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  • Title: Bioanalysis of therapeutic peptides: differentiating between total and anti-drug antibody bound drug using liquid chromatography-tandem mass spectrometry quantitation.
    Author: Heinig K, Wirz T, Schick E, Guenzi A.
    Journal: J Chromatogr A; 2013 Nov 05; 1316():69-77. PubMed ID: 24119751.
    Abstract:
    An acylated peptide with MW ~4.5 kDa was measured in samples from pharmacokinetic, toxicology and clinical studies using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Lower limits of quantitation of 2 ng/mL and 50 pg/mL were achieved for animal and human plasma, respectively. Repeated drug administration may lead to anti-drug antibodies (ADA) which can inactivate the drug by formation of drug-ADA complexes. Hence, the LC-MS/MS assay incorporated cleavage of potential drug-ADA complexes to quantify the total plasma concentration. To obtain information on active drug levels, an assay that measures the free concentration or alternatively the ADA-unbound concentration would be needed. Ultrafiltration experiments through 100 kD cutoff membranes to remove Ig-bound peptide were not successful due to nonspecific binding. Extraction of Ig-bound drug using Protein A or G (bacterial cell wall proteins with high affinity to the Fc region of IgG) was suitable to distinguish between ADA-bound drug and [free+protein bound (not ADA-bound)] drug and correlated with findings from ELISA ADA measurement.
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