Journal
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
Volume 1032, Issue -, Pages 119-130Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jchromb.2016.04.040
Keywords
Antibody-drug conjugate; Ado-trastuzumab emtansine; Two-dimensional liquid chromatography; Multiple heart-cutting; Comprehensive
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Antibody-drug conjugates might be the magic bullets referred to by Paul Ehrlich over 100 years ago. Together with a huge therapeutic potential, these molecules come with a structural Complexity that drives state-of-the-art chromatography and mass spectrometry to its limits. The use of multiple heart-cutting (mLC-LC) and comprehensive (LC x LC) multidimensional LC in combination with high resolution mass spectrometry for the characterization of the lysine conjugated antibody-drug conjugate ado-trastuzumab emtansine, commercialized as Kadcyla, is presented. By combining protein and peptide measurements, attributes such as drug loading, drug distribution and drug conjugation sites can be assessed in an elegant manner. (C) 2016 Elsevier B.V. All rights reserved.
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