Work

Identification of N -debenzisothiazole-lurasidone as an enzymatic degradation product of lurasidone

Year: 2025

Type: article

Abstract: Herein we report the confirmation of N-debenzisothiazole-lurasidone as a lurasidone degradation product associated with postmortem toxicology casework. Confirmation was realized by unambiguous synthesis and comparison of its LC-MS/MS properties to the lurasidone degradation product in postmortem blood using liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-QTOF/MS). The mechanism of formation of this degradant in blood is proposed to be primarily enzymatic, given it has only been previously presumptively reported in one in vitro stability study following oxidative stress conditions. It has not been reported in other in vivo pharmacokinetic and in vitro stability studies assessing lurasidone stability toward acid, alkali, oxidation, photolysis, and heat. The detection of N-debenzisothiazole-lurasidone in postmortem casework indicates that, where possible, it should be included in toxicology screening methods targeting psychoactive compounds. Until such time that a commercially available reference standard of N-debenzisothiazole-lurasidone is available, the comprehensive accurate mass and mass spectral data of N-debenzisothiazole-lurasidone that are now available enable its inclusion as a "suspect target" in high-resolution MS screening methods.

Source: Journal of Analytical Toxicology

DOI: 10.1093/jat/bkaf097

Authors: Kyle Farrell, Tristan Fraser, Danielle Butzbach, Jared Castle, Kenneth Paul Kirkbride

Institutions: Victorian Institute of Forensic Medicine, Flinders University

Language: English

Topic: Forensic Toxicology and Drug Analysis

Subfield: Toxicology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,823