MATRIX-ASSISTED UV AND IR LASER-DESORPTION IONIZATION TIME-OF-FLIGHT MASS-SPECTROMETRY OF DIAMMINOPLATINUM(II) OLIGODEOXYRIBONUCLEOTIDE ADDUCTS AND THEIR UNPLATINATED ANALOGS

The matrix-assisted UV and IR laser desorption-ionization time-of-flight mass spectra (MALDI-TOFMS) are reported for a series of diamminoplatinum(II) oligodeoxyribonucleotides that represent the known binding modes of the antitumor drug cisplatin [cis-diamminedichloroplatinum(II)] to DNA. Within the set of experimental conditions investigated, the best overall signal-to-noise ratio was obtained for negative-ion IR MALDI mass spectra. Sensitivity for detection of the intact complexes under all MALDI regimes was excellent even in the low picomole range, a value that represents a hundred- to thousand-fold improvement over FABMS sensitivity. Mono- and diammine losses were observed in all but the positive-ion IR-MALDI mass spectra, their peak abundances being compound-, wavelength, laser irradiation- and matrix-dependent. Loss of the Pt(NH3)2 group was favored in negative-ion MALDI mass spectra recorded with sinapinic acid matrix (but not with 30-hydroxypicolinic acid matrix) and occurred with very low efficiency in the negative-ion IR-MALDI spectra. Various other prompt fragmentations resulted in low abundance peaks in each of the modes. MALDI-TOFMS should be an excellent tool for detection of platinated DNA fragments in biological fluids and extracts, providing both molecular weight and limited structural information. Some control over the degree of fragmentation can be imposed by judicious choice of laser wavelength and matrix.