Application of capillary electrophoresis-inductively coupled plasma mass spectrometry to comparative studying of the reactivity of antitumor ruthenium(III) complexes differing in the nature of counter-ion toward human serum proteins.
Varying the counter-ion is a highly supportive practice in tackling the problem of poor water-solubility of metal complexes of pharmaceutical importance. As a matter of fact, the relevant structural modification may alter the metabolic pathways and possibly the mode of action of a drug. To prove that this does not take place for one of the lead anticancer metal-based developmental compounds, indazolium trans-[RuCl(4)(1H-indazole)(2)] (KP1019), its reactivity toward human serum proteins was assessed under simulated physiological conditions and compared to that of a much more soluble analogue, sodium trans-[RuCl(4)(1H-indazole)(2)] (KP1339). For such kinetic assaying, capillary electrophoresis (CE) interfaced online with inductively coupled plasma mass spectrometry (ICP-MS) to specifically monitor changes in the metal speciation following the formation of ruthenium-protein adducts was applied. The rate constants of interaction with albumin and transferrin were determined at pharmacologically fitting drug-to-protein ratios as on average 0.0319+/-0.0021 min(-1) and 0.0931+/-0.0019 min(-1) (KP1019) and 0.0316+/-0.0018 min(-1) and 0.0935+/-0.0053 min(-1) (KP1339), respectively. The results of this brief study showed that changing from organic to inorganic counter-ion at the stage of formulation could commonly be recommended for improving ruthenium-based drug solubility and bioavailability.
Połeć-Pawlak
Kasia
K
Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland.
Abramski
Jan K
JK
Ferenc
Julia
J
Foteeva
Lidia S
LS
Timerbaev
Andrei R
AR
Keppler
Bernhard K
BK
Jarosz
Maciej
M
D000465:Algorithms; D000970:Antineoplastic Agents / Q000737:chemistry*; D001798:Blood Proteins / Q000737:chemistry*; D053801:Capillary Electrochromatography; D006801:Humans; D007191:Indazoles / Q000737:chemistry; D007202:Indicators and Reagents; D007700:Kinetics; D013058:Mass Spectrometry; D009942:Organometallic Compounds; D017975:Ruthenium Compounds / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry; D012996:Solutions; D014168:Transferrin / Q000737:chemistry
D000970:Antineoplastic Agents; D001798:Blood Proteins; D007191:Indazoles; D007202:Indicators and Reagents; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; D012709:Serum Albumin; D012996:Solutions; D014168:Transferrin; C499292:indazolium trans-(tetrachlorobis(1H-indazole)ruthenate (III))