Simultaneous determination of tianeptine and its active metabolite tianeptine MC5 in rat plasma and brain tissue using high performance liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS)

A selective and sensitive method was developed to simultaneously quantify tianeptine and its main active metabolite tianeptine MC5 in rat plasma and brain tissue. A one-step liquid-liquid extraction was developed for sample preparation. The linear range for plasma was from 1.0-500.0 ng mL^-1 and for brain tissue it was from 1.0-500.0 ng g^-1. The method was validated in accordance with US FDA guidelines (precision within 15% relative standard deviation (RSD) and accuracy within 15% relative error (RE) with a consistent recovery). Stable isotope-labeled tianeptine and tianeptine MC5 (tianeptine-D4 and tianeptine MC5-D4) were used as the internal standards achieving good reproducibility while reducing the matrix effects. This method was successfully applied to a preclinical study for the simultaneous determination of tianeptine and tianeptine MC5 in rat plasma and brain tissue.