Impurity profile development

Impurity testing is pivotal in pharmaceutical development for establishing drug safety and quality. In this chapter, an overview of impnrity evaluations of drug substances and products by HPLC is presented from both the laboratory and regulatory standpoints. Concepts from the development of impurity profiles to the final establishment of public specifications are described. Useful strategies in the identification and quantification of impurities and degradation products are summarized with practical examples to illustrate impurity method development. 

The development of an impurity profile for a dosage form follows many of the same principles as in the drug substances however, instead of identifying all precursors and intermediates, the analyst will identify and place all of the components of the dosage form (excipients, preservatives, and others) and their affiliated impurity profiles within a master profile. Here again additional method development may be needed to... 

During the course of chemical development, impurity profiles in drug substances may change due to changes in synthetic route and changes in the size of the batch. ICH guidelines for Impurities in New Drug Substances (ICH Q3A), require that impurity test results for... 

Various international pharmacopoeias help assure the quality of drugs worldwide. These pharmacopoeias constantly review and revise their monographs. A different impurity profile can be anticipated if a drug s production process is changed this results in the development of new analytical methods that need to be incorporated in the pharmacopoeias. In earlier editions, color reactions were performed for identification and purity evaluation purposes. 

Hammitzsch, M., Rao, R. N., and Scriba, G. K. E. (2006). Development and validation of a robust capillary electrophoresis method for impurity profiling of etomidate including the determination of chiral purity using a dual cyclodextrin system. Electrophoresis 27(21), 4334—4344. 

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