5 Conclusions

At present, there are relatively many quantitative studies on impurities, but there are still some challenges for the structure analysis of impurities, especially trace impurities. The ICH guidelines clearly point out that it is necessary to analyze the structure of impurities exceeding a certain content in the quality control of drugs. Although the sensitivity of MS can reach the microgram level, there are still some problems in the identification of unknown impurity structures. Because MS only deduces the approximate chemical structure based on the fragmentation law. The structural characterization of impurities also needs to rely on more spectral information, such as NMR, infrared spectroscopy. However, the sensitivity of NMR spectroscopy is poor, and the structural characterization of trace impurities is still a huge challenge. Due to the small amount of impurities in the sample, it is not easy to obtain a large amount of impurities by preparative HPLC. The impurity can be enriched by forced degradation and directed synthesis, so that the impurities in the sample can reach the detection line and purity, but this method does not solve all the impurity problems. Improving the sensitivity of NMR and the system of LC - NMR may be solutions to the detection of trace impurities, and it is also the direction that many researchers are working on.
In many cases, the quantification of unknown impurities lacks standard products, so that absolute quantification of impurities cannot be achieved. Some researchers have also established a method of impurity reference substance database 101 to solve this problem. The database provides qualitative parameters of impurity (chromatographic retention time, UV/IR, MS and NMR) and quantitative parameters of impurity (principal component response factors). It is also a good choice to solve the accurate quantification of impurities.