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Reduction of matrix interferences by the combination of chaotropic salt and DMSO in a broadly applicable target-based ELISA for pharmacokinetic studies of therapeutic monoclonal antibodies

Doucet, Julie and Canadi, Jasna and Kalis, Christoph and Valentin, Marie-Anne and Marrony, Severine and Deckert-Salva, Fabienne and Legay, Francois and Avrameas, Alexandre (2009) Reduction of matrix interferences by the combination of chaotropic salt and DMSO in a broadly applicable target-based ELISA for pharmacokinetic studies of therapeutic monoclonal antibodies. Journal of Pharmaceutical and Biomedical Analysis, 50 (5). pp. 924-931. ISSN 0731-7085

Abstract

Use of a synergistic effect of DMSO together with a chaotropic salt (NaSCN or MgCl2)
allowed to drastically reduce matrix interferences in an ELISA for therapeutic monoclonal
antibodies. Optimum combinations were found to be 0.4 M NaSCN together with 10.0 %
DMSO, and 1.0 M MgCl2 with 15.0 % DMSO. At this optimum combination, quality controls
spiked with mAb at 50.0 ng/ml in eighteen individual human sera and plasmas were
quantified with an overall accuracy of 102.0 %. All of these QCs fulfilled the acceptance
criteria of 80.0 - 120.0 % accuracy and precision below 20.0 %. The assay was also
successfully applied to the quantification of two other mAbs in human serum. Furthermore,
the use of the assay was extended to preclinical species (cynomolgus monkey and rat serum).
Here, the performed validation experiments confirmed the utility of the assay and
demonstrated that the assay allowed quantification of mAb from 50.0 ng/ml to 100.0 μg/ml in
cynomolgus monkey serum. The method has then been applied to a pharmacokinetic study in
cynomolgus monkeys. In summary, this work demonstrates the efficacy of the combination of
a chaotropic salt with DMSO to minimize matrix interferences in an ELISA. The robustness
thus obtained allowed the successful establishment of a cost effective, target-based ELISA
format for use in pharmacokinetic studies, that is easily applicable for the quantification of
mAbs in various matrices such as human, cynomolgus monkey or rat serum and plasma.

Item Type: Article
Related URLs:
Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords: Matrix interferences; ELISA; pharmacokinetic; chaotropic; dimethylsulfoxide
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Date Deposited: 13 Oct 2015 13:17
Last Modified: 13 Oct 2015 13:17
URI: https://oak.novartis.com/id/eprint/1048

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