Quality control of pharmaceutical intermediates is a key step to ensure the quality and safety of the final drug. The following are several common quality control methods for pharmaceutical intermediates:
1. Thin layer chromatography (TLC)
Thin layer chromatography is a commonly used qualitative analysis method that can be used to detect impurities and purity in intermediates. By comparing the color and position of the sample spots with the standard, it can be determined whether the quality of the intermediate meets the standard.
2. High Performance Liquid Chromatography (HPLC)
High Performance Liquid Chromatography is a highly sensitive analytical method that can be used to detect specific components and impurities in intermediates. By selecting appropriate chromatographic columns and mobile phases, various components in intermediates can be effectively separated and detected.
3. Capillary Gas Chromatography (GC)
Capillary gas chromatography is suitable for detecting volatile substances, such as residual solvents. By selecting appropriate chromatographic columns and temperature programs, various volatile impurities in intermediates can be effectively separated and detected.
4. Spectrophotometric colorimetry
Spectrophotometric colorimetry can be used to determine specific components in intermediates, such as total polysaccharide content. By measuring the absorbance of the sample at a specific wavelength, the content of the target component in the sample can be calculated.
5. Impurity control strategy
Impurity control strategy is the core of quality control of pharmaceutical intermediates. It is necessary to formulate corresponding test items and limit standards based on the synthesis process and impurity characteristics. For example, if palladium carbon catalyst is used in the process, it is necessary to evaluate the palladium residue in the API and formulate corresponding control strategies.
6. Risk assessment
When formulating intermediate quality standards, a comprehensive quality risk assessment is required, including properties, related substances, isomers, residual solvents, genotoxic impurities, metal ions, ignition residues, heavy metals, moisture, crystal form, particle size, etc. Find out the key control points of API quality risks in the process and formulate corresponding control strategies.
The above methods can be used alone or in combination according to the specific situation to ensure that the quality of pharmaceutical intermediates meets the standards, thereby ensuring the safety and effectiveness of the final drug.