SummaryA 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 75-300 ng mL 1 and for application of the method to a clinical studywith the drug rosuvastatin.
Background: The amount of method development and assay validation required to support analysis of solutions from in vitro systems is a consideration of analytical laboratories performing this type of analysis. As there is little information from regulatory bodies as to how much assay development and validation is required, analytical laboratories need to decide on the best approach for this type of work. In this paper, we describe an efficient ‘fit-for-purpose’ approach that has been developed to support buffer sample analysis from Safety Pharmacology hERG studies. Results: Method development has been minimized with the aid of compound modeling software and generic HPLC–MS/MS analytical systems. The assay is evaluated prior to sample analysis using simple qualification procedures to support ‘one-off’ analyses. Conclusion: The result is an efficient process that allows speedy and confident analysis of in vitro samples to successfully support regulatory hERG in vitro studies without the additional workload of a full validation procedure.
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