Enhancing analytical development in the pharmaceutical industry: A DoE-QSRR model for virtual Method Operable Design Region assessment.

Recently, the pharmaceutical industry has increasingly adopted the Analytical Quality by Design (AQbD) approach for analytical development. To facilitate AQbD approach implementation in the development of chromatographic methods for determining cephalosporin antibiotics, an in silico tool capable of performing virtual DoEs was developed enabling to obtain virtual operable regions of method. To this end, the drugs cephalexin, cefazolin, cefotaxime and ceftriaxone were analyzed using four experimental designs, deriving a DoE-QSRR model and employing Monte Carlo method. The DoE-QSRR model and virtual DoEs were validated using data not used in model's construction, obtaining coefficients of determination of 84.72 % for DoE-QSRR model and over 77 % for virtual DoEs. Virtual MODRs were constructed using data from the virtual DoEs. The virtual MODRs were validated by comparing them with experimental MODRs under various scenarios, with overlap areas reaching values exceeding 84 %. Therefore, the in silico tool was considered suitable for indicating analyte trends under different analytical conditions, being capable of performing virtual DoEs for cephalosporin drugs with sufficient assertiveness to guide analytical development and allow obtaining a MODR capable of providing results of adequate quality.