title: Simultaneous determination of the antipsychotic drugs levomepromazine and clozapine and their main metabolites in human plasma by a HPLC-UV method with solid-phase extraction.
abstract: A HPLC method with UV detection has been developed for the simultaneous determination of levomepromazine, clozapine and their main metabolites: N-desmethyl-levomepromazine, levomepromazine sulphoxide, O-desmethyl-levomepromazine, N-desmethylclozapine and clozapine N-oxide. The analytes were separated on a C8 reversed-phase column using a mobile phase composed of acetonitrile and a pH 2.0, 34 mM phosphate buffer containing 0.3% triethylamine (29:71, v/v). Loxapine was used as the internal standard. A reliable biological sample pre-treatment procedure by means of solid-phase extraction on C1 cartridges was implemented, which allows to obtain good extraction yields (>91%) for all analytes and appropriate sample purification from endogenous interference. The method was validated in terms of extraction yield, precision and accuracy. These assays gave RSD% values for precision always lower than 4.9% and mean accuracy values higher than 92%. The method is suitable for the therapeutic drug monitoring (TDM) of patients undergoing polypharmacy with levomepromazine and clozapine.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Sciences, Alma Mater Studiorum--University of Bologna, Via Belmeloro 6, I-40126 Bologna, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Mercolini
authors.forename: Francesca
authors.initials: F
authors.lastname: Bugamelli
authors.forename: Ernst
authors.initials: E
authors.lastname: Kenndler
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Boncompagni
authors.forename: Livia
authors.initials: L
authors.lastname: Franchini
authors.forename: Maria Augusta
authors.initials: MA
authors.lastname: Raggi
mesh_terms: D014150:Antipsychotic Agents / Q000097:blood*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003024:Clozapine / Q000097:blood*; D006801:Humans; D008728:Methotrimeprazine / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
chemical_list: D014150:Antipsychotic Agents; D008728:Methotrimeprazine; D003024:Clozapine