A comparison of the stability of doxorubicin and daunorubicin in solid state

The degradation of doxorubicin and daunorubcin in the solid state was studied using an HPLC method with UV detection (LiChrospher RP-18, 5 μm, 250 mm × 4 mm; mobile phase: acetonitrile-solution A 1:1, v/v (solution A: 2.88 g of laurisulfate sodium and 1.6 ml of phosphoric acid(V) in 1000 ml); flow rate – 1.4 ml min−1; UV detection – 254 nm). The degradation of doxorubicin was a first-order reaction depending on the substrate concentration and daunorubicin degraded according to the kinetic model of autocatalysis. The dependence ln ki = f(1/T) was described by the equations ln kDOX = 40.0 ± 15.6 – (19804 ± 5682) (1/T) and ln kDAU = 35.9 ± 11.3 – (16581 ± 3972) (1/T) at 76.4% RH. The dependence ln ki = f(RH%) was described by the equations ln kDOX = (8.80 ± 3.60) × 10−2 (RH%) – (21.50 ± 2.57) and ln kDAU = (6.63 ± 1.22) × 10−2 (RH%) – (13.35 ± 1.68). The thermodynamic parameters (Ea, ΔH≠a, ΔS≠a) of the degradation of doxorubicin and daunorubicin were calculated. Although the degradation of doxorubicin was slower at increased temperature (353–373 K) and relative air humidity (50.9–90.0%), the differences between the influence of temperature and relative air humidity on the stability doxorubicin and of daunorubicin were not significant.