Development of a sensitive assay for the determination of mevalonic acid in urine and its application to clinical studies with rosuvastatin

A simple method is described for the analysis of mevalonic acid (MVA) in human urine involving conversion to MVA lactone (MVAL) and determination by GC-MS. A strategy is described to achieve a low limit of quantitation to overcome the constraint that calibration must be performed in urine (since MVAL is adsorbed in the absence of matrix) and control urine always contains significant amounts of MVA. Data are presented for validation of the method over the range 7.5–300 ng mL−1 and for application of the method to a clinical study with the drug rosuvastatin.