A Method for the Quantification of Intracellular Zidovudine Nucleotides

Abstract
An assay to quantify the phosphorylation products of zidovudine (AZT) in peripheral blood mononuclear cells (PBMC) was developed. Extracts of PBMC were separated by high-performance liquid chromatography. Eluted AZT mono- (MP), di- (DP), and triphosphate (TP) were collected in separate portions. Treatment with alkaline phosphatase yielded equimolar amounts ofAZT, which after solid-phase enrichment were assayed by radioimmunoassay. Detection limit was 0.1 pmol/106 PBMC for each nucleotide. Recoveries of 102%–118% were observed. AZT nucleotides were measured in samples from three patients receiving 250 mg ofAZT every 12 h. Intracellular concentrations of AZT-MP after 1–2 h ranged from 0.9 to 1.4 pmol/106 PBMC and then declined to 0.3–1.1 pmol/106 PBMC after 4 h. AZT-DP and AZT-TP reached concentrations of 0.3–0.5 pmol/106 PBMC after 1–2 h and could not be detected after 4 h in any of the three patients. Duplicate determinations deviated by <20%.

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