DETERMINATION OF THE ENANTIOMERS OF IFOSFAMIDE AND ITS 2-N-DECHLOROETHYL-ATED AND 3-N-DECHLOROETHYLATED METABOLITES IN PLASMA AND URINE USING ENANTIOSELECTIVE GAS-CHROMATOGRAPHY WITH MASS-SPECTROMETRIC DETECTION
Cp. Granville et al., DETERMINATION OF THE ENANTIOMERS OF IFOSFAMIDE AND ITS 2-N-DECHLOROETHYL-ATED AND 3-N-DECHLOROETHYLATED METABOLITES IN PLASMA AND URINE USING ENANTIOSELECTIVE GAS-CHROMATOGRAPHY WITH MASS-SPECTROMETRIC DETECTION, Journal of chromatography. Biomedical applications, 622(1), 1993, pp. 21-31
A rapid, sensitive, enantioselective gas chromatographic method has be
en developed for the quantitation of the enantiomers of ifosfamide (IF
F) 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 dech
loroethylated metabolites were extracted into chloroform, enantioselec
tively resolved by gas chromatography on a chiral stationary phase bas
ed upon heptakis(2,6-di-O -methyl-3-O-pentyl)-beta-cyclodextrin and qu
antitated 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-DC
E-IFF were 500 ng/ml. The method can detect concentrations as low as 2
50 ng/ml of each enantiomer of 2- and 3-DCE-IFF in plasma and urine. T
he intra- and inter-day coefficients of variation for this method were
with one exception less than 8%. The assay was validated for enantios
elective pharmacokinetic studies in humans and rats and is the first r
eported enantioselective assay for the measurement of the enantiomers
of 2- and 3-DCE-IFF in plasma.