Abstract
Rapid and quantitative dephosphorylation of the new anticancer nucleotide analogue fludarabine phosphate to its nucleoside 9-β-D-arabinofuranosyl-2-fIuoroadenine (F-ara-A) renders this metabolite the target for pharmacologic investigations. At clinically effective doses of fludarabine phosphate (18-30 mg/m2 per day) comprehensive pharmacokinetic analysis of F-ara-A has been limited by the sensitivity of UV based HPLC assays. To address this problem we developed a sensitive test based on the condensation of F-ara-A with chloroacetaldehyde to form the fluorescent derivative, arabinosyl-1, N6-etheno-isoguanine. Combined with a solid-phase extraction step prior to derivatization and separation of the reaction products by reverse-phase HPLC, this assay had a quantitation limit of 2 pmol F-ara-A per ml plasma. Slightly modified, the system was also applicable to urine specimens, with a quantitation limit of 1 nmol F-ara-A per ml urine.
Original language | English (US) |
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Pages (from-to) | 95-106 |
Number of pages | 12 |
Journal | Clinica Chimica Acta |
Volume | 200 |
Issue number | 2-3 |
DOIs | |
State | Published - Aug 30 1991 |
Keywords
- Biological fluids
- Fludarabine
- Fluorescence assay
ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry
- Biochemistry, medical