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Simultaneous Determination of Thioridazine and Its Metabolites by UHPLC–MS/MS With Application to a Pharmacokinetic Study in Rats

Year: 2025

Type: article

Abstract: ABSTRACT To develop an LC–MS/MS method for simultaneous quantification of thioridazine and its metabolites in rat plasma, samples were prepared by protein precipitation and filtration using thioridazine‐d3 as an internal standard. Chromatographic separation was achieved on a reversed‐phase C18 UPLC column with 0.1% formic acid in acetonitrile and 10‐mM ammonium acetate in water at 0.7 mL/min. Quantification was performed using multiple reaction monitoring in positive ion mode with the following precursor–product ion transitions: m/z 371.1 → 126.1 (thioridazine), m/z 387.1 → 126.1 (mesoridazine), m/z 403.1 → 126.1 (thioridazine‐2‐sulfone), m/z 387.2 → 126.1 (thioridazine‐5‐sulfoxide), and 374.1 → 129.1 (thioridazine‐d3). This method showed good linearity: 0.1–1000 ng/mL for thioridazine ( r 2 = 0.9980) and 0.5–1000 ng/mL for mesoridazine ( r 2 = 0.9981), thioridazine‐2‐sulfone ( r 2 = 0.9976), and thioridazine‐5‐sulfoxide ( r 2 = 0.9967). The accuracy of the LLOQ and QC samples for thioridazine and its metabolites was within 85%–115%, with intrabatch and interbatch precisions (CV%) below 15%. The average recovery ranged from 98% to 109%, and no significant matrix effect was observed, with values ranging from 93% to 110%. All analytes were stable under the conditions used in this study. This method was applied in a pharmacokinetic study following the intravenous administration of thioridazine to rats.

Source: Biomedical Chromatography

DOI: 10.1002/bmc.70298

Authors: Kyung‐Sun Moon, Jong‐Min Song, Sung‐Hoon Ahn

Institution: Kangwon National University

Language: English

Topic: Analytical Methods in Pharmaceuticals

Subfield: Analytical Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: bronze