Quantitation of plasma mevalonic acid using gas chromatography-electron capture mass spectrometry

Circulating concentrations of mevalonic acid (MVA) change in parallel with, and may be used as a marker of cholesterol biosynthesis. Plasma MVA levels have been quantified using a sensitive and specific capillary gas chromatography-electron capture mass spectrometric assay. The detection limit for MVA in plasma is 100 pg/ml; the intra-assay variation is 5.11%; the inter-assay variation is 7.7%. Using this assay, the mean plasma MVA in 15 normolipidemic subjects was 2.37 +/- 1.2 ng/ml (range 0.41-5.31 ng/ml). Administration of 40 mg of simvastatin (an HMG-CoA reductase inhibitor) significantly accenutated the diurnal decrease in plasma MVA levels. This assay may be useful in investigating cholesterol synthesis rates in different dyslipidemias and individual responses of HMG-CoA reductase-inhibiting drugs.