QUANTITATION OF 1-BETA-D-ARABINOFURANOSYLCYTOSINE 5'-TRIPHOSPHATE IN THE LEUKEMIC-CELLS FROM BONE-MARROW AND PERIPHERAL-BLOOD OF PATIENTS RECEIVING 1-BETA-D-ARABINOFURANOSYLCYTOSINE THERAPY

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (3) , 588-591
Abstract
A method for the detection and quantitation of 1-.beta.-D-arabinofuranosylcytosine 5''-triphosphate (ara-CTP), the active metabolite of 1-.beta.-D-arabinofuranosylcytosine (ara-C), in the bone marrow cells and leukemic cells of the peripheral blood from patients receiving ara-C therapy is described. ara-CTP is separated from normal cellular nucleotides by high-pressure liquid chromatography and is quantitated by its absorbance of UV light at 280 nm with a lower limit of sensitivity of 25 pmol/2 .times. 107 cell equivalents. During separate courses of continuous infusion of different therapeutic doses of ara-C, ara-CTP accumulated in the leukemic bone mrrow cells of a patient with acute myelogenous leukemia in proportion to the dose of ara-C. Continuous infusion of ara-C (90 mg/sq m per day) resulted in plateau levels of ara-CTP in peripheral blast cells after 24 h (115 pmol/1 .times. 107 cell equivalents). A priming dose of ara-C (125 to 250 mg/sq m) followed by a 1-h infusion of an equal dose of ara-C to patients with acute myelogenous leukemia facilitated the determination of ara-CTP retention in bone marrow and peripheral blood leukemic cells in vivo. This procedure should be useful for extended studies of the biochemical pharmacology of ara-CTP in vivo.