Novel Identification of Cysteinyl Derivatives of Toxic Clozapine Nitrenium Ions and the Effect of Valproic Acid on Metabolite Formation: A Study Using Reprocessed High-Resolution Mass Spectra of Analyzed Therapeutic Drug Monitoring Samples.

Birgit M WollmannAina G HaugenRobert L SmithEspen Molden

Published in: Therapeutic drug monitoring (2024)

A novel method for detecting cysteinyl conjugates of CLZ was developed. Application of this method indicated that VPA significantly increased the formation of CLZ-Cys 1+ metabolites, which might explain the granulocyte toxicity reported after adding VPA to CLZ treatment. The developed method opens new avenues for investigating CLZ toxicity, e.g. by correlating cysteinyl conjugates and granulocyte counts in patients.

Keyphrases

high resolution
end stage renal disease
peripheral blood
chronic kidney disease
newly diagnosed
peritoneal dialysis
ms ms
cancer therapy
patient reported
smoking cessation
tandem mass spectrometry