Capillary electrophoresis improving clinical measurement of clozapine (2008)
Type of ContentTheses / Dissertations
Degree NameMaster of Science
PublisherUniversity of Canterbury. School of Biological Sciences
Schizophrenia 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.
Keywordsschizophrenia; clozapine; N-desmethylclozapine; plasma
RightsCopyright Pei-Chun (Lisa) Hsu
Showing items related by title, author, creator and subject.
Does dissociation mediate the relationship between childhood abuse and auditory hallucinations? An investigation using clinical samples with schizophrenia and dissociative identity disorder. Nesbit, Amy J. (University of Canterbury, 2018)Previous research has found that the relationship between childhood trauma and auditory hallucination is mediated by dissociation (Perona-Garcelan et al., 2012a, 2014) and that the specific types of dissociation that mediate ...
Osborn, Anna (University of Canterbury. Biological Sciences, 2006)The oxidation of lipids and antioxidants has been extensively studied in human plasma but little attention has been given to how plasma proteins are oxidised. Proteins make up the majority of biomolecules in cells and ...
Virtual Patients and Clinical Trial Simulations to Improve Safety of Glucose Control in Intensive Care Fisk, L.; Le Compte, A.J.; Shaw, Geoff; Chase, Geoff (University of Canterbury. Mechanical Engineering, 2012)Despite the potential clinical benefits of normalizing blood glucose in critically ill patients, the risk of hypoglycemia is a major barrier to widespread clinical adoption of accurate glycemic control. To compare five ...
Clinical Data Validation of an improved, physiologically relevant Critical Care Glycaemic Control Model Pretty, C.G.; Parente, J.; Razak, N.; Lin, J.; LeCompte, A.J.; Shaw, Geoff; Hann, C.E.; Chase, Geoff (University of Canterbury. Mathematics and StatisticsUniversity of Canterbury. Mechanical Engineering, 2008)Introduction: Stress induced hyperglycaemia is prevalent in critical care. Tight glycaemic control is associated with significantly improved clinical outcomes. Providing tight control is difficult due to evolving patient ...
Heitz, Alexandre (University of Canterbury. HIT Lab NZ, 2013)The term Virtual Patient (VP) refers to the use of virtual characters which embody patients in a virtual environment. They are implemented in computer simulations to create realistic clinical encounters. VPs have been used ...
A Randomized, Double-Blind, Placebo-Controlled, Prospective Clinical Trial Evaluating Water-Soluble Chicken Eggshell Membrane for Improvement in Joint Health in Adults with Knee Osteoarthritis Hewlings S; Kalman D; Schneider LV (Mary Ann Liebert Inc, 2019)Osteoarthritis (OA) is a chronic condition that impacts quality of life and functionality for which consumers often seek dietary supplements to provide some relief. The purpose of this double-blind, placebo-controlled ...