Determination of ifosfamide, 2- and 3-dechloroethyifosfamide using gas chromatography with nitrogen-phosphorus or mass spectrometry detection

A comparison was made between methods for determining ifosfamide (IF), 2- (2DCE) and 3-dechloroethylifosfamide (3DCE) using gas chromatography with nitrogen-phosphorus detection (GC-NPD) versus positive ion electron-impact ion-trap mass spectrometry (GC-MS²). Sample pretreatment involved liquid-liquid extraction with ethyl acetate after adding trofosfamide as internal standard and alkalinization. The GC-NPD was linear, specific, and sensitive for all analytes in the range of 0.0500-100 μg/mL with lower limits of quantification (LLQ) of 0.0500 μg/mL using a 50-μL plasma sample. The GC-MS² was linear, specific, and sensitive for IF, 2DCE, and 3DCE in the ranges of 0.250-100, 0.500-25.0, and 0.500-25.0 μg/mL, respectively, with LLQs of 0.250, 0.500, and 0.500 μg/mL. The ranges of accuracy, within-day precision, and between-day precision for analysis of all compounds with GC-NPD did not exceed 93.3% to 105.4%, 8.0% and 9.8%, respectively. The ranges of accuracy, within-day precision, and between-day precision for analysis of all compounds with GC-MS² did not exceed 86.5% to 99.0%, 9.0% and 12.7%, respectively. In conclusion, GC-NPD proved to be superior to GC-MS² in sensitivity, detection range, accuracy, and precisions. Therefore GC-NPD is the method of choice for fast un-derivatized determination of IF, 2DCE, and 3DCE in human plasma, and it can readily be used for clinical pharmacokinetic studies and routine monitoring of IF-treated patients in a hospital setting.