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Issue 10, 2011
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LC– and CZEICP-MS approaches for the in vivo analysis of the anticancer drug candidate sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (KP1339) in mouse plasma

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Abstract

Ruthenium–indazole complexes are promising anticancer agents undergoing clinical trials. KP1339 is administered intravenously (i.v.), where serum proteins are the first available biological binding partners. In order to gain a better insight into the mode of action, mice were treated with different doses of KP1339i.v. and sacrificed at different time points. The blood plasma was isolated from blood samples and analyzed by capillary zone electrophoresis (CZE) and size exclusion/anion exchange chromatography (SEC-IC) both combined on-line to inductively coupled plasma-mass spectrometry (ICP-MS). The performance of the analytical methodology was compared and the interaction of KP1339 with mouse plasma proteins characterized in vivo. Interestingly, the samples of the mice treated with 50 mg kg−1 and terminated after 24 h showed a ca. 4-fold lowered albumin content and increased ruthenation of albumin aggregates as compared to the untreated control group and the 40 mg kg−1group. The majority of Ru was bound to albumin and the stoichiometry of the KP1339 protein binding was determined through the molar Ru/S ratio. In general, good agreement of the data obtained with both techniques was achieved and the SEC-IC method was found to be more sensitive as compared to the CZE–ICP-MS approach, whereas the latter benefits from the shorter analysis time and lower sample consumption.

Graphical abstract: LC– and CZE–ICP-MS approaches for the in vivo analysis of the anticancer drug candidate sodium trans-[tetrachloridobis(1H-indazole)ruthenate(iii)] (KP1339) in mouse plasma

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Supplementary files

Publication details

The article was received on 18 May 2011, accepted on 01 Sep 2011 and first published on 21 Sep 2011


Article type: Paper
DOI: 10.1039/C1MT00055A
Metallomics, 2011,3, 1049-1055

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    LC– and CZEICP-MS approaches for the in vivo analysis of the anticancer drug candidate sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (KP1339) in mouse plasma

    A. K. Bytzek, K. Boeck, G. Hermann, S. Hann, B. K. Keppler, C. G. Hartinger and G. Koellensperger, Metallomics, 2011, 3, 1049
    DOI: 10.1039/C1MT00055A

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