Enantiomeric separation of R- and S-ifosfamide and their determination in serum from clinical subjects.
A method to measure racemic, R- and S-ifosfamide concentrations from the serum of patients receiving ifosfamide chemotherapy has been developed. The racemic ifosfamide concentrations are quantified on a separate system and then the ratio of the enantiomers is determined using an achiral-chiral coupled system. Racemic ifosfamide is separated on the achiral system using a C1 spherisorb stationary phase and the eluent containing analyte is selectively transferred to the chiral system for separation of the two enantiomers by an alpha 1 glycoprotein column. On both systems the mobile phase is 1% acetonitrite in 0.015 M phosphate buffer (pH 4) at a flow-rate of 1 ml/min. The retention times of S- and R-ifosfamide were 11.6 and 13.0 mins, respectively, with a resolution factor of 1.53. Serum concentrations at least three to four half-lives post-infusion were detected by this method. In ten patients, following a mean +/- S.D. 1-h infusion of 3.9 +/- 0.32 g racemic ifosfamide, the mean +/- S.D. clearances of R- and S-ifosfamide were 0.061 +/- 0.013 and 0.072 +/- 0.014 1 h-1 kg-1.
Corlett
S A
SA
Pharmacy Practice, Postgraduate Studies in Pharmaceutical Technology, School of Pharmacy, University of Bradford, UK.
Chrystyn
H
H
D000368:Aged; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D006207:Half-Life; D006801:Humans; D007069:Ifosfamide / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D008875:Middle Aged; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
D007069:Ifosfamide