[Studies on the stability of aclacinomycin hydrochloride. I. Stability of solution of aclacinomycin hydrochloride (author's transl)].
Aclacinomycin is an antitumor anthracycline antibiotic isolated from the culture broth of Streptomyces galilaeus MA144-M1. In this study, the effects of heat, light and pH on the aqueous solution of aclacinomycin hydrochloride (ACM-HCl) were investigated. The following results were found: (1) The kinetic studies revealed that the thermal inactivation of ACM-HCl solution (pH 4.5) was based on the apparent first-order reaction and that Arrhenius equation was confirmed to be established between the rate constants and temperatures. When ACM-HCl solution was stored at 20, 10 and 5 degrees C, the estimated term of ACM-HCl solution at the time when the initial activity (100%) reduced to 90% residual concentration was 1.5, 6 and 12 months, respectively. (2) It was clarified by pH-log k profile that ACM-HCl  solution was most stable near at pH 4.5. (3) The higher the buffer concentration was used, the faster the degradation rate, but there was no difference between the residual activity ratios at the various concentrations of ACM-HCl solution. (4) The inactivation of ACM-HCl solution under sunlight occurred in a type of zero-order reaction so that the faster inactivation rates were obtained at the more diluted concentration of ACM-HCl. (5) The major degradation products of ACM-HCl solution were 1-deoxypyrromycin (DP), MA144 S1 (S1) and bisanhydroaklavinone (F1). DP and S1 were mainly found at pH below 4.0 and F1 at pH above 5.0. The degradation under sunlight gave L1 (N-monodemethyl ACM) accompanied by the degradation of aglycone moiety in part.
D015250:Aclarubicin / Q000031:analogs & derivatives*; D000903:Antibiotics, Antineoplastic; D004355:Drug Stability; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D007477:Ions; D008027:Light; D009279:Naphthacenes; D012996:Solutions; D014867:Water
D000903:Antibiotics, Antineoplastic; D007477:Ions; D009279:Naphthacenes; D012996:Solutions; C011157:aclacinomycins; D014867:Water; D015250:Aclarubicin