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Toward high-throughput monitoring of metallodrug-protein interaction using capillary electrophoresis in chemically modified capillaries
Authors:Shmykov Alexei Y  Filippov Vladimir N  Foteeva Lidia S  Keppler Bernhard K  Timerbaev Andrei R
Affiliation:a Institute of Analytical Instrumentation, Russian Academy of Sciences, 190103 St. Petersburg, Russia
b Vernadsky Institute of Geochemistry and Analytical Chemistry, Russian Academy of Sciences, 119991 Moscow, Russia
c Institute of Inorganic Chemistry, University of Vienna, A-1090 Vienna, Austria
Abstract:The performance of capillary electrophoresis (CE) operating with a sulfonated capillary for the separation of protein adducts of anticancer ruthenium(III)-based drugs was evaluated. The coated capillary was shown to yield improved resolution of albumin- and transferrin-bound species of ruthenium compared with that attained with the bare fused-silica capillary. The coating also showed an increased reproducibility of migration times and peak areas and allowed reasonably high efficiency separation of analytes (up to 1300 theoretical plates per meter), which display high affinity toward a fused-silica surface. In addition, due to rather high electroosmotic flow (EOF, > 45 × 10−5 cm2 V−1 s−1) in the coated capillary, it enabled fast counter-EOF monitoring of albumin and transferrin adducts. This benefit, together with requiring only a short flush with the background electrolyte to have migration times reproducible (at < 1.5% relative standard deviation), makes this wall-modified capillary holding promise for CE examination of fast reactions such as those accompanying protein-drug interactions and biotransformations associated with drug delivery via protein binding.
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