Feasibility of HPLC/CRIMS to determine pharmacokinetics and metabolism of stable-isotope labeled therapeutic proteins.

摘要

The expansion in use of proteins and other macromolecules as pharmaceutical agents over the last decade drives the search for better analytical techniques to perform pharmacokinetic and metabolism studies. This study evaluates the feasibility of using a fully stable-isotope labeled protein and a novel analytical strategy, chemical reaction interface mass spectrometry (CRIMS), to perform such studies.;In CRIMS, an analyte eluting from a chromatographic column enters a zone where it is completely dissociated by a microwave-induced helium plasma. The dissociated analyte atoms then interact with a reactant gas (SO;Uniformly labeled ;GH;The study shows that conducting pharmacokinetic studies using fully labeled proteins and analysis by HPLC/CRIMS is feasible. Using nonradioactive isotope labeling makes the method safe. The labeled molecules can be distinguished from their endogenous unlabeled counterparts. With uniform labeling, circulating metabolites will be detectable and distinguishable from the parent compound.