Abstract
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.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the international and/or national committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individuals included in the study, who supplied about 1 mL each of blood and urine for use as blank samples. The analysis of toxic substances from the cadaver was permitted by judicial authorities with an official document.
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Nozawa, H., Minakata, K., Yamagishi, I. et al. 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. Forensic Toxicol 34, 363–371 (2016). https://doi.org/10.1007/s11419-016-0323-z
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DOI: https://doi.org/10.1007/s11419-016-0323-z