG-CoA reductase activity by a novel translational LC-MS/MS method

Alison V M Rodrigues, James L Maggs, Stephen J McWilliam, Munir Pirmohamed, Muireann Coen, Ian D Wilson, B Kevin Park, Daniel J Antoine

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Mevalonic acid (MVA), as a product of 3-hydroxy-3-methylglutaryl coenzyme A reductase, represents a potential multipurpose biomarker in health and disease. A translational urinary MVA quantification method was developed, validated and used to demonstrate the diurnal variation of urinary MVA excretion in rats and healthy children.

METHODS: Urinary MVA was converted to mevalonolactone at pH 2, extracted with ethyl acetate and quantified by reversed-phase liquid chromatography-tandem mass spectrometry.

RESULTS: The assay had a dynamic range of 0.0156-10 µg/ml with precision <15% CV, accuracy 85-115% and was transferred between laboratories. Urinary MVA excretion in rats and healthy children displayed a diurnal variation consistent with the known diurnal variation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity.

CONCLUSION: Urinary MVA can be quantified accurately over a wide dynamic range by a validated translational and transferable method with biomarker capability.

Original languageEnglish
Pages (from-to)919-33
Number of pages15
JournalBioanalysis
Volume6
Issue number7
DOIs
Publication statusPublished - Apr 2014

Keywords

  • Biomarkers
  • Calibration
  • Chromatography, Reverse-Phase
  • Humans
  • Hydroxymethylglutaryl CoA Reductases
  • Mevalonic Acid
  • Tandem Mass Spectrometry
  • Journal Article
  • Research Support, Non-U.S. Gov't

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