Determination of the retinoic acid metabolism blocking agent R115866 in human plasma by gas chromatography-high resolution mass spectrometry

A sensitive GC-MS method was developed for the determination of a new retinoic acid metabolism blocking agent R115866 in human plasma samples. A deuterium labeled internal standard (i.s.) was used. Sample preparation consisted of a one step liquid-liquid extraction, followed by derivatisation with pentafluorobenzylbromide and a clean-up step. The linearity, extraction recovery, accuracy and precision of the method were tested, as well as the stability of the compound. The calibration range was from 0.01 to 10 ng mL⁻¹ and the LLOQ was 0.01 ng mL⁻¹. The method was successfully applied for the determination of unchanged R115866 plasma levels after oral dosing in healthy volunteers.