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Issue 6, 2010
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On-line fast column switching SEC × IC separation combined with ICP-MS detection for mapping metallodrug–biomolecule interaction

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Abstract

Comprehensive fast column switching two-dimensional chromatography has been combined for the first time with ICP-MS detection. The developed, fully automated on-line 2-D system was designed for intact protein separation. Absolute detection limits in the pmol-range were obtained for proteins considering the hetero-elemental tag sulfur, which was detected as SO+ employing dynamic reaction cell technique. The method was implemented for screening the interaction of metallodrugs with proteins in biological samples, which play a key role in the preclinical and clinical drug development. As a key advance, this tool-set is capable of handling any candidate metallodrug. Since covalent and non-covalent interactions are essential in this context, a native orthogonal separation was a prerequisite. Hence, the first dimension involved a size-selective separation, which was followed on-line by ion exchange chromatography employing two parallel monolithic discs. The cycle time of the ion exchange using these disks was 3 min. Hence, while gradient elution of one monolithic disk was performed within 3 min, the second disk was loaded with the next fraction of the size exclusion column. In a feasibility study, cisplatin was studied in serum samples (ex vivo incubation) demonstrating the potential of the method in preclinical studies on candidate drugs.

Graphical abstract: On-line fast column switching SEC × IC separation combined with ICP-MS detection for mapping metallodrug–biomolecule interaction

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Article information


Submitted
08 Jan 2010
Accepted
09 Mar 2010
First published
30 Mar 2010

J. Anal. At. Spectrom., 2010,25, 861-866
Article type
Paper

On-line fast column switching SEC × IC separation combined with ICP-MS detection for mapping metallodrug–biomolecule interaction

S. Hann, T. Falta, K. Boeck, M. Sulyok and G. Koellensperger, J. Anal. At. Spectrom., 2010, 25, 861
DOI: 10.1039/C000427H

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