Temperature-resolved thermal analysis of cisplatin by means of Li+ ion attachment mass spectrometry

Abstract

Li⁺ ion attachment mass spectrometry (IAMS) was evaluated as an analytical methodology for measurement of the thermally labile, nonvolatile, and insoluble compound cisplatin, which is used as an anticancer agent in the treatment of testicular and ovarian cancers. We aimed to develop an improved method for the mass spectrometric determination of cisplatin, particularly in its molecular ion form. A uniquely designed quadrupole mass spectrometry system along with a Li⁺ ion attachment technique and a direct inlet probe provided cisplatin molecular ions as Li⁺ ion adducts; to our knowledge this is the first reported instance of cisplatin Li⁺ ion adducts. Full-scan spectra were obtained with ∼10 μg samples. Infrared image furnace-ion attachment mass spectrometry (IIF-IAMS) also was used to study the temperature-programmed decomposition of this drug. The slope of the plot of signal intensity versus temperature for cisplatin decomposition from 225 to 249 °C was used to determine an apparent activation energy (E_a) of 38.0 kcal mol⁻¹ for the decomposition of cisplatin. This decomposition parameter is useful for predicting drug stability (shelf life). In this study, we have demonstrated that IAMS can be a valuable technique for the direct mass spectral analysis and kinetic study of d-metal complex platinum anticancer agents.