A Acridinium Ester Chemiluminescence System For Capillary Electrophoresis-chemiluminescence Analysis And Its Application In Pharmaceutical Analysis

With the improvement of living standard and medical treatment conditions, the public is paying attention to medication safety. Therefore, the work for therapeutic drug monitoring is more and more important for guaranteeing safe medication. The improvement and update of the methods for therapeutic drug monitoring are facing great challenge due to the variety and complexity of compounds in biological samples. The establishment of simple, rapid, highly sensitive and selective strategy for pharmaceutical assay is the key course for analysis of drugs in vivo. Capillary electrophoresis (CE) method is a micro separation technique which has been one of the most widely studied courses in analytical sciences due to its short separation time, high separation efficiency and low sample consumption et al. Different separation modes for CE have been developed with the update of analysis strategy which could meet different demands for various compounds. Thus, the CE technique has been widely used in monitoring and analysis for drug and its metabolites in biological samples. Nevertheless, highly sensitive detections for CE are required for achieving satisfactory detection result in biological samples, due to the mico injection volume of CE analysis. Although laser induced fluorescence (LIF) and mass spectrum (MS) detections could meet the demand for sensitivity for CE, the expensive instrument and complicated process for operation limit their extensive applications. Chemiluminescence (CL) detection is exceptionally famous for its distinguished sensitivity, inexpensive instrumentation and easy operation. To some extent, the sensitivity for CL even equals LIF and MS detection. Therefore, the combination of CE and CL is believed to be a perfect strategy for analytical science, which has shown great potential for pharmaceutical analysis.This thesis focuses on the applications of on-line coupling of CE separation and CL detection technique in pharmaceutical analysis, which used (2’,6’-dimethyl-4’- (N-succinimidyloxycarbonyl)phenyl-10-methyl-acridinium-9-carboxylate-1-propanesu lfonate inner salt (AE) as the pre-column CL derivatization reagent. The content is introduced as followings:A highly sensitive CE-CL strategy was established for the determination of dopamine (DA) and cimbuterol (CM) using AE as derivatization reagent. Under the optimal conditions, the presented method has been successfully applied to analyze DA and CM. The linear ranges were5.0-1500ng/mL and2.0-1000ng/mL with LODs (S/N=3) of2.0ng/mL and0.50ng/mL for DA and CM, respectively. The levels of DA in human urine samples were detected by this method, and the results showed acceptable accordance with those of enzyme linked immunosorbent assay (ELISA) kit. The result of recovery test spiked in urine is83.7%-90.5%. The results have showed satisfactory sensitivity and selectivity. The approach could also be further extended to rapid analysis of many other compounds including primary and second amines in clinical medicine and biopharmaceutical analysis by using AE as CL derivatization reagent.