Studies On Liquid Chromatography Coupled With Electrospray Ionization High Resolution Mass Spectrometry Applying In Compounds Structure Characterization

It could get abundant chemical information which included the retention time,uv-vis spectrum information, accurate molecular weight and the structural fragmentsof the compound by the LC-UV-ESI-HRMS technology. The mutual authenticationof the information will strengthen the reliability of the experimental results. Currently,structure confirmation of compounds and the development of new drugs rely moreand more on the application of LC-ESI-HRMS.The paper reviewed the principle and the advanced applification in the field ofpharmaceutical analysis of the LC-ESI-HRMS. Then two part of works were carriedout based on it.1. A electrospray ionization-high resolution mass spectrometry (ESI-HRMS)method was developed for the determination of thermolabileN,N-dimethylaminomethyl ferrocene compounds. The relative standard deviation(RSD, n=10) for the ion counts of our target molecule was2.4%. By analysis of theMS spectrum and MS/MS spectrum of the target molecule, it is showed that anin-source dissociation of the target molecule took place with the abundance of themother ion being less than10%of the abundance of the main daughter ion in the MSspectrum. The relevance of ion counts of the target molecule and its main daughterion with the temperature of the drying gas and the voltage of the capillary export(Fragmentor) were investigated respectively. Furthermore, corresponding fittingmathematical equations were established. Finally, the optimum analytical conditionsof the target molecule by ESI-HRMS were abtained.2. A HPLC-UV-ESI-MS method for the analysis of tebipenem pivoxil and itsrelated impurities was established and optimized. The LC peaks were qualifiedaccording to the retention time, accurate molecular weight, and UV max absorption.3. MS/MS characteristicses of tebipenem pivoxil and its related impurities werestudied and the fragmention pathes were elaborated. The breakage of the covalent bond of C-C, C-N and C-O, the inner molecular rearrangement and the losing of theneutral small molecules such as CO, CO2, HCHO, H2O were took placed during CID(collision induced dissociation). The regular MS/MS fragmentation pattern could besummarized due to the similar molecular structures of tebipenem pivoxil and itsrelated impurities. The conclusion would not only contribute to the pharmic andclinical research of tebipenem pivoxil, but also provide valuable references for thenew drug research and development of the structural analogues of tebipenem pivoxil.