Determination of Ara-C in plasma and Ara-CTP in leukemic cells after intravenous infusion of high-dose Ara-C in patients with acute leukemia and analysis of influence factors / 白血病·淋巴瘤

ABSTRACT

Objective To determine the plasma and intracellular concentration of Ara-C by the RPHPLC method and analyse the influence factors and the relationship between the concentration and drug dose.Methods Mononuclear cells and serum of 75 patients with acute leukemia were extracted after the first intravenous infusion of different administration dosage of Ara-C (0.5, 1.0, 2.0 g/m2), and analysed with different chromatographic conditions by RP-HPLC. Results The linear range of Ara-CTP was 0.28-18.96 μg/ml (r =0.998), and the detection limit was 0.28 μg/ml. The detection limit of Ara-C and Ara-U in plasma was 0.0157 μg/ml and 1.034 μg/mnl respectively. In 27 samples preserved for more than 1.5 years, 11 (40.7 %)cases of the plasma concentration of Ara-C were below the detection limit. In 36 samples of mononuclear cell count below 1.5×106/ml, 15 cases (41.7 %) of intracellular concentration of Ara-CTP were below the detection limit. The plasma concentration of Ara-U and intracellular concentration of Ara-CTP were increased with administration dosage of Ara-C increased, and the plasma concentration of Ara-C was not increased. The intracellular concentration of Ara-CTP in old patients over 40 years was tend to in crease with age.Conclusion The RP-HPLC method is simple, rapid, stable, reproducible and applicable for the monitoring of the plasma concentration of Ara-C and intracellular concentration of Ara-CTP. In 0.5-2.0 g/m2 dose range of Ara-C, the plasma concentration of Ara-U and intracellular concentration of Ara-CTP was increased with administration dosage of Ara-C increased.