| Antibiotics are a series of drugs with strong biological activities and there is a close relationship between those qualities and the safety of drug usage.With the rapid development of modern analysis technology,more and more attention has been paid to the study of the related substances in antibiotics.Amphotericin B(AmB) that belongs to polyene macrolide antibiotics,has been used clinically for treatment of systematic fungal infections with good effect but also with serious toxicity.In order to strengthen its quality control,it is necessary for us to further study the related substances in this drug.The quality control of multi-component drugs is another hot point in the field of drug analysis.It is well known that one of the common problems in the multi-component drugs is the lack of quality uniformity.In order to guarantee drug quality,ICH introduced a new concept "PAT"(Process Analysis Technology),a system for designing,analyzing,and controlling manufacturing through timely measurements(ie during processing) of critical quality and performance attributes of raw and in-process materials and processes with the goal of assuring final product quality.Hence,strictly controlling the producing process is a key element to warrant multi-component drugs' quality,what's more,the analysis method plays an eye role in the process control.Fingerprint chromatogram technology is suitable for this job, and similarity calculation is used to evaluate the drug quality fluctuation in this method.Angle Cosine method,a classical similarity method,has been applied widely but proved to be low sensitive.Hence,this method needs to be improved in order to get a better sensitivity on the quality fluctuation of multi-component drugs. In recent years,a new technology NIRS(Near Infrared Spectroscopy) develops quickly and this technology has a strong ability to obtain information on line, therefore it may play an important role in the analysis of multi-component drugs.In conclusion,this dissertation mainly refers to several aspects as following:1 The structure and activity study of impurity(2) in Amphatericin B.In this part, firstly,a study was carried out to enrich and separate impurity(2),then its chemical structure was elucidated by use of UV,MS,NMR technologies,at last its activity against Candida albicans was evaluated by micro-dilution method.2 The application of Improved Angle Cosine Method and NIRS Method in the analysis of multi-component drugs.In order to sensitively characterize the quality fluctuation of multi-component drugs,we performed an analysis on the Angle Cosine Method and kitasamycin was used as the study objective.On this basis, Improved Angle Cosine Method was raised and then applied to analyze the simulated and real samples.At last,the feasibility of NIRS in the analysis of multi-component drugs was evaluated.In conclusion,this study provided new methods for the quality control of multi-component drugs. |
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