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Qualitative and quantitative investigations of cyclophosphamide (NSC-26271), cyclophosphamide metabolites, and related compounds by field-desorption mass spectrometry.

The potential of field-desorption mass spectrometry (FD-MS) coupled with photoplate detection for qualitative and quantitative studies on cyclophosphamide (CP) and its metabolites is reviewed. The characteristic features of this ionization mode are minimal fragmentation of the molecular ion coupled with the capacity to produce such ions from thermally unstable or nonvolatile samples. Since CP is itself extensively fragmented in the electron-impact ionization mode, and since it possesses both thermally unstable (eg, 4-hydroxycyclophosphamide, carboxyphosphamide) as well as ionic and hence nonvolatile metabolites (eg, phosphorodiamidic acid), the FD technique has potential value for the detection and quantitation of the drug and its metabolites in underviatized mixtures. Some of the factors which influence the reproducibility of FD spectra are enumerated. In order to improve the FD technique for quantitative results a device for emission-controlled FD was constructed and its use is described. Three different modes of operation are discussed using the FD spectra of CP conjugates typical for each. Preliminary investigations into the use of the d6 analog of CP for quantitation of the drug by FD-MS are also reported.