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Titolo:
Simultaneous determination of clozapine and its N-desmethyl and N-oxide metabolites in plasma by liquid chromatography/electrospray tandem mass spectrometry and its application to plasma level monitoring in schizophrenic patients.
Autore:
Aravagiri, M; Marder, SR;
Indirizzi:
VA Greater Los Angeles Hlth Care Syst, Psychopharmacol Unit, Los Angeles, CA 90073 USA VA Greater Los Angeles Hlth Care Syst Los Angeles CA USA 90073 90073 USA
Titolo Testata:
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
fascicolo: 2, volume: 26, anno: 2001,
pagine: 301 - 311
SICI:
0731-7085(200109)26:2<301:SDOCAI>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
SOLID-PHASE EXTRACTION; ULTRAVIOLET DETECTION; HUMAN SERUM;
Keywords:
clozapine; norclozapine; clozapine N-oxide; simultaneous determination; LC-MS-MS; electrospray; plasma level monitoring;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Aravagiri, M VA Greater Los Angeles Hlth Care Syst, Psychopharmacol Unit, 11301 Wilshire Blvd,Rm 4 B151H Bldg 210, Los Angeles, CA 90073 USA VA Greater Los Angeles Hlth Care Syst 11301 Wilshire Blvd,Rm 4 B151H Bldg 210 Los Angeles CA USA 90073
Citazione:
M. Aravagiri e S.R. Marder, "Simultaneous determination of clozapine and its N-desmethyl and N-oxide metabolites in plasma by liquid chromatography/electrospray tandem mass spectrometry and its application to plasma level monitoring in schizophrenic patients.", J PHARM B, 26(2), 2001, pp. 301-311

Abstract

A liquid chromatography tandem mass spectrometry (LC-MS-MS) assay method for the simultaneous determination of clozapine and its N-desmethyl (norclozapine) and N-oxide metabolites in human plasma is described, The compounds were extracted from plasma by a single step liquid-liquid extraction procedure and analyzed using a high performance liquid chromatography electrospray tandem mass spectrometer system. The compounds were eluted isocratically on a C-18 column. ionized using positive ion atmospheric pressure electrospray ionization method by a TurboIonspray source and analyzed using multiplereaction monitoring mode. The ion transitions monitored were m/z 327 --> m/z 270 for clozapine, m/z 313 --> m/z 192 for norclozapine, m/z 343 --> m/z256 for clozapine-N-oxide and m/z 421 --> m/z 201 for internal standard. The standard curves of clozapine, norclozapine and clozapine-N-oxide were linear over the range of 1 ng/ml to 1000 ng/ml when 0.5 ml of plasma was usedfor the analysis (r(2) > 0.998). Three pooled plasma samples collected from patients who were treated with clozapine were used as long-term quality control samples to check the validity of spiked standard curve samples made at various times. The intra- and inter-assay variations for the spiked standard curve and quality control samples were less than 14%. These variationsfor the long-term patient quality control samples were less than 11%. The LC-MS-MS assay for simultaneous determination of clozapine, norclozapine and clozapine-N-oxide reported here is highly specific. sensitive, accurate and rapid. This method is currently being used for the plasma level monitoring of clozapine and its N-desmethyl and N-oxide metabolites in patients treated with clozapine. The plasma levels of clozapine. norclozapine and clozapine-N-oxide varied widely within and among patients. The data revealed that the norclozapine and clozapine N-oxide metabolites were present at about 58% +/- 14% and 17% +/- 6% of clozapine concentrations in plasma. respectively. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 17/01/20 alle ore 20:10:52