A Robust Purity Method for Biotherapeutics Using New Peak Detection in an LC–MS-Based Multi-Attribute Method

• DOI: 10.1021/jasms.2c00355
• Publication Date: 2023-02-21T19:33:53Z
• Authors: Monica Sadek; Benjamin Nathan M...; Christopher Yu; Nicholas Ruppe; Austin Abdun-Nabi; Zhiqi Hao; Melissa Alvarez; Sanket Dahotre; Galahad Deperalta
• Keywords: Biological Products; Tandem Mass Spectrometry; 01 natural sciences; Chromatography, Liquid; 0104 chemical sciences

New peak detection (NPD), as part of the LC-MS-based multi-attribute method (MAM), allows for sensitive and unbiased new or changing site-specific attributes between a sample reference that is not possible with conventional UV fluorescence detection-based methods. MAM NPD can serve purity test establish whether are similar. The broad implementation in biopharmaceutical industry has been limited by potential presence false positives artifacts, which increase analysis time trigger unnecessary investigations product quality. Our novel contributions to success curation positives, use known list concept, pairwise approach, development system suitability control strategy. In this report, we also introduce unique experimental design utilizing sequence variant co-mixes measure performance. We show superior performance relative methods an unexpected change compared reference. frontier testing reduces subjectivity, need analyst intervention, missing quality changes.