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

doi:10.4155/bio.13.350

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 journal › Article › peer-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 language	English
Pages (from-to)	919-33
Number of pages	15
Journal	Bioanalysis
Volume	6
Issue number	7
DOIs	https://doi.org/10.4155/bio.13.350
Publication status	Published - Apr 2014

Keywords / Materials (for Non-textual outputs)

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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10.4155/bio.13.350

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@article{3d88bf96a93d4606832e55c1a04651a4,

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

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

author = "Rodrigues, {Alison V M} and Maggs, {James L} and McWilliam, {Stephen J} and Munir Pirmohamed and Muireann Coen and Wilson, {Ian D} and Park, {B Kevin} and Antoine, {Daniel J}",

year = "2014",

month = apr,

doi = "10.4155/bio.13.350",

language = "English",

volume = "6",

pages = "919--33",

journal = "Bioanalysis",

issn = "1757-6180",

publisher = "Future Science",

number = "7",

}

TY - JOUR

T1 - Quantification of urinary mevalonic acid as a biomarker of HMG-CoA reductase activity by a novel translational LC-MS/MS method

AU - Rodrigues, Alison V M

AU - Maggs, James L

AU - McWilliam, Stephen J

AU - Pirmohamed, Munir

AU - Coen, Muireann

AU - Wilson, Ian D

AU - Park, B Kevin

AU - Antoine, Daniel J

PY - 2014/4

Y1 - 2014/4

N2 - 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.

AB - 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.

KW - Biomarkers

KW - Calibration

KW - Chromatography, Reverse-Phase

KW - Humans

KW - Hydroxymethylglutaryl CoA Reductases

KW - Mevalonic Acid

KW - Tandem Mass Spectrometry

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.4155/bio.13.350

DO - 10.4155/bio.13.350

M3 - Article

C2 - 24806902

SN - 1757-6180

VL - 6

SP - 919

EP - 933

JO - Bioanalysis

JF - Bioanalysis

IS - 7

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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