Work

A Simple HPLC-DAD Method for the Therapeutic Monitoring of Clozapine and Related Metabolites in Human Plasma and Urine Samples

Year: 2024

Type: article

Abstract: Clozapine and its metabolites require close therapeutic monitoring (TDM) in patients due to poor correlation between the administrated doses and resulting plasma concentrations, the narrow therapeutic interval, high inter-individual variability, and the risk of serious side effects once toxic levels are exceeded. The aim of the study was to develop a simple (relatively cheap) LC-UV method for the quantification of clozapine and its metabolites in plasma and urine samples. For sample preparation, liquid-liquid extraction (LLE) in n-octanol was more efficient and less limiting in injection volumes compared to the in-situ formation of SUPRAS. When analyzing urine, an alkalinization step before extraction was required. The proposed method produced linear concentration responses with/without internal standard (IS) for the target analytes, with LLOQs within the targeted range of 50 ppb and %RSD within the acceptable 15% range. Furthermore, sample stability studies proved that pre-extracted samples were stable for the short term at room temperature and long-term when frozen.

Source: Molecules

DOI: 10.3390/molecules29215039

Authors: Mircea-Alexandru Comănescu, Dana-Maria Preda, Dalia-Simona Miron, Flavian-Ștefan Rădulescu, Victor Voicu, Andrei-Valentin Medvedovici

Institutions: University of Bucharest, Carol Davila University of Medicine and Pharmacy, Romanian Academy

Language: English

Topic: Analytical Methods in Pharmaceuticals

Subfield: Analytical Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,069