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-flig ht mass spectra (MALDI-TOFMS) are reported for a series of diamminopla tinum(II) oligodeoxyribonucleotides that represent the known binding m odes 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 MA LDI mass spectra. Sensitivity for detection of the intact complexes un der all MALDI regimes was excellent even in the low picomole range, a value that represents a hundred- to thousand-fold improvement over FAB MS sensitivity. Mono- and diammine losses were observed in all but the positive-ion IR-MALDI mass spectra, their peak abundances being compo und-, wavelength, laser irradiation- and matrix-dependent. Loss of the Pt(NH3)2 group was favored in negative-ion MALDI mass spectra recorde d with sinapinic acid matrix (but not with 30-hydroxypicolinic acid ma trix) and occurred with very low efficiency in the negative-ion IR-MAL DI spectra. Various other prompt fragmentations resulted in low abunda nce peaks in each of the modes. MALDI-TOFMS should be an excellent too l for detection of platinated DNA fragments in biological fluids and e xtracts, providing both molecular weight and limited structural inform ation. Some control over the degree of fragmentation can be imposed by judicious choice of laser wavelength and matrix.