Application Of Electrospray Mass Spectrometry Coupling With High Performance Liquid Chromatography On Pharmaceutic Analysis

Mass spectrometry is an important instrument in the modern analysis technology. In particularly, the development of electrospray ionization (ESI) source enhances the ionization ability, and shows the advantages of mass spectrometer in the widely applied area. Several applications were built up and developed in this thesis to separate, analyze, recognize, and study the synthesized Pharmaceuticals, natural products, and metal ion-coordinated oligosaccharides by ESI-MS and coupled with HPLC.1. A simple high-performance liquid chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS) method for the separation and characterization of synthetic impurities of triclabendazole has been developed. Application of the on-line HPLC/ESI-MS examinations performed by using ion trap analyzer with TIC and EIC technique in positive or negative ion modes, two impurities about 0.1% content were detected and identified as 5-chloro-6-(2,3,4-trichlorophenoxy)-2-methylsulfanyl-1H-benzoimidazole and 5-chloro-6-(2,3-dichlorophenoxy)-l-methyl-2-methylsulfanyl-1H-benzoimidazole. Meanwhile, some intermediates of impurity-1 were tracked and confirmed the origin of impurities.2. With the TIC and EIC and HPLC/ESI-MS~n techniques, we recognized the 7 compositions, lincomycin, 7-epilincomycin, clindamycin B, dehydroclindamycin, 7-epiclindamycin, clindamycin diastereisomer, and clindamycin in the crude product of clindamycin. Because of the few limitation and wide applications, mass spectrometer is advanced and indispensable in the area of pharmaceutical analysis.3. We investigated a simple and rapid method for identification of vinca alkaloids from crude extract of Catharanthus roseus G Don (Apocynaceae) by direct-injection ESI and tandem mass spectrometry (MS/MS). For characterization of different fragment fingerprints, the 4 vinca alkaloids, vindolidine, vindoline, vinblastine, and vincristine were evaluated in the C. roseus commercial extract by direct-injection ESI-MS/MS, and the results were proved by HPLC/ESI-MS with reference samples.4. By direct-injection ESI and ESI-MS~n, we also studied the three alkaloids, liensinine,isoliensinine and neferine in the Nelumbinis Plumula. With the characterized fragmentation and detailed fragment mechanism, the fingerprints of these three alkaloids in the mass spectra were constituted and applied on the rapid corroboration of the alkaloids in the Nelumbinis Plumula extracts. On the other hand, the results were all confirmed by HPLC/ESI-MS".5. hi the work presented herein, ESI-MS were used to better understand the relationship between alkali metal ions or transition metal ions and oligosaccarides to promote the studies and discovery of the interaction, binding abilities, structure effects and functions by electrospray mass spectrometry. MS/MS is also employed in order to probe carbohydrate structure. From CID abundant information, it is possible to decipher the oligosaccharides composition, sequence linkages, and structures. These are good knowledge and evidences for the researches of metal ion-saccarides systems in the liquid phase.