Determination of the enantiomers of ifosfamide and its 2- and 3-N-dechloroethylated metabolites in plasma and urine using enantioselective gas chromatography with mass spectrometric detection.
A rapid, sensitive, enantioselective gas chromatographic method has been developed for the quantitation of the enantiomers of ifosfamide (IFF) and its 2- and 3-dechloroethylated metabolites (2-DCE-IFF and 3-DCE-IFF) in human and animal plasma and human urine. IFF and the two dechloroethylated metabolites were extracted into chloroform, enantioselectively resolved by gas chromatography on a chiral stationary phase based upon heptakis(2,6-di-O-methyl- 3-O-pentyl)-beta-cyclodextrin and quantitated using mass-selective detection with selected-ion monitoring. The limits of quantitation for the enantiomers of IFF, 2-DCE-IFF and 3-DCE-IFF in plasma were 250 and 500 ng/ml respectively. In urine, the limits of quantitation for the enantiomers of IFF, 2-DCE-IFF and 3-DCE-IFF were 500 ng/ml. The method can detect concentrations as low as 250 ng/ml of each enantiomer of 2- and 3-DCE-IFF in plasma and urine. The intra- and inter-day coefficients of variation for this method were with one exception less than 8%. The assay was validated for enantioselective pharmacokinetic studies in humans and rats and is the first reported enantioselective assay for the measurement of the enantiomers of 2- and 3-DCE-IFF in plasma.
Granville
C P
CP
Department of Oncology, McGill University, Montreal, Que., Canada.
Gehrcke
B
B
König
W A
WA
Wainer
I W
IW
D000818:Animals; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007069:Ifosfamide / Q000031:analogs & derivatives / Q000032:analysis* / Q000097:blood / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013237:Stereoisomerism; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000652:urine
C064445:dechloroethylcyclophosphamide; D003520:Cyclophosphamide; C038007:dechloroethylifosfamide; D007069:Ifosfamide