A study of the interactions between carboplatin and blood plasma proteins using size exclusion chromatography coupled to inductively coupled plasma mass spectrometry |
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Authors: | Ruimin Xie Willie Johnson Lorna Rodriguez Murugesan Gounder Gene S Hall Brian Buckley |
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Institution: | (1) Environmental and Occupational Health Sciences Institute, Rutgers, The State University of New Jersey, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA;(2) Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, NJ 08854, USA;(3) Department of Obstetrics and Gynecology and Reproductive Sciences, and Division of Gynecologic Oncology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA;(4) The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA |
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Abstract: | To study the carboplatin–protein interaction, a sensitive method using size exclusion chromatography coupled to inductively
coupled plasma mass spectrometry (SEC–ICP–MS) was developed. The complexes formed between plasma proteins and carboplatin
were monitored and identified with this method. Composite blood plasma samples from patients who were undergoing chemotherapy
were analyzed, and carboplatin was found to bind plasma proteins. In addition, blank plasma samples were spiked with carboplatin
and were analyzed as a time course study, and the results confirmed that carboplatin formed complexes with plasma proteins,
primarily albumin and γ-globulin. To further substantiate the study, these two proteins were incubated with carboplatin. The
binding between carboplatin and these proteins was then characterized qualitatively and quantitatively. In addition to a one-to-one
binding of Pt to protein, protein aggregation was observed. The kinetics of the binding process of carboplatin to albumin
and γ-globulin was also studied. The initial reaction rate constant of carboplatin binding to albumin was determined to be
0.74 M−1 min−1, while that for γ-globulin was 1.01 M−1 min−1, which are both lower than the rate constant of the cisplatin–albumin reaction previously reported. |
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Keywords: | Metal speciation Carboplatin Protein complexation SEC– ICP– MS |
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