Application Of Various Chromatographic Techniques In Drug Analysis Of Complex System

Separation and detection of complex system components, ionic compounds and hydrophobic compounds, non-UV-absorbing compounds has always been hot and difficult issues in analysis area. HPLC technology are often used to analysis and detect the compounds in complex matrices after multiple centrifugation and extraction. Fast and accurate methods are required to evaluate the quality specifications in actual drug production process, whereas the traditional sample pre-treatment spends a lot of time and resources, which also results in low recovery. Ion-exchange column is usually used for separating the ionic compounds, but if the sample contains hydrophobic compounds besides ionic compounds, it is difficult to achieve satisfying reservations. For weak UV-absorbing materials, UV end absorption detection are often used while sometimes no accurate results can be obtained.This paper aimed to study the application of mixed mode chromatography and universal detector in drug analysis area. With Trichoderma hazianum fermentation broth, ODE-TFV, carboprost tromethamine injection and L-glutamine and sodium gualenate granules as the research objectives, we used two dimensional liquid chromatography, CAD universal detector, mixed-mode column and capillary electrophoresis to develop the analysis method. The established 2D-HPLC method could solve the separation of microscale substance in complex system. Also a capillary electrophoresis method was built up to separate ionic compounds and hydrophobic compounds. In the meanwhile, we used CAD detector to detect no UV-absorbing components to achieve a quantitative detection.This paper established HPLC-UV-CAD method for the simultaneous determination of carboprost, tromethamine and benzyl alcohol in Carboprost Tromethamine injection using mixed-mode column. An on-line two dimensional liquid chromatographic method was also used to separate and detect 2460A from trichoderma hazianum fermentation broth. We also developed the HPLC-CAD method for the determination of non-UV-absorbing component ODE in the sample of ODE-TFV and established a capillary electrophoresis method for the simultaneous determination of L-glutamine and sodium gualenate in L-glutamine and sodium gualenate granules. The established HPLC methods could:(1) evaluate the concentration of 2460A in trichoderma hazianum fermentation; (2) improve the quality control of carboprost tromethamine injection; (3) monitor the residues of ODE in final product of ODE-TFV; (4) simplify the simultaneously detection of L-glutamine and sodium gualenate, which were low-cost, sensitive, simple, accurate and reproducible.This paper used multiple chromatographic technologies to solve different problems in drug analysis. We explored the determination of trace amounts of secondary metabolites in complex matrices, achieved simultaneous detection of polar compounds with opposite charge and verified the application of CAD in the impurities and ion compounds with non-UV absorption. This paper laid the foundation for the further development of mixed mode chromatography and universal detector in the field of drug analysis, and provided new methods for the application of new technologies in the field of drug quality control.