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UBC Theses and Dissertations

Determination of small medicinal molecules by capillary electrophoresis mass spectrometry with on-line concentration techniques Zhao, Tingting


Capillary electrophoresis (CE) is a powerful separation technology. CE has various advantages over other separation techniques (e.g. LC) including fast speed, separation efficiency and small solvent consumption. However, the small inner diameter of capillary and short optical path result in low sensitivity of CE for trace analytes. The poor detection limit restricts the wider application of CE. In this study, on-line preconcentration methods were developed to improve the detection sensitivity of normal capillary electrophoresis coupled with mass spectrometry (CE-MS). In Chapter 2, a field assisted sample stacking (FASS) technique was adopted for the quantification of imatinib (Gleevec), a drug approved for the treatment of chronic myeloid leukemia. In FASS, acetonitrile was used to dissolve the sample in order to enhance the electrical field strength in sample plug during initial CE separation. After optimization, baseline separations of imatinib with related compounds were obtained and detection sensitivity was improved by 8-fold. The sample pretreatment was simple and the LOD of 0.2 ng/mL was achieved for imatinib. Validation tests suggested this FASS-CE-MS method has a wide linearity range, high specificity, acceptable precision and accuracy. In Chapter 3, acid barrage stacking (ABS) with CE-MS was used for the determination of alendronate sodium (Fosamax)- a drug used for the treatment of osteoporosis disease. This is the first ABS-CE-MS method for direct ALN analysis. Following sample injection, an acid barrage was introduced into separation capillary. The acid segment works as a barrier to stop the migration of negatively charged ALN ions and stacks them on the boundary. After optimization, the detection sensitivity was improved by 810-fold compared to normal capillary electrophoresis. The limit of detection achieved was 2 ng/mL for ALN. Relative peak area and concentration of ALN showed excellent linear relationship in the range of 8 - 2000 ng/mL (R²>0.9990). This method was successfully used for quantification of ALN in drug tablet. Validation results showed good repeatability and accuracy of this method. Both online concentration methods -- FASS and ABS significantly improved the detection sensitivity of CE-MS. In addition, these two methods are easy-to-use and compatible with normal capillary electrophoresis system, which make them applicable for routine biological sample analysis.

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