DETERMINATION OF IFOSFAMIDE BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY

Ifosfamide, an oxazaphosphorine, is thermally stable during elution in gas chromatography (GC) at temperatures above 200-degrees-C, in contrast to its structural isomer cyclophosphamide. Both 2.65-mu-m and 0.32-mu-m OV-1 columns were efficient for GC of ifosfamide without derivatization. Mass spectrometry (MS), showed that intact ifosfamide was eluted without interference from naturally occurring metabolites in blood plasma. Ifosfamide can be monitored, by capillary GC-MS without derivatization, in blood plasma from cancer patients treated with the drug. Only a liquid-liquid extraction is required before injection of the sample. A single peak of ifosfamide is detected with molecular mass 260; fragmentation starts with loss of CH2Cl ([M - CH2Cl], m/z 211). The limit of determination for ifosfamide in human plasma was about 50 nM (10 ng ml-1). Recovery, quality of calibration curves and reproducibility were suitable for the rapid determination of ifosfamide in the range 0.01 - 1000-mu-g ml-1.