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Clinical pharmacokinetic assessment of an anti-MAdCAM monoclonal antibody therapeutic by LC-MS/MS
- Source :
- Analytical chemistry. 84(14)
- Publication Year :
- 2012
-
Abstract
- Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been shown to be a viable tool for preclinical pharmacokinetic (PK) analysis of monoclonal antibody (mAb) therapeutics. This work describes free and total PK assays for the mAb PF-00547,659 in serum of ulcerative colitis patients in a First-In-Human study [Vermeire, S. et al. Gut2011, 60 (8), 1068-1075]. The assay to measure free PF-00547,659 used immuno-enrichment with a biotinylated anti-idiotypic antibody and streptavidin magnetic beads. The total assay used enrichment by protein G magnetic beads. Following elution of PF-00547,659 from the beads, addition of an extended sequence stable isotope labeled peptide and trypsin digestion, a proteotypic peptide derived from the CDR region of the light chain of PF-00547,659 was quantified by LC-MS/MS. The free assay had a calibration range from 7.03 ng/mL to 450 ng/mL. The assay was precise and accurate with interbatch imprecision16.5%, and interbatch inaccuracy13.7% at all concentrations investigated during assay qualification. Results from LC-MS/MS methodologies are compared with historical immunoassay data originally acquired during the course of the clinical study. PK parameter estimates were highly correlated between the two analytical approaches. This work provides precedence that immunoaffinity LC-MS/MS can effectively be used to measure the serum concentrations of mAb therapeutics in clinical studies.
- Subjects :
- chemistry.chemical_classification
Streptavidin
Immunoassay
Chromatography
medicine.diagnostic_test
biology
medicine.drug_class
Chemistry
Antibodies, Monoclonal
Peptide
Monoclonal antibody
Molecular biology
Analytical Chemistry
chemistry.chemical_compound
Mucoproteins
Pharmacokinetics
Liquid chromatography–mass spectrometry
Tandem Mass Spectrometry
Biotinylation
medicine
biology.protein
Humans
Protein G
Chromatography, Liquid
Subjects
Details
- ISSN :
- 15206882
- Volume :
- 84
- Issue :
- 14
- Database :
- OpenAIRE
- Journal :
- Analytical chemistry
- Accession number :
- edsair.doi.dedup.....42ae39ab1a69abf7e1249a28aa62e143