Capillary electrophoresis improving clinical measurement of clozapine

dc.contributor.authorHsu, Pei-Chun (Lisa)en
dc.date.accessioned2009-03-30T01:19:09Z
dc.date.available2009-03-30T01:19:09Z
dc.date.issued2008en
dc.description.abstractSchizophrenia is a mental disorder affecting approximately one percent of the population worldwide. The introduction of the second generation antipsychotic drug, atypical antipsychotic, clozapine, has demonstrated 80% reduction in suicide incident. This drug showed effectiveness in the treatment of resistant schizophrenia, however, high concentrations of clozapine and N-desmethylclozapine in plasma exhibit the development of agranulocytosis, a possible lethal blood disorder. Therefore, constant therapeutic drug monitoring is important for patients who receive clozapine. High performance liquid chromatography (HPLC) is the current assay for clinical clozapine measurement. A different assay, the capillary electrophoresis (CE) was explored in this study. It was found the use of a background electrolyte (BGE) concentration of 60 mM, pH at 2.5, temperature at 22 ℃, voltage applied at 10 kV and sample injection at 23 kV for 1.5 seconds is the optimal condition for clozapine separation using a fused-silica capillary 75 μm in internal diameter (i.d.). The use of 75 μm (i.d.) fused-silica capillary not only permits a larger sample size, but also provided longer detection pathlength which increased the limit of detection for CE. One hundred and eight patients’ samples were analysed by CE and compared with HPLC results obtained from the Canterbury Health Laboratory. A linear regression line of 1.100 was obtained. Seven External Quality Control (EQC) samples were also analysed and compared to the HPLC results gained from the EQC program world wide. A linear regression line of 1.008 and 1.043 were obtained from clozapine and N-desmethylclozapine separation respectively. The developed CE method has shown to be a valid assay for clozapine and N-desmethylclozapine separation and a more cost effective method compared to HPLC.en
dc.identifier.urihttp://hdl.handle.net/10092/2260
dc.identifier.urihttp://dx.doi.org/10.26021/6901
dc.language.isoen
dc.publisherUniversity of Canterbury. School of Biological Sciencesen
dc.relation.isreferencedbyNZCUen
dc.rightsCopyright Pei-Chun (Lisa) Hsuen
dc.rights.urihttps://canterbury.libguides.com/rights/thesesen
dc.subjectschizophreniaen
dc.subjectclozapineen
dc.subjectN-desmethylclozapineen
dc.subjectplasmaen
dc.titleCapillary electrophoresis improving clinical measurement of clozapineen
dc.typeTheses / Dissertations
thesis.degree.disciplineBiochemistryen
thesis.degree.grantorUniversity of Canterburyen
thesis.degree.levelMastersen
thesis.degree.nameMaster of Scienceen
uc.bibnumber1126901en
uc.collegeFaculty of Scienceen
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