Chemical stability of ecomustine, a new antitumor agent in aqueous and biological media as assessed by high-performance liquid chromatography.
Ecomustine, or CY233 (NSC-609224), is a new water-soluble nitrosoureido sugar derived from acosamine. A high-performance liquid chromatographic assay (HPLC) developed to quantify the unchanged drug in aqueous solutions and biological specimens enabled us to study the chemical stability as a function of pH, light, and temperature. In buffered aqueous solutions, the kinetics of degradation of CY233 is a first-order process. The log k-pH profile demonstrated hydroxide ion-catalyzed solvolysis. The drug is most stable at pH 4, more stable than some other nitrosoureas in 5% glucose (t1/2, 62-67 h) and in 0.9% isotonic saline (t1/2, 25-37 h) solutions. Based on these findings, blood samples should be collected in cold tubes (4 degrees C) containing citrate buffer (pH 4) and all manipulations should be protected from heat and light.
el Abed
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I
Laboratoire de Pharmacologie Clinique (URA 158 CNRS, U140 INSERM), Institut Gustave-Roussy, Villejuif, France.
Roger
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P
Gosse
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C
Atassi
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G
Gouyette
A
A
D000970:Antineoplastic Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009607:Nitrosourea Compounds / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D013696:Temperature
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; C058411:ecomustine