P-120-R: Absolute Quantifications of Problematic CHO Lipases by PRM-MS - Case Studies

Presence of host cell-derived lipases in biologic drug substances has been linked to polysorbate degradation, which can compromise drug stability, shorten shelf life, and lead to costly manufacturing deviations or regulatory concerns. While untargeted Liquid Chromatography-Mass Spectrometry (LC-MS) permits the identification of such host cell proteins (HCPs) with high precision, quantitative data is often inaccurate. Here, we present a parallel reaction monitoring (PRM) assay for highly sensitive lipase identification and quantification using stable isotope labeled (SIL) peptides. Assay qualification with synthetic, unlabeled (UL) peptides demonstrates assay parameters, while a case study with two unique drug substance (DS) samples demonstrates how the CHO 6x Lipase (C6XL) MS Assay enables manufacturers to better assess drug substance quality. Contributing Authors: Johanna Barnhill, Timothy Licknack, Stephen Stahlschmidt, Brinkley Thornton, Jared Isaac Cygnus Technologies, Leland, United States