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 microg/mL with lower limits of quantification (LLQ) of 0.0500 microg/mL using a 50-microgL 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 microg/mL, respectively, with LLQs of 0.250, 0.500, and 0.500 microg/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.
Kerbusch
T
T
Department of Pharmacy, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam.
Jeuken
M J
MJ
Derraz
J
J
van Putten
J W
JW
Huitema
A D
AD
Beijnen
J H
JH
D018906:Antineoplastic Agents, Alkylating / Q000032:analysis* / Q000493:pharmacokinetics; D002849:Chromatography, Gas / Q000592:standards; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000032:analysis* / Q000493:pharmacokinetics; D016903:Drug Monitoring / Q000592:standards*; D008401:Gas Chromatography-Mass Spectrometry / Q000592:standards; D006801:Humans; D007069:Ifosfamide / Q000031:analogs & derivatives* / Q000032:analysis* / Q000493:pharmacokinetics; D011786:Quality Control; D012680:Sensitivity and Specificity
D018906:Antineoplastic Agents, Alkylating; C064445:dechloroethylcyclophosphamide; D003520:Cyclophosphamide; C038007:dechloroethylifosfamide; D007069:Ifosfamide