Advances of CE-ICP-MS in speciation analysis related to metalloproteomics of anticancer drugs

The mode of action of metal-based anticancer drugs, including their accumulation in blood, transport, delivery to cancer cell, and cell processing (together with release of an active form and possibly targeting) is largely dependent on protein binding. Among analytical methods capable of providing a better understanding of metallodrug–protein interactions, capillary electrophoresis (CE) with inductively coupled plasma mass spectrometry (ICP-MS) detection is arguably a premier technique. Since its advent to the area of metallodrug proteomics in 2004 [1], the benefits of CE-ICP-MS became evident, stimulating further research and methodological developments. This hyphenated technique's merits comprise an ability to separate rapidly and efficiently the parent drug and protein-bound drug form(s), with no alteration of original speciation in the sample, to identify the metal-containing species due to specific ICP-MS response, to measure the binding parameters (e.g. rate and equilibrium constants), and finally to quantify the metal–protein adducts in real-world samples. This review is aimed on offering the reader a summary of applications of CE-ICP-MS to various metallodrug–protein systems, with a focus on experimental strategies in use for the assessment of binding reactivity and affinity, monitoring in vitro cellular transformations and serum binding profiles, and ex vivo metallodrug–proteomic analysis.