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 microm, 250 mm x 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 lnk(i)=f(1/T) was described by the equations lnk(DOX)=40.0+/-15.6-(19804+/-5682) (1/T) and lnk(DAU)=35.9+/-11.3-(16581+/-3972) (1/T) at 76.4% RH. The dependence lnk(i)=f(RH%) was described by the equations lnk(DOX)=(8.80+/-3.60) x10(-2) (RH%)-(21.50+/-2.57) and lnk(DAU)=(6.63+/-1.22)x10(-2) (RH%)-(13.35+/-1.68). The thermodynamic parameters (E(a,) DeltaH(not = a), DeltaS(not = 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.
Cielecka-Piontek
J
J
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland. jpiontek@ump.edu.pl
Jelińska
A
A
Zajac
M
M
Sobczak
M
M
Bartold
A
A
Oszczapowicz
I
I
D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003630:Daunorubicin / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry*; D004355:Drug Stability; D006813:Humidity; D007700:Kinetics; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013696:Temperature; D013816:Thermodynamics
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D003630:Daunorubicin