Impurity is a key quality attribute of drugs. Related substances generally refer to the organic impurities in the drug, and its chemical structure is similar to or related to the API. Related substances are crucial and difficult items in the quality control of generic drugs, and analytical methods with superior specificity and high sensitivity are needed to control them accurately and effectively.
Our Services
Research on related substances is the basis for formulating scientific quality standards, and it is also an important guarantee of drugs' safety and efficacy. Our analytical methods for related substances are developed based on the characteristics of the drug, with reference to the pharmacopoeia and RLD, so as to avoid the situation of incomplete or excessive research on impurities.
Our company has an advanced analysis strategy. For substances without UV absorption, we provide RI and other methods. For most UV-absorbing substances, chromatographic methods such as HPLC are usually employed. Our related substances analysis methods can help generic drug companies control product quality, and we provide targeted impurity control strategies to help them comply with regulations and accelerate the market.
Our ideas for method development
The related substances method needs to analyse all the impurities that should be controlled. The synthetic route of API is the key to the study of related substances. By studying the process route, the source and destination of each impurity can be analyzed, and the production mechanism of each impurity is summarized.
- Determination of the limits
For the limits of known impurities or total impurities, we refer to the existing standards of the national pharmacopeias and control with the strictest limits. For unknown impurities, we search the RLD instructions or literature to determine the maximum daily dose of the drug. The limits of corresponding impurities are determined according to the relevant provisions of ICH guidelines. It is notable that the ICH guideline for substance reporting limits is 0.05%, which is for product inspection and release criteria. In the formulation process research stage, we suggest not arbitrarily ignoring the content of less than 0.05% of the related substances, and avoid ignoring some degradation trends or other characteristics of the product.
Determination of analytical methods
- Pharmacopoeia method reappearance
For the items included in the national drug standards, the detection methods in the standards should be considered first. If there are multiple methods for the detection of related substances, it is necessary to reproduce different methods and conduct comparative studies. Generally, we confirm the feasibility of the method by using impurity reference materials or by forced degradation tests.
- Optimization of analytical methods
The analytical methods of generic drugs should refer to the pharmacopoeia standard or the detection method of RLD. When the existing method is not completely suitable for a particular project, it is necessary to optimize the method reasonably.
- The appropriate detection wavelength is selected according to the UV absorption spectrum of each related substance.
- The pharmacopoeia method is adjusted and optimized according to the physical and chemical properties and structural characteristics of the related substances in the client's generic drug project.
- Investigation of the preparation method for the test solution
In cases where the stability of the drug is not good or the active ingredient is difficult to effectively extract from the preparation, we will investigate the influence of operating environment, preparation time, ultrasound, shaking and other methods. We will conduct rigorous comparative experiments to finally determine a suitable and durable formulation.
Validation of methods
- System suitability
- Specificity
- Detection limit
- Quantification limit
- Linearity and range
- Accuracy
- Stability
- Precision
- Durability
