An LC-MS/MS procedure for the quantification of naproxen in human plasma: development, validation, comparison with other methods, and application to a pharmacokinetic study.

A sensitive, precise and accurate quantitative LC-MS/MS method for the measurement of naproxen in human plasma was developed and completely validated according to current FDA and EMA guidelines. The new method employs acetonitrile protein precipitation for sample preparation and uses ketoprofen as the internal standard. Suitability of the new assay was assessed in comparison with 36 reported bioanalytical assays and the pharmacokinetic results obtained by the new method were compared to 11 reported studies in humans. The principal advantage of this LC-MS/MS method is the simultaneous achievement of high absolute recovery (90.0±3.6%), acceptable sensitivity (lower limit of quantitation of 0.100 μg/mL), high inter-day precision (CV≤9.4%), high analytical recovery (between 94.4 and 103.1%), and excellent linearity over the concentration range 0.100-50.0 μg/mL (r(2)≥0.998) combined with a short run time of only 2 min.