Highly sensitive high-performance liquid chromatographic assay for 1-beta-D-arabinofuranosylcytosine-5'-stearyl phosphate (cytarabine-ocfosfate).
An ion-pair HPLC method for the determination of 1-beta-D-arabinofuranosylcytosine-5'-stearyl phosphate (cytarabine-ocfosfate I) was developed, using a phenyl-bonded column under reversed-phase conditions with a mobile phase of acetonitrile-buffered water (pH 6.8) (50:50) for isocratic elution. A reproducible sample clean-up was achieved by solid-phase extraction. In order to reach the low limit of detection of 2 ng/ml, an enrichment switching system was used. The present validation leads to a limit of quantification of 5 ng/ml with a coefficient of variation (C.V.) of 10%. The total time of measurement was shortened by a back-flush procedure to restore the conditions after each run. UV detection at 275 nm was applied. The recoveries for plasma samples ranged from 56.4 to 64.1%, regardless of drug concentrations. The intra-assay C.V. was about 4% (40 measurements at four different concentrations). The inter-assay recovery (ten measurements over ten days) at a plasma concentration of 50 ng/ml was 57% with a C.V. of 8.25%. Based on this HPLC method, the pharmacokinetics of I were measured during a clinical phase I/II study.
Ramsauer
B
B
Department of Hematology and Oncology, University of Göttingen, Germany.
Braess
J
J
Unterhalt
M
M
Kaufmann
C C
CC
Hiddemann
W
W
Schleyer
E
E
D000970:Antineoplastic Agents / Q000032:analysis* / Q000097:blood / Q000652:urine; D001088:Arabinonucleotides / Q000032:analysis* / Q000097:blood / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003568:Cytidine Monophosphate / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000652:urine; D004355:Drug Stability; D006801:Humans; D015203:Reproducibility of Results
D000970:Antineoplastic Agents; D001088:Arabinonucleotides; C061162:1-arabinofuranosylcytosine-5'-stearylphosphate; D003568:Cytidine Monophosphate