Development and validation of a liquid chromatography-tandem mass spectrometric method for the determination of the major metabolites of duloxetine in human plasma.

A sensitive bioanalytical method for the measurement of two major circulating metabolites of duloxetine [4-hydroxy duloxetine glucuronide (LY550408) and 5-hydroxy-6-methoxy duloxetine sulfate (LY581920)] in plasma is reported. This method produced acceptable precision and accuracy over the validation range of 1-1000 ng/mL. Several issues had to be addressed in order to develop an LC/MS/MS assay for these metabolites.