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.
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Authors | L Hegedus, H Ford Jr, N R Hartman, J A Kelley |
Journal | Journal 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 |
PMID | 9187397
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- Blood Proteins
- Cytidine
- cyclopentenyl cytosine
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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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