SEC hyphenated to a multielement-specific detector unravels the degradation pathway of a bimetallic anticancer complex in human plasma
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AbstractThe bimetallic metal complex Titanocref exhibits relevant anticancer activity, but it is unknown if it is stable to reach target tissues intact. To gain insight, a pharmacologically relevant dose was added to human blood plasma and the mixture was incubated at 37ºC. The obtained mixture was analyzed 5 and 60 min later by size-exclusion chromatography hyphenated to an inductively coupled plasma atomic emission spectrometer (SEC-ICP-AES). We simultaneously detected several titanium (Ti), gold (Au) and sulfur (S)-peaks, which corresponded to a Ti degradation product that eluted partially, and a Au degradation product that eluted entirely bound to plasma proteins (both time points). Although ~70% of the intact Titanocref was retained on the column after 60 min, our results allowed us to establish ̶ for the first time ̶ its likely degradation pathway in human plasma at near physiological conditions. These results suggest that ~70% of Titanocref remain in plasma after 60 min, which supports results from a recent in vivo study in which mice were treated with Titanocref and revealed Ti:Au molar ratios in tumors and organs close to 1:1. Thus, our stability studies suggest that the intact drug is able to reach target tissue. Overall, our results exemplify that SEC-ICP-AES enables the execution of intermediate in vitro studies with human plasma in the context of advancing bimetallic metal-based drugs to more costly clinical studies.
CitationSarpong-Kumankomah, S., Contel, M., & Gailer, J. (2020). SEC hyphenated to a multielement-specific detector unravels the degradation pathway of a bimetallic anticancer complex in human plasma. Journal of Chromatography B, 1145, 122093.
InstitutionUniversity of Calgary
The City University of New York
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