Solvent-sample interactions in thermospray mass spectrometry of antineoplastic nitrogen mustards

Conditions are reported for the optimization of thermospray mass spectrometric analysis of antineoplastic nitrogen mustard alkylating agents. In aqueous ammonium acetate mobile phase, multiple sequential solvolytic reactions occur with these highly labile compounds, and protonated molecular ions of the reaction products are observed. However, when high proportions of acetonitrile or other organic modifier are added to the mobile phase, solvolytic reactions are much reduced and abundant protonated molecular ions are detected. One exception to these observations is phosphoramide mustard, which solvolyses under all conditions attempted. A lower limit for detection of melphalan using direct injection and summing the ion current between m/z 120 and 870 is about 150 ng. Successful thermospray liquid chromatography/mass spectrometry of these compounds should be possible using high percentages of methanol in the mobile phase or increasing the organic content by post-column solvent modification.