RESUMO
Icatibant is a peptidomimetic drug serving as a bradykinin-receptor antagonist and is approved in Europe and the United States for the treatment of hereditary angioedema attacks. We have detected an impurity with a high structural similarity to icatibant in pharmaceutical dosage forms using an optimized chromatographic method based on reversed phase high performance liquid chromatography with UV detection. The abundance of the impurity was around 1% relative to the icatibant peak following storage at room temperature for 1â¯month, and raised up to ~16% upon temperature stressing at 100⯰C. The impurity was isolated by fraction collection and further purified by solid phase extraction for structural identification. NMR and high resolution mass spectrometric analyses revealed that this impurity results from isomerization in the N-terminal single amino acid residue. The new impurity may warrant particular attention due to its exceptional similarity to the active ingredient icatibant.
Assuntos
Antagonistas de Receptor B2 da Bradicinina/química , Bradicinina/análogos & derivados , Contaminação de Medicamentos , Bradicinina/química , Bradicinina/normas , Antagonistas de Receptor B2 da Bradicinina/normas , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Estrutura Molecular , EstereoisomerismoRESUMO
A method of chiral amino acid analysis versus standard is presented. By treating the peptide sample and a chiral standard whose intrinsic chiral composition is known in the same way, i.e. simultaneous hydrolysation and analysis, exact corrections can be made for the sequence-related and many hydrolysation-related racemisations. The accuracy obtained in this way permits use of the results for quality control of the chiral purity of peptide drugs. Using the bradykinin antagonist Icatibant acetate (INNM) the method was validated with respect to its precision, accuracy, specificity, limit of detection, and robustness.