Medicilon’s analytical chemistry and purification separation team provides customers with high-quality analysis and purification separation services. Our experts are highly recognized by customers for their rich experience and proficient skills in problem solving. We mainly provide the following services:
Separation and supervision of impurities in starting materials, intermediates, APIs and pharmaceutical products using various techniques such as HPLC Collect complete 1D/2D NMR, LCMS, EA, HRMS, IR, UV and other data to identify the structure of the separated impurities Separation and structure identification of API forced oxidative degradation products Using quantitative NMR (QNMR) to quickly determine the content of crude materials, intermediates, API and synthetic impurities Prepare professional application materials
Method development and method validation
API method development and verification (according to Chinese Pharmacopoeia, American Pharmacopoeia, European Pharmacopoeia, ICH and other requirements and other special requirements of customers) Development and verification of residual solvent methods (in accordance with Chinese Pharmacopoeia, American Pharmacopoeia, European Pharmacopoeia, ICH, etc.)
Drug impurity analysis
Drug impurities have become one of the key concerns of domestic and foreign drug regulatory agencies due to their potential impact on drug quality, safety and effectiveness. With the expansion of the export scale of my country’s pharmaceutical products, understanding the requirements of drug impurity control in foreign regulatory markets and strengthening the analysis and control of drug impurities have become a topic of common concern for domestic pharmaceutical manufacturers.
Any substance that affects the purity of a drug is collectively called an impurity. The Registration Technology for Human Drugs requires the International Harmonization Council (ICH) to define an impurity as any component that exists in a drug and whose chemical structure is inconsistent with the drug. The impurities contained in the medicine will reduce the curative effect, affect the stability of the medicine, and some may even be harmful to human health or produce other toxic and side effects. Therefore, testing related substances and controlling purity are very important to ensure the safety and effectiveness of medication and to ensure the quality of medication.
Main types of drug impurities
1. Organic impurities
Raw materials or pharmaceutical preparations may produce impurities during production or storage. They may be known, unknown, volatile or non-volatile compounds, and their sources include starting materials, intermediates, by-products, and degradation products. They may also come from racemization or contamination between enantiomers. Impurities generated in all these situations may cause undesirable biological activity.
2. Inorganic (elemental) impurities
Inorganic impurities may come from raw materials, synthetic additives, auxiliary materials and production processes used in the production of pharmaceuticals. Several potentially toxic elements may be naturally present in these components, and these elements must be tested in all drugs. Other components may be added during the production process. Once added, the elemental impurities must be monitored. Sources of inorganic impurities include reagents in the production process (such as ligands, catalysts (such as platinum group element PEG)), metals introduced in other stages of the production process (such as production water and stainless steel reaction vessels), activated carbon and filter materials Elemental impurities.
3. remaining solvent
Residual solvents are volatile organic compounds used or generated during the production of drugs. Many organic reagents used in drug synthesis are toxic or harmful to the environment, and are difficult to remove completely. In addition, the final purification process of most pharmaceutical ingredients includes a crystallization step, which will retain a small amount of organic solvent, which may become harmful impurities or cause drug degradation. ICH, USP and EP all set limits for solvent residues.
Pharmaceutical impurity analysis method
1. Analysis method of organic impurities
The detection methods of organic impurities include chemical methods, spectroscopy, chromatography, etc., and different detection methods are used due to different drug structures and degradation products. Separation and detection of impurities with different structures through appropriate analysis techniques to achieve effective control of impurities. With the development and update of separation and detection technology, efficient and fast separation technology is combined with sensitive, stable, accurate and applicable detection methods, almost all organic impurities can be well separated and detected under suitable conditions . In the quality standards, the commonly used impurity detection methods are mainly high performance liquid chromatography (High Performance Liquid Chromatography; HPLC), thin layer chromatography (ThinLayerChromatography; TLC), gas chromatography (Gas Chromatography; GC) and capillary electrolysis
Swimming method (Capillary Electrophoresis; CE).
2. Analysis method of inorganic impurities
The production of inorganic impurities is mainly related to the production process. Since many inorganic impurities directly affect the stability of the drug and can reflect the status of the manufacturing process itself, understanding the status of the inorganic impurities in the drug is of great significance for evaluating the status of the drug manufacturing process. For inorganic impurities, the pharmacopoeias of various countries include classic, simple and effective detection methods. For imitation of mature production technology, quality inspection and control can be carried out by the method of pharmacopoeia according to the actual situation. For new drugs produced by new production processes, ion chromatography and inductively coupled plasma emission spectrometry-mass spectrometry (ICP-MS) and other analytical techniques are encouraged to qualitatively and quantitatively analyze various types of inorganic impurities that may exist in the product in order to The production process is evaluated reasonably and provides a basis for formulating reasonable quality standards.