TY - JOUR
T1 - Two dimensional separation schemes for investigation of the interaction of an anticancer ruthenium(III) compound with plasma proteins
AU - Sulyok, Michael
AU - Hann, Stephan
AU - Hartinger, Christian
AU - Keppler, Bernhard
AU - Stingeder, Gerhard
AU - Köllensperger, Gunda
N1 - DOI: 10.1039/b508060f
Coden: JASPE
Affiliations: Department of Chemistry, BOKU, University of Natural Resources and Applied Life Sciences, Muthgasse 18, 1190 Vienna, Austria; Institute of Inorganic Chemistry - Bioinorganic, Environmental and Radiochemistry, University of Vienna, Waehringer Str. 42, 1090 Vienna, Austria
Adressen: Koellensperger, G.; Department of Chemistry; BOKU; University of Natural Resources and Applied Life Sciences; Muthgasse 18 1190 Vienna, Austria
Source-File: ChemieErgScopus.csv
Import aus Scopus: 2-s2.0-24644497689
Importdatum: 09.01.2007 14:08:25
12.02.2008: Datenanforderung 2112 (Import Sachbearbeiter)
09.02.2010: Datenanforderung UNIVIS-DATEN-DAT.RA-2 (Import Sachbearbeiter)
PY - 2005
Y1 - 2005
N2 - On-line 2-dimensional size exclusion/anion exchange chromatography was coupled to inductively coupled mass spectrometry with dynamic reaction cell technology (SEC-IC-ICP-MS) in order to characterize the interaction of the ruthenium-based anticancer drug KP1019 with human plasma proteins in vitro and, for the first time, in vivo. In SEC-ICP-MS studies the drug was found to bind exclusively to the protein fraction of 60-80 kDa in human plasma samples (clinical study/phase 1). The respective size fraction was collected and subsequently analyzed by reversed phase chromatography coupled to electrospray mass spectrometry (LC-ESI-MS) confirming the presence of the two well known transporter proteins, i.e. human serum albumin (HSA) and transferrin (Tf). Hence, for in vivo investigation of KP1019 interaction with HSA and Tf a fully automated SEC-IC-ICP-MS approach was applied. The stoichiometry of the KP1019 protein binding was determined through the molar Ru/S ratio. Human apo-Tf standards incubated with different stoichiometric equivalents of KP 1019 were used for species-specific and species-unspecific calibration of the molar Ru/S ratio. Competitive in vitro incubation of KP1019 to both HSA and Tf for ca. 10 h showed that
AB - On-line 2-dimensional size exclusion/anion exchange chromatography was coupled to inductively coupled mass spectrometry with dynamic reaction cell technology (SEC-IC-ICP-MS) in order to characterize the interaction of the ruthenium-based anticancer drug KP1019 with human plasma proteins in vitro and, for the first time, in vivo. In SEC-ICP-MS studies the drug was found to bind exclusively to the protein fraction of 60-80 kDa in human plasma samples (clinical study/phase 1). The respective size fraction was collected and subsequently analyzed by reversed phase chromatography coupled to electrospray mass spectrometry (LC-ESI-MS) confirming the presence of the two well known transporter proteins, i.e. human serum albumin (HSA) and transferrin (Tf). Hence, for in vivo investigation of KP1019 interaction with HSA and Tf a fully automated SEC-IC-ICP-MS approach was applied. The stoichiometry of the KP1019 protein binding was determined through the molar Ru/S ratio. Human apo-Tf standards incubated with different stoichiometric equivalents of KP 1019 were used for species-specific and species-unspecific calibration of the molar Ru/S ratio. Competitive in vitro incubation of KP1019 to both HSA and Tf for ca. 10 h showed that
M3 - Article
SN - 0267-9477
VL - 20
SP - 856
EP - 863
JO - Journal of Analytical Atomic Spectrometry
JF - Journal of Analytical Atomic Spectrometry
IS - 9
ER -