An inter-laboratory cross-validation study for the determination of perampanel in human plasma by liquid chromatography assays.

Abstract

For sample assay to support global clinical studies of perampanel, a novel AMPA receptor antagonist, six chromatographic assay methods in human plasma were developed and fully validated at each laboratory using liquid chromatography with tandem mass spectrometry (LC-MS/MS) or LC with fluorescence detection (LC-FL). In this study, samples fortified with known perampanel concentrations were assayed at six laboratories to find whether assay data are comparable. Perampanel was extracted by protein precipitation or liquid-liquid extraction, chromatographed on a reverse-phase column then detected by MS/MS or FL to achieve the limit of quantification of 0.25 or 1 ng/mL. Cross-validation samples at four concentrations prepared at a central laboratory were determined at six laboratories and the mean accuracy at each concentration was within ±15% except the low concentration at one laboratory (relative error -17.4%), suggesting that plasma concentrations of perampanel in clinical trials can be compared across laboratories.