Simultaneous determination of roflumilast and its metabolite in human plasma by LC-MS/MS: Application for a pharmacokinetic study.

Roflumilast had shown good efficacy and safety in Caucasian COPD patients after oral administration of 0.5mg. The main active metabolite of it is roflumilast N-oxide. A reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantitation method was developed for the simultaneous determination of them in human plasma with rather low limits of quantitation for roflumilast (0.02ng/mL) and roflumilast N-oxide (0.04ng/mL). Human plasma samples were prepared by solid phase extraction (SPE), which ensured high recovery and slight matrix effect for the both analytes. This method showed good linearity, accuracy, precision and stability in the range of 0.02-10ng/mL and 0.04-50ng/mL for roflumilast and roflumilast N-oxide respectively. The developed method was successfully applied for the pharmacokinetic research in Chinese healthy volunteers after oral administration of 0.25mg, 0.375mg and 0.5mg of roflumilast tablet.