Analytical Method Transfer of an Active Substance for the Prevention of Nausea and Vomiting Associated with Chemotherapy Sessions

Abstract

This project aimed to transfer an analytical procedure for physical and chemical analysis of an active substance that will be used in a drug product used to prevent vomiting and nausea associated with chemotherapy sessions. Therefore, this crucial step aims to verify that the analytical method developed and validated by the active substance manufacturer provides the same results when performed in different laboratories. This allowed an analytical qualification to confirm the results described by the manufacturer and to ensure that the active substance used in the drug product has the required qualities. All analytical methods considered critical for proving proper use were transferred under the conditions defined by the European Pharmacopoeia and have been validated according to the International Conference on Harmonization (ICH) guidelines. These include: Identification and Assay by HPLC; Related Substances (Tests 1 and 2) by HPLC; Stereochemical Purity by HPLC; Content of acetic acid by HPLC; Residual Solvents by GC; Content of N-methyl D-glucamine by potentiometry and Water content by Karl-Fisher method. The results demonstrated that in the Identification and Assay method, the retention time of the main peak matches to the active substance peak and presented a content of 100.7% w/w. In the Related Substances and Stereochemical Purity tests, all impurities and other isomer were present at levels below 0.15%. All Residual Solvents conferred limits according to specifications. The N-methyl D-glucamine content on anhydrous basis was 37.4% and Water Content 2.09%. The parameters evaluated in the analytical transfer, such as specificity, linearity, precision (system and method repeatability), accuracy and quantitation limit met the defined acceptance criteria and, therefore, the analytical method developed by the API manufacturer was considered successfully transferred.