+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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



Journal of Pharmaceutical & Biomedical Analysis 26(2): 301-311



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 multiple reaction 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/z 256 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 used for 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 variations for 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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 011362470

Download citation: RISBibTeXText

PMID: 11470207

DOI: 10.1016/s0731-7085(01)00410-1


Related references

Determination of ziprasidone in human plasma by liquid chromatography-electrospray tandem mass spectrometry and its application to plasma level determination in schizophrenia patients. Journal of Chromatography. B Analytical Technologies in the Biomedical and Life Sciences 847(2): 237-244, 2007

Simultaneous determination of sibutramine and its N-desmethyl metabolites in human plasma by liquid chromatography-electrospray ionization-mass spectrometry. Method and clinical applications. Analytica Chimica Acta 492(1-2): 241-248, 15 September, 2003

Simultaneous Determination of Celecoxib, Erlotinib, and its Metabolite Desmethyl-Erlotinib (OSI-420) in Rat Plasma by Liquid chromatography/Tandem Mass Spectrometry with Positive/Negative Ion-Switching Electrospray Ionisation. Scientia Pharmaceutica 80(3): 633-646, 2012

Simultaneous determination of ten antiepileptic drugs in human plasma by liquid chromatography and tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application in therapeutic drug monitoring. Journal of Separation Science 39(5): 964-972, 2016

Development and validation of a sensitive method for simultaneous determination of rosuvastatin and N-desmethyl rosuvastatin in human plasma using liquid chromatography/negative electrospray ionization/tandem mass spectrometry. 2013

Development and validation of a sensitive method for simultaneous determination of rosuvastatin and N-desmethyl rosuvastatin in human plasma using liquid chromatography/negative electrospray ionization/tandem mass spectrometry. Biomedical Chromatography 27(11): 1369-1374, 2013

Simultaneous Determination of Eight Ginsenosides in Rat Plasma by Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry: Application to Their Pharmacokinetics. Molecules 20(12): 21597-21608, 2015

Development of a method for simultaneous determination of eflucimibe and its three major metabolites in rat plasma by liquid chromatography/electrospray tandem mass spectrometry: a preliminary study. Rapid Communications in Mass Spectrometry 19(3): 297-302, 2005

Simultaneous quantification of rosiglitazone and its two major metabolites, N-desmethyl and p-hydroxy rosiglitazone in human plasma by liquid chromatography/tandem mass spectrometry: application to a pharmacokinetic study. Journal of Chromatography. B Analytical Technologies in the Biomedical and Life Sciences 877(20-21): 1951-1956, 2009

Simultaneous determination of diphenhydramine, its N-oxide metabolite and their deuterium-labeled analogues in ovine plasma and urine using liquid chromatography/electrospray tandem mass spectrometry. Journal of Mass Spectrometry 33(12): 1171-1181, 1998

Simultaneous determination of GFA and its active metabolites in human plasma by liquid chromatography electrospray ionization mass spectrometry and its application to pharmacokinetic studies. Journal of Pharmaceutical and Biomedical Analysis 46(4): 728-736, 2008

Simultaneous determination of metformin and rosiglitazone in human plasma by liquid chromatography/tandem mass spectrometry with electrospray ionization: application to a pharmacokinetic study. Journal of Chromatography. B Analytical Technologies in the Biomedical and Life Sciences 854(1-2): 91-98, 2007

Simultaneous determination of cyclophosphamide and 4-hydroxycyclophosphamide in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry - application to Chinese systemic lupus erythematosus patients. Clinical Chemistry and Laboratory Medicine 49(12): 2029-2037, 2011

Simultaneous quantification of oleuropein and its metabolites in rat plasma by liquid chromatography electrospray ionization tandem mass spectrometry. Biomedical Chromatography 24(5): 506-515, 2010

Simultaneous determination of apatinib and its four major metabolites in human plasma using liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study. Journal of Chromatography. B Analytical Technologies in the Biomedical and Life Sciences 895-896: 108-115, 2012