Elucidation of peptide metabolism by on-line immunoaffinity liquid chromatography mass spectrometry

An immunoaffinity chromatography extraction capillary liquid chromatography separation has been coupled to electrospray ionization mass spectrometry f or on-line characterization of drug metabolites of a therapeutic peptide in plasma. It is demonstrated that the selectivity, sensitivity and molecular weight data provided by immunoaffinity chromatography coupled to liquid ch romatography/mass spectrometry provides a means of rapidly achieving qualit ative determinations of small amounts of material in complicated biological matrices such as plasma. The ability to detect the peptide in rat plasma a t a level of 10 ng/mL is demonstrated using this method. In addition, exper iments to study the epitope of the peptide by enzymatic digestion and mass spectrometry are also discussed, The method is proposed as an alternative a pproach to studying the metabolism of therapeutic peptides, Copyright (C) 2 000 John Wiley & Sons, Ltd.