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.