Chemical stability of pentostatin (NSC-218321), a cytotoxic and immunosuppressant agent.

摘要: Pentostatin, an unusual nucleoside of natural origin, has been used for the treatment hairy cell leukemia, as immunosuppressant agent, and inhibitor adenosine deaminase. The studies physicochemical properties solution stability pentostatin (1) are important to development a parenteral formulation extensive preclinical clinical testing. Pentostatin displayed apparent pK a values at 25 ± 0.1°C ionic strength 0.15 M 2.03 0.03 5.57 0.14 (spectrophotometric) 5.50 0.02 (potentiometric) N1 amidine nitrogen in seven-membered ring, respectively, which most likely protonation sites. rates degradation were determined function pH, buffer concentration, temperature. In pH range 1.0–4.0, undergoes acid-catalyzed glycosidic cleavage leading formation base compound, 2, 2-deoxyribose. A carbonium ion mechanism C–N bond was rate-determining step consistent with data. 6.5–10.5, imine C5 position is hydrolyzed form corresponding formamide. hydrolysis this independent pH. At >11, decomposes nonchromophoric products probably through multiple-step base-catalyzed hydrolytic mechanisms. appears be quite stable after reconstitution lyophilized experimental dosage form. Care must taken if extensively diluted 5% dextrose water, compromised less than 5.