Quantification of Urinary Mevalonic Acid as a Biomarker of HMG-CoA Reductase Activity by a Novel Translational LC-MS/MS Method



Rodrigues, Alison VM, Maggs, James L, McWilliam, Stephen J ORCID: 0000-0002-0509-7425, Pirmohamed, Munir ORCID: 0000-0002-7534-7266, Coen, Muireann, Wilson, Ian D ORCID: 0000-0002-8558-7394, Park, B Kevin ORCID: 0000-0001-8384-824X and Antoine, Daniel J
(2014) Quantification of Urinary Mevalonic Acid as a Biomarker of HMG-CoA Reductase Activity by a Novel Translational LC-MS/MS Method. Bioanalysis, 6 (7). pp. 919-933.

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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.

Item Type: Article
Additional Information: Export Date: 11 June 2014## TULIP Type: Articles/Papers (Journal) ##
Uncontrolled Keywords: Humans, Mevalonic Acid, Hydroxymethylglutaryl CoA Reductases, Calibration, Tandem Mass Spectrometry, Chromatography, Reverse-Phase, Biomarkers
Depositing User: Symplectic Admin
Date Deposited: 24 Mar 2017 14:31
Last Modified: 19 Jan 2023 07:08
DOI: 10.4155/bio.13.350
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3006625