title: Quantification of urinary mevalonic acid as a biomarker of HMG-CoA reductase activity by a novel translational LC-MS/MS method.
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.
  
  
  CONCLUSIONS
  Urinary MVA can be quantified accurately over a wide dynamic range by a validated translational and transferable method with biomarker capability.
authors.affiliation: >MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, L69 3GE, UK.
authors.forename: Alison V M
authors.initials: AV
authors.lastname: Rodrigues
authors.forename: James L
authors.initials: JL
authors.lastname: Maggs
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: McWilliam
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
authors.forename: Muireann
authors.initials: M
authors.lastname: Coen
authors.forename: Ian D
authors.initials: ID
authors.lastname: Wilson
authors.forename: B Kevin
authors.initials: BK
authors.lastname: Park
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Antoine
mesh_terms: D015415:Biomarkers / Q000652:urine*; D002138:Calibration; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D008798:Mevalonic Acid / Q000652:urine*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D015415:Biomarkers; D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid