title: Polymorphism in cisplatin anticancer drug.
abstract: This study reports a combined experimental and theoretical study of the solid-state polymorphism of the anticancer agent cisplatin. A complete assignment was performed for the inelastic neutron scattering (INS) and Raman spectra collected simultaneously for cisplatin, at different temperatures, with a view to obtain reliable and definitive evidence of the relative thermal stability of its α and β polymorphic species. A marked temperature-dependent hysteresis was observed, as previously reported in the literature. Theoretical calculations were carried out at the density functional theory level, using a plane-wave basis set approach and pseudopotentials. A detailed comparison with the experimental Raman and INS data showed that the α polymorph is present at the lowest temperatures, whereas the β form occurs near room temperature. Furthermore, regions of coexistence of both forms are identified, which depend on the working mode (heating or cooling). These findings imply that Raman spectroscopy allows clear identification of the α and β polymorphs at a given temperature and can unambiguously discriminate between them. Elucidation of the polymorphic equilibrium of this widely used anticancer drug is paramount for its pharmaceutical preparation and storage conditions.
authors: Research Unit Molecular Physical Chemistry, Faculty of Science and Technology, University of Coimbra, 3004-535 Coimbra, Portugal. pmc@ci.uc.pt
authors: M Paula M
authors: MP
authors: Marques
authors: Rosendo
authors: R
authors: Valero
authors: Stewart F
authors: SF
authors: Parker
authors: John
authors: J
authors: Tomkinson
authors: Luís A E
authors: LA
authors: Batista de Carvalho
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002945:Cisplatin / Q000737:chemistry*; D008958:Models, Molecular; D013059:Spectrum Analysis, Raman; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin