Comparability analysis of protein therapeutics by bottom-up LC-MS with stable isotope-tagged reference standards.

ABSTRACT: Comparability studies lie at the heart of assessments that evaluate differences amongst manufacturing processes and stability studies of protein therapeutics. Low resolution chromatographic and electrophoretic methods facilitate quantitation, but do not always yield detailed insight into the effect of the manufacturing change or environmental stress. Conversely, mass spectrometry (MS) can provide high resolution information on the molecule, but conventional methods are not very quantitative. This gap can be reconciled by use of a stable isotope-tagged reference standard (SITRS), a version of the analyte protein that is uniformly labeled (13)C6-arginine and (13)C6-lysine. The SITRS serves as an internal control that is trypsin-digested and analyzed by liquid chromatography (LC)-MS with the

SUBMITTER: Manuilov AV 

PROVIDER: S-EPMC3218535 | biostudies-literature | 2011 Jul-Aug

REPOSITORIES: biostudies-literature