Quantification of bifunctional diethylenetriaminepentaacetic acid derivative conjugation to monoclonal antibodies by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Anal Biochem. 2007 Sep 15;368(2):214-21. doi: 10.1016/j.ab.2007.06.019. Epub 2007 Jun 17.

Abstract

The results of the characterization of a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry-based method that was developed to establish the stoichiometry of CHX-A''-diethylenetriaminepentaacetic acid (DTPA) or benzyl-DTPA conjugated to a recombinant immunoglobulin G (IgG) are reported. This simple method does not require an accurate measurement of the sample protein concentration to accurately quantify the number of DTPA conjugated. It is also not necessary to thoroughly remove nonconjugated DTPA from the sample. The average number of moles of DTPA attached per mole of IgG was calculated from the difference in the observed masses of DTPA-IgG and nonconjugated IgG divided by the molecular weight of the DTPA derivative. As more DTPA is attached, the [M+H](+) peak of DTPA-IgG becomes broader and noisier. Also, the signal intensity in the mass spectrum decreases, apparently due to the increase in the heterogeneity in the number of DTPA attached to each molecule of IgG. The standard deviation of the measured mass and that of the stoichiometry of the DTPA attached per IgG increased as more DTPA was attached. The standard deviation, expressed as coefficient of variation for samples with 2 to 4 mol of DTPA attached per mole of IgG, was 8 to 9%.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / metabolism
  • Antigens / metabolism
  • Arsenazo III / chemistry
  • Arsenazo III / metabolism
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Enzyme-Linked Immunosorbent Assay
  • Hydrogen-Ion Concentration
  • Immunoglobulin G / genetics
  • Immunoglobulin G / isolation & purification
  • Immunoglobulin G / metabolism
  • Isothiocyanates / chemistry*
  • Pentetic Acid / analogs & derivatives*
  • Pentetic Acid / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*
  • Temperature

Substances

  • Antibodies, Monoclonal
  • Antigens
  • Immunoglobulin G
  • Isothiocyanates
  • Recombinant Proteins
  • benzyl-DTPA
  • N-(2-amino-3-(4-isothiocyanatophenyl)propyl)cyclohexane-1,2-diamine-N,N',N',N'',N''-pentaacetic acid
  • Arsenazo III
  • Pentetic Acid