AQbD approach for the development of an analytical procedure for the separation of cephalosporin drugs and their degradation products

Abstract

In the pharmaceutical industry, analytical procedures are used to conduct research, development and quality control of drugs and medicines. Given the importance of the Analytical Quality by Design (AQbD) approach in the rational development of analytical procedures, especially by minimizing the need for experiments, acquiring and improving knowledge during development and ensuring the flexibility of the method, this study aimed to develop an analytical procedure, based on AQbD principles, for the identification and quantification of different cephalosporins, as well as to create a tool for defining the method operable design region. The initial screening phase of analytical development was carried out using an in silico tool developed in a previous study. During the analytical development phase, a forced degradation study was performed using Liquid Chromatography Coupled to Mass Spectrometry (LC-MS) to identify cephalosporin degradation products. The developed method, along with its Method Operable Design Region (MODR), was validated, resulting in a robust and flexible analytical procedure for identifying and quantifying different cephalosporins in accordance with AQbD principles. The proposed tool considers multiple chromatographic responses, target uncertainty and desired confidence level, simplifying the verification of compliance with quality requirements defined in Analytical Target Profile, offering a reliable process that adapts to parameter changes, maintaining the quality of results.