Construction Of Polymer-Based Capillary Electrochromatography For Separation Of Antipyretic Analgesics And Antibiotics

Antipyretic analgesics and β-lactam antibiotics have been widely used in clinic treatment for fevers,neuralgia,rheumatalgia,and for various antibacterial infections,respectively.However,insufficient medicine dose may not achieve the desired therapeutic effect,while abuse or overdose for long-term may lead to significant side effects,such as carcinogenic effects on human kidneys and bladder,weakening or even disappearing the oxygen-carrying function of hemoglobin,reducing the amount of white blood cells,producing adverse reactions of digestive system,prostration and allergic dermatitis symptoms.In addition,these two kinds of drugs are usually metabolized in the liver and excreted by the kidneys.Therefore,in order to ensure the safe use of antipyretic analgesics and β-lactam antibiotics and further explore their mechanisms,it is worth to developing a quick,accurate and sensitive analysis method and applying the separation of the two kinds of drugs in living body fluids.Facing the problems caused by low sample amount and complicated separation system of living body fluids,capillary electrophoresis(CE)with high efficiency have been widely used in pharmaceutical analysis.Capillary zone electrophoresis(CZE)mode is difficult to get good separation of neutral and structurally similar drugs.Micellar electrokinetic chromatography(MEKC)mode can achieve the baseline separation of drugs by introducing surfactants in running buffer.However,the strong electrolyte salts used in MEKC can contaminate the ion source of a mass spectrometry(MS)and reduce the signals,which would greatly limit the application of CE-MS in the analysis of unknown drugs.Therefore,there is necessary to explore functional materials to improve separation selectivity and achieve high efficient separation by open tubular capillary electrochromatography(OT-CEC)method,instead of using organic solvents or surfactants for the analysis of such drugs.Although varieties polymer materials have been used for OT-CEC,develop novel polymer materials is still a problem:(1)how to design new polymer materials with high selectivity for the antipyretic analgesics and β-lactam antibiotics;(2)how to construct the OT-CEC separation system with multi-functional polymers as the coating.Therefore,based on the differences in the chemical structure and physicochemical properties of the drugs,three new multi-functional polymers have been designed to establish a novel OT-CEC system:(1)Based on the prepared amphipathic block co-polymer poly(styrene-glycidyl methacrylate)coating,multi-functional block co-polymer based coating was used to design a new OT-CEC protocol for the efficient separation of antipyretic analgesics.The block co-polymer was synthesized via reversible addition-fragmentation chain transfer(RAFT)polymerization,and anchored on the capillary surfaces by physical absorption strategy due to the good ability of forming membrane provide by polystyrene moiety.The separation mechanism based on hydrophobic and hydrogen bonding interaction between amphipathic block co-polymer coating and the drugs was also explored,which could achieve high separation efficiency by micellar-like mechanisms and successfully utilized in antipyretic analgesics analysis in rat serum samples.(2)Based on the prepared amphipathic block co-polymer poly(styrene-2-(dimethylamino)ethyl methacrylate)coating,a unique OT-CEC system with block co-polymer coating was constructed for efficient separation of β-lactam antibiotics.The block co-polymer was synthesized through RAFT polymerization,and physical absorption strategy was used to modify capillaries to get better stability and repeatability.Based on the micelle-like interaction between block co-polymer coating and the drugs,the novel OT-CEC system could obtain high separation efficiency and high selectivity.(3)Based on the hydrophobic/hydrogen interaction of homopolymer poly(N-acryloxy succinimide)coating and the analytes,the functional homopolymer based coating was employed in constructing a new OT-CEC system for the separation analysis of antipyretic analgesics.The homopolymer was synthesized by RAFT polymerization,and chemically bonded to the inner surface of capillaries.The new OT-CEC system with good stability and repeatability was successfully used in the analysis of antipyretic analgesics in human urine samples.The separation mechanism based on hydrophobic and hydrogen bonding interaction between homopolymer coating and drugs was also discussed.This paper focus on the harmful to ecological and environment of organic additives in CZE mode and the limitation of CE-MS application due to the surfactants in MEKC,explored the three kinds of functional polymers,a new OT-CEC system with homopolymer and two kinds of block co-polymer based coating were developed to improve the separation efficiency of antipyretic analgesics and β-lactam antibiotics without using organic solvent and surfactant in running buffer.The results show that due to the designed multifunctional polymers providing specific interactions with antipyretic and β-lactam antibiotic,the new OT-CEC system could be successfully used for drugs analysis in living body fluids.