Development Of New Capillary Electrochromatography For Analysis Of Antipyretic Analgesic Drugs

Antipyretic analgesics are a class of non-steroidal anti-inflammatory drugs that have antipyretic,analgesic,anti-inflammatory and anti-rheumatic,which can act on the central nervous system.However,due to the troublesome side effects,such as the risk of agranulocytosis,methaemoglobinaemia,and possesses a potential carcinogenic effects on bladder,kidney and other organs,its application has been limited.Therefore,analysis and monitoring the antipyretic analgesics in samples have become necessary for quality control of these drugs on administration and clinical medication safety.A great number of chromatographic methods have been developed for analysis of antipyretic analgesics,such as high performance liquid chromatography,gas chromatography,thin layer chromatography,supercritical fluid chromatography and capillary electrophoresis.Capillary zone electrophoresis(CZE),micellar electrokinetic chromatography(MEKC)and capillary electrochromatography(OT-CEC)are common modes of capillary electrophoresis,which have been well performed in drugs analysis due to their advantages in traceable samples and solvents consuming,high separation efficiency and rapid analysis.Owing to the similar chemical structure and mass-to-charge ratios of analyzed,baseline separation of antipyretic analgesics by using CZE method could not be achieved.MECK can realize baseline separation of those compounds.However,substantial surfactants in running buffer of this method might cause interfere effect on the stability of MEKC system.Moreover,these surfactants would induce serious contamination of the ion source in mass spectrometry system once unknown drugs are analyzed by capillary electrophoresis-mass spectrometry method.Therefore,it is urgent to explore novel capillary electrophoresis technique for separation of antipyretic analgesics without adding surfactants in buffer solution.This is also of great significance for quality control of drugs on administration and the clinical medication safety.Until now,the researchers still faced enormous challenges in OT-CEC study,such as how to improve the separation efficiency of OT-CEC,less species of polymer monomers that used as OT-CEC coatings,narrow range of applications and so on.To solve those problems,one of the potential strategies is to find the novel materials as polymer coating and to use ionic liquids as electrolyte additives.The polymer coating included self-assembly block co-polymers which could expand the range of applications of OT-CEC and construct a unique OT-CEC system.This dissertation focuses on the improvement of separation efficiency and expanding the types of polymer coatings to construct a novel OT-CEC system.The specific research contents are as follows:(1)The significance and value of pharmaceutical analysis study,the progress of MEKC,CEC and antipyretic analgesics are briefly introduced.Consequently,the challenges and research contents of this dissertation are put forward;(2)The research progress of MEKC in drug analysis was briefly described,the separation efficiency of antipyretic analgesic drugs were obviously enhanced by using MEKC.This protocol provided a platform for the future development of new polymer materials in novel OT-CEC system construction for clinic antipyretic analgesic drugs analysis;(3)The block copolymer was prepared by reversible addition fragmentation chain transfer polymerization method and applied in the capillary inner wall through chemical covalent bonding.Interestingly,by adding organic solvent into the running buffer,the amphipathic block copolymer coating could self-assemble to form micelle spheres and play the role of surfactants.Meanwhile,the improving separation efficiency mechanism of the coating in OT-CEC was explored briefly.Furthermore,the developed OT-CEC technique was successfully used to analyze the antipyretic drugs in real tablets;(4)A unique OT-CEC system was developed with the ionic liquids as electrolyte additives.The ionic liquid could promote the self-assembly of the amphiphilic block polymer in micelle structure formation,which avoid the environmental pollution caused by the added traditional organic solvents.This proposed method was applied to quantitative analysis of antipyretic analgesics in rat blood;(5)Summary and prospect of OT-CEC.