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Reversed-phase high-performance liquid chromatographic determination of the new antitumor agent cyclopentenyl cytosine in biological fluids.

Abstract
Cyclopentenyl cytosine (CPE-C) is a synthetic carbocyclic nucleoside that possesses diverse antitumor and antiviral activity. CPE-C has been studied extensively at the preclinical level and has been evaluated in a Phase I clinical trial involving patients with solid tumors. A narrow-bore, reversed-phase HPLC method that has been developed for the sensitive measurement of CPE-C in plasma and urine in order to carry out these studies is described. Covalent solid-phase extraction based on an immobilized phenylboronic acid ligand is employed to isolate both CPE-C and endogenous ribonucleosides from the biological matrix selectively and efficiently. This is followed by isocratic elution of the extract with pH 5.0, 0.1 M ammonium formate buffer at 0.150 ml/min on a tandem, switchable, C18 narrow-bore (2.1 mm I.D.) column system in which the precolumn is automatically backflushed to eliminate late-eluting components. UV detection at 278 nm provides a limit of quantitation of 0.1 microM for CPE-C in rat and human plasma with a precision better than 4% for the range 1-20 microM in rat plasma. Application of this assay to the determination of the bolus dose plasma kinetics and disposition of 2 mg/kg CPE-C in rats is illustrated. This method is amenable to partial automation and is well-suited for the analysis of clinical samples.
AuthorsL Hegedus, H Ford Jr, N R Hartman, J A Kelley
JournalJournal of chromatography. B, Biomedical sciences and applications (J Chromatogr B Biomed Sci Appl) Vol. 692 Issue 1 Pg. 169-79 (Apr 25 1997) ISSN: 1387-2273 [Print] Netherlands
PMID9187397 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents
  • Blood Proteins
  • Cytidine
  • cyclopentenyl cytosine
Topics
  • Animals
  • Antineoplastic Agents (blood, pharmacokinetics, urine)
  • Blood Proteins (metabolism)
  • Chromatography, High Pressure Liquid
  • Cytidine (analogs & derivatives, blood, pharmacokinetics, urine)
  • Dogs
  • Drug Stability
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Male
  • Protein Binding
  • Rats
  • Rats, Sprague-Dawley
  • Spectrophotometry, Ultraviolet

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