Simultaneous quantification of atomoxetine as well as its primary oxidative and O-glucuronide metabolites in human plasma and urine using liquid chromatography tandem mass spectrometry (LC/MS/MS)

A sensitive and selective liquid chromatography tandem mass spectrometry (LC/MS/MS) method for the determination of atomoxetine and its metabolites (4-hydroxyatomoxetine, N- des-methylatomoxetine, and 4-hydroxyatomoxetine- O-glucuronide) has been developed for human plasma and urine. Using stable-labeled internal standards, the method proved to be accurate and precise for the analytes in all species, resulting in inter-batch accuracy (percent relative error, %RE) within 100 ± 13% and inter-batch precision (relative standard deviation, %RSD) within 11%. Stability was demonstrated for the analytes in neat solutions and the reconstitution solvent, as well as plasma and urine (with or without the deconjugation reagent). The method was simple, robust (utilized for the analysis of several hundred clinical study samples), and amenable to high sample throughput.