A method for studies on interactions between a gold-based drug and plasma proteins based on capillary electrophoresis with inductively coupled plasma mass spectrometry detection.
An analytical method based on capillary electrophoresis (CE) and inductively coupled plasma mass spectrometry (ICP-MS) detection was developed for studies on the interaction of gold-containing drugs and plasma proteins using auranofin as example. A detection limit of 18 ng/mL of auranofin corresponding to 5.2 ng/mL Au and a precision of 1.5 % were obtained. Kinetic studies of the interaction between auranofin and protein were performed by incubation in aqueous solutions as well as 20 % human plasma at 37 °C. The reaction of auranofin with human serum albumin (HSA) and plasma proceeded fast; 50 % of un-bound auranofin disappeared within 2 and 3 min, respectively. By blocking the free cysteine (Cys-34) by iodoacetamide on HSA, it was shown that Cys-34 was the main reaction site for auranofin. By selective labeling of HSA present in 20 % human plasma with iophenoxate, it was demonstrated that HSA was the major auranofin-interacting protein in plasma. The CE-ICP-MS method is proposed as a novel approach for kinetic studies of the interactions between gold-based drugs and plasma proteins. Graphical Abstract Development of a CE-ICP-MS based method allows for studies on interaction of the gold containing drug auranofin with plasma proteins.
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
Tam T T N
TT
Nguyen
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.
Jesper
J
Østergaard
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark. bente.gammelgaard@sund.ku.dk.
Bente
B
Gammelgaard
D018501:Antirheumatic Agents / Q000097:blood* / Q000737:chemistry; D001310:Auranofin / Q000097:blood* / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D019075:Electrophoresis, Capillary / Q000379:methods*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007460:Iodoacetamide / Q000737:chemistry; D007480:Iopanoic Acid / Q000737:chemistry; D007700:Kinetics; D057230:Limit of Detection; D012709:Serum Albumin / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D013054:Spectrophotometry, Atomic / Q000379:methods*; D013194:Staining and Labeling / Q000379:methods
D018501:Antirheumatic Agents; D012709:Serum Albumin; D001310:Auranofin; C008160:iophenoxic acid; D006046:Gold; D007480:Iopanoic Acid; D003545:Cysteine; D007460:Iodoacetamide
Albumin; Auranofin; CE-ICP-MS; HSA; Human plasma; Iophenoxate