Pharmaceuticals impurity profiling

Since the final product is a pharmaceutical, high purity of the product is definitely required. Furthermore, the amount of any impurities in the final product has to be rigorously regulated under ICH guidelines. Rejection of impurities related to cyclopropylacetylene (37) was difficult throughout this whole process [28]. Thus, not only the isolated yield but the impurity profile of 37 was critical. 

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. 

VIII. IMPURITY PROFILING FOR DRUG SUBSTANCES AND PHARMACEUTICAL PRODUCTS... 

After a short introduction into the relevance of Impurity profiling for regulatory authorities, public health, and the pharmaceutical industry, an overview is presented based on the various modes of capillary electrophoresis that have been used in drug impurity analysis. The applications of capillary zone electrophoresis, non-aqueous capillary electrophoresis, micellar electrokinetic capillary chromatography, microemulsion electrokinetic capillary chromatography, capillary gel electrophoresis, and capillary electrochromatography are presented consecutively. 

CEC provided repeatable separation of isradepin and its six by-products within 1.6 min on a 143 mm column packed with 3 pm Cig. CEC was found to be more selective compared to MEKC for the impurity profiling of pharmaceutical compounds such as fluticasone propionate and cefuroxime axetil. With a homemade column packed with 3 pm... 

Visky, D., Jimidar, I., Van Ael, W., Vennekens, T., Redlich, D., and De Smet, M. (2005). Capillary electrophoresis-mass spectrometry in impurity profiling of pharmaceutical products. Electrophoresis 26, 1541-1549. 

From 1993 to the present, several publications have described anion and cation analysis for determination of pharmaceutical counterions (Pigure 16). and impurity profiling. For these applications, several buffers were used on different CE instruments. In most cases, detection was indirect or direct UV detection for analytes such as bromide that do absorb at 200 nm. Two papers describe use of a conductivity detector. 

Pluym et al. compared the use of CE to that of HPLC in chemical and pharmaceutical quality control. They stated that CE could be considered as a complementary technique to HPLC because of its large separation capacity, its simplicity, and its economical benefits. Jimidar et al. decided that CE offers high separation efficiency and can be applied as an adjunct in HPLC method validation. Mol et al. evaluated the use of micellar electrokinetic chromatography (MEKC) coupled with electrospray ionization mass spectrometry (ESI—MS) in impurity profiling of drugs, which resulted in efficient separations. 

CEC has found wide pharmaceutical applications including impurity profiling and analyses of pharmaceuticals in biofluids, in proteomics and genomics, and in the food industry... 

Much of the knowledge needed for manufacturing a pharmaceutical is related to the last step in the process, including understanding the bulk active ingredient, its impurity profile, chiral purity, and crystal form. To cut down the entire scale-... 

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