Drug impurities are related to the quality of drugs, which is a key quality attribute and a key research object in the chemical drug development process.
Generally speaking, chemical impurities are classified into organic impurities and inorganic impurities according to the structure. The impurities and potential impurities actually present in the drug are organic impurities, and the organic impurities are further classified into process impurities and degradation impurities.
Process impurities include starting materials, intermediates, actuals, ligands, and catalysts.
Degradation of impurities refers to impurities produced by chemical changes in the drug substance and preparation during production and storage. Some process impurities may also be degradation impurities.
The various impurity inspection items specified in the Pharmacopoeia refer to impurities that may be contained or produced and controlled during the production and normal storage of the drug.
Impurities that are not specified in the Pharmacopoeia are generally not required to be inspected. For impurities that endanger human health and affect the stability of drugs, the limits must be strictly controlled.
Research methods for degrading drug impurities
I. Influencing factors Experiments can study drug degradation impurities
For example, some researchers investigated the influencing factors of fasudil hydrochloride injection and identified its photodegradation products. The method is to carry out high temperature and light treatment on fasudil hydrochloride injection, and analyze the impurities by liquid chromatography-mass spectrometry to identify the photodegradation products.
The influencing factors test showed that fasudil hydrochloride injection was placed under high temperature for 10 days, and there was no significant change in each test item, indicating that the drug was stable under high temperature conditions. Under light conditions, the drug can produce a photodegradation impurity, isoquinoline-5-sulfonic acid, indicating that it is unstable under light conditions and should be stored in the dark.
Second, structural characteristics analysis to obtain possible degradation products
Based on structural features, identification, structural analysis and quantitative determination of impurities and degradation products from pharmaceutical raw materials and pharmaceutical formulations can analyze possible degradation products
In order to improve the safety of drug treatment, impurities should be identified and determined by selective methods, and impurity analysis has become an important part of modern pharmaceutical analysis.
Third, the forced degradation test to obtain the degradation impurity peak
For example, some researchers have used a forced degradation method to obtain the degradation impurity peak of irilidepine bulk drug, and analyzed the impurity of the drug substance.
The researcher systematically analyzed the composition of the degradation spectrum of domestically produced iraidipine bulk drug, and determined the degradation route, type and limit of impurities in the drug substance by comparing the foreign pharmacopoeia.
In the study of drug synthesis, the influencing factors and the results of the forced degradation test should be closely monitored, which will help to study the mechanism of impurity generation. The study found that most of the degradation impurities can be found by influencing factors and forced degradation experiments.
For the unknown impurities, the impurities should be obtained by synthesis and separation and structural confirmation. The impurities are difficult to obtain at one time.
Of course, some impurities are not produced in the experiment, but are generated during long-term placement. Therefore, it is very important to periodically test the samples for a long time. It is found that new impurities must be highly valued.
