Analytical and preparative high-performance liquid chromatographic separation of the enantiomers of ifosfamide, cyclophosphamide and trofosfamide and their determination in plasma

J Chromatogr. 1989 May 5;490(1):133-43. doi: 10.1016/s0378-4347(00)82768-1.

Abstract

A high-performance liquid chromatography chiral stationary phase (HPLC-CSP) based upon cellulose-tris(3,5-dimethylphenylcarbamate), the OD-CSP, was used to stereochemically resolve three racemic anticancer drugs: ifosfamide (IFF), cyclophosphamide (CTX) and trofosfamide (TFF). The observed enantioselectivities (alpha) were 1.45 (IFF), 1.21 (CTX) and 1.10 (TFF). The OD-CSP was also used on a preparative scale to isolate the enantiomers of IFF with an optical purity greater than 97%. In addition, an analytical assay was developed for the determination of the enantiomeric composition of IFF and CTX in plasma using achiral-chiral coupled column chromatography. A racemic form of another CSP, the D,L-naphthylalanine-CSP, was used as the achiral pre-column. The sample clean-up prior to HPLC analysis was realized by liquid-liquid extraction with chloroform. The correlation coefficient was 0.987 for both standard curves (20-130 micrograms/ml) and the controls were within 10% of the real value. The analysis time for each serum sample was less than 30 min.

MeSH terms

  • Antineoplastic Agents / blood
  • Chemical Phenomena
  • Chemistry
  • Chromatography, High Pressure Liquid
  • Cyclophosphamide / analogs & derivatives*
  • Cyclophosphamide / blood*
  • Humans
  • Ifosfamide / blood*
  • Stereoisomerism

Substances

  • Antineoplastic Agents
  • Cyclophosphamide
  • trofosfamide
  • Ifosfamide