Analysis of ifosfamide, 4-hydroxyifosfamide, N2-dechloroethylifosfamide, N3-dechloroethylifosfamide and iphosphoramide mustard in plasma by gas chromatography-mass spectrometry.
A sensitive and specific method for the simultaneous quantitation of ifosfamide (IF), 4-hydroxylifosfamide (4-OHIF), N2-dechloroethylifosfamide (N2D), N3-dechloroethylifosfamide (N3D) and iphosphoramide mustard (IPM) has been developed using gas chromatography-mass spectrometry (GC-MS) with an ion-trap mass spectrometer. Deuterium labeled analogues for each of these analytes were synthesized as the internal standards. The labile 4-OHIF in plasma was first converted to the more stable cyanohydrin adducts before dichloromethane extraction. IPM was extracted by C18 reversed-phase resin. All analytes were converted to their silyl derivatives before GC-MS analysis. The sensitivity limits ranged from 0.1 to 0.5 microgram/ml when 100 microliters of plasma was used. This method was validated with within-run coefficients of variation less than 5% (n = 8) and between-run coefficients of variation less than 12% (n = 6). The method was applied to the determination of plasma levels of IF and metabolites in the rat.
Wang
J J
JJ
School of Pharmacy, University of Southern California, Los Angeles 90033, USA.
Chan
K K
KK
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000097:blood*; D003903:Deuterium; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods* / Q000706:statistics & numerical data; D007069:Ifosfamide / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D007700:Kinetics; D008297:Male; D010752:Phosphoramide Mustards / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018906:Antineoplastic Agents, Alkylating; D010752:Phosphoramide Mustards; C027061:isophosphamide mustard; D003903:Deuterium; C038007:dechloroethylifosfamide; D007069:Ifosfamide