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.
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.
Authors: Peter Lundbäck; Pernilla Stridh; Lena Klevenvall; Rosalind E Jenkins; Marie Fischer; Erik Sundberg; Ulf Andersson; Daniel J Antoine; Helena Erlandsson Harris Journal: Antioxid Redox Signal Date: 2015-02-06 Impact factor: 8.401