Application of MALDI-QTOF mass spectrometry to the determination of timiperone in whole blood, and estimation of its new metabolites in urine of a deceased subject who had been treated with timiperone antemortem

Application of matrix-assisted laser desorption ionization (MALDI) quadrupole time-of-flight (QTOF)-mass spectrometry (MS) to the determination of timiperone and estimation of its phase I metabolites were performed for the first time. The limit of detection of timiperone in human whole blood was 1 ng/mL with a quantitation range of 2–100 ng/mL using 20 μL each of whole blood. The developed method was successfully applied to the determination of timiperone in whole blood obtained from a deceased subject that had a history of timiperone treatment. The concentration of timiperone in whole blood of the victim was 3.98 ng/mL. Moreover, the MALDI-QTOF-MS/MS method was also used for detection of new metabolites of timiperone in urine also obtained from this victim. Five new metabolites were detected, which were formed via exchange of S for O, deletion of S, carbonyl reduction, hydroxylation, and a combination of them. Most likely, some of the newly detected metabolites seem pharmacologically active because they retain butyrophenone structures.