采用新型转化型液相色谱-串联质谱法对尿中甲羟戊酸进行定量分析，作为HMG-CoA还原酶活性的生物标志物。
Quantification of urinary mevalonic acid as a biomarker of HMG-CoA reductase activity by a novel translational LC-MS/MS method.
作者信息
Rodrigues Alison V M, Maggs James L, McWilliam Stephen J, Pirmohamed Munir, Coen Muireann, Wilson Ian D, Park B Kevin, Antoine Daniel J
机构信息
>MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, L69 3GE, UK.
出版信息
Bioanalysis. 2014 Apr;6(7):919-33. doi: 10.4155/bio.13.350.
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.
背景
甲羟戊酸（MVA）作为3-羟基-3-甲基戊二酰辅酶A还原酶的产物，是一种在健康和疾病方面具有潜在多用途的生物标志物。我们开发、验证了一种可转化的尿MVA定量方法，并用于证明大鼠和健康儿童尿MVA排泄的昼夜变化。
方法
尿MVA在pH 2条件下转化为甲羟戊酸内酯，用乙酸乙酯萃取，并用反相液相色谱-串联质谱法定量。
结果
该测定法的动态范围为0.0156-10μg/ml，精密度<15%CV，准确度为85-115%，并可在不同实验室间转移。大鼠和健康儿童的尿MVA排泄呈现出昼夜变化，与已知的肝脏3-羟基-3-甲基戊二酰辅酶A还原酶活性的昼夜变化一致。
结论
通过一种经过验证的具有生物标志物能力的可转化且可转移的方法，可在很宽的动态范围内准确量化尿MVA。
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