Impurities and Reference Standards

Importance of Impurity and Reference Standards

Impurity and reference standards are essential chemicals in food, pharmaceutical, and nutraceutical industries as the quality of edible things is of prime importance, especially pharmaceuticals. Impurity standards are used as references for the identification and quantification of impurities in pharmaceutical and other chemical products. Matching with reference standards is crucial for establishing test product specifications, validating analytical methods, and ensuring the safety, efficacy, and quality of test products/samples such as pharmaceutical intermediates or drugs.

Custom Synthesis of Impurity and Reference Standards

Researchers and manufacturers generally rely on commercially available standards for identification and synthetic purposes. However, sometimes some specific standards of interest might not be available in desired purity or quantity or are not available at all. Such situations call for specialized synthesis of required compounds, which can be fulfilled by custom synthesis of the compounds of interest with required purity and yield. Custom synthesis of unique impurities needs to be carried out in case of new drug substances or new chemical research. Custom synthesis is the process of producing impurity standard materials in a specific way via a meticulously planned synthetic pathway. By filling in the gaps left by commercially available standards, this approach guarantees the generation of reference substances that precisely represent the impurities of interest.

Stages in Impurity and Reference Standard Custom Synthesis

·       Impurity Identification and Characterization: Impurities present in the substance of interest are isolated and identified. Here characterization and structural elucidation of impurities is carried out using advanced analytical techniques such as mass spectrometry, nuclear magnetic resonance spectroscopy, and chromatographic methods.

·       Route Selection and Design: An appropriate synthetic route and strategy for the synthesis of standards are devised considering the scalability, efficiency, and availability of starting materials during route selection. The chosen synthetic strategy ensures the synthesis of impurity standard material with sufficient purity and quantity.

·       Synthesis and Purification: The actual synthesis of the standard chemicals is carried out according to the finalized synthetic route. The procedure involves reactions, purification steps, and isolation techniques to obtain the standards.

·       Analytical Method Development and Validation: After the standard material is synthesized, analytical methods are developed and validated for characterization and quantification of the standards. The methods developed are specific, sensitive, and precise.

Challenges in Impurity and Reference Standard Custom Synthesis

·       Availability of Reference Materials

·       Complexity of Impurity Structures

·       Synthetic Route Optimization

·       Impurity Quantification and Purity Determination