title: A study of the interactions between carboplatin and blood plasma proteins using size exclusion chromatography coupled to inductively coupled plasma mass spectrometry.
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 gamma-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 gamma-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 gamma-globulin was 1.01 M(-1) min(-1), which are both lower than the rate constant of the cisplatin-albumin reaction previously reported.
authors.affiliation: Environmental and Occupational Health Sciences Institute, Rutgers, The State University of New Jersey, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Xie
authors.forename: Willie
authors.initials: W
authors.lastname: Johnson
authors.forename: Lorna
authors.initials: L
authors.lastname: Rodriguez
authors.forename: Murugesan
authors.initials: M
authors.lastname: Gounder
authors.forename: Gene S
authors.initials: GS
authors.lastname: Hall
authors.forename: Brian
authors.initials: B
authors.lastname: Buckley
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism*; D002138:Calibration; D016190:Carboplatin / Q000097:blood*; D002850:Chromatography, Gel / Q000379:methods*; D006801:Humans; D007700:Kinetics; D013058:Mass Spectrometry / Q000379:methods*; D011485:Protein Binding; D012015:Reference Standards
chemical_list: D000970:Antineoplastic Agents; D001798:Blood Proteins; D016190:Carboplatin