The analysis of clozapine and norclozapine in plasma using automated on-line sample preparation and LC–MS/MS
Clozapine is a dibenzodiazepine drug used in the treatment of schizophrenia. It is uniquely effective in patients resistant to therapy with other antipsychotics. In addition to mandatory haematological monitoring to minimize the risk of agranulocytosis, there is a large variation (50-fold) in clozapine dose requirement that complicates dose assessment. Clozapine is metabolized via N-demethylation, N-oxidation, and aromatic hydroxylation, amongst other pathways. N-Desmethylclozapine [norclozapine], accumulates in plasma to concentrations similar to those of clozapine. Clozapine N‑oxide accumulates in plasma to approximately 10% of the plasma clozapine concentration but is not measured routinely. Changes in smoking habit can have a large effect on clozapine dose requirement. On average the clozapine dose for non-smokers is half that required for smokers due to induction of the cytochrome P450 enzyme in CYP1A2 smokers. Accurate measurement of plasma clozapine and norclozapine concentrations may help understand issues related to dose optimization and adherence. Current methodology in our research laboratory for plasma clozapine and norclozapine measurement involves off-line liquid-liquid extraction (LLE) into methyl tert-butyl ether at pH 10.6 with manual transfer of the extract to an HPLC-UV system. Clozapine N-oxide is not extracted.
Carol Robinson Awarded 2024 Lifetime Achievement European Inventor Award
July 24th 2024Carol Robinson of the University of Oxford has received the European Inventor Award 2024 for Lifetime Achievement from the European Patent Office for her work bringing mass spectrometry to structural biology.
Microseparations and Analysis Covered at HPLC 2024
July 23rd 2024At HPLC 2024 in Denver, Colorado, various sessions will be led by experienced scientists, covering different aspects of chromatography techniques and maximizing their effectiveness. Here is some information about tomorrow’s sessions.
Automated LC Method Development: An HTC-18 Interview with Bob Pirok
July 23rd 2024At HTC-18 in Leuven, Executive Editor of LCGC International, Alasdair Matheson, spoke to this year’s winner of the 2024 HTC-18 Innovation Award, Bob Pirok from the University of Amsterdam, about his innovative research on automated LC method development.