Photostability profiles of the experimental antimetastatic ruthenium complex NAMI-A

被引:18
作者
Bouma, M
Nuijen, B
Jansen, MT
Sava, G
Bult, A
Beijnen, JH
机构
[1] Netherlands Canc Inst, Slotervaart Hosp, Dept Pharm & Pharmacol, NL-1066 EC Amsterdam, Netherlands
[2] Fdn Callerio Onlus, I-34127 Trieste, Italy
[3] SIGEA SRL, I-34012 Trieste, Italy
[4] Univ Utrecht, Fac Pharmaceut Sci, NL-3584 CA Utrecht, Netherlands
关键词
NAMI-A; photostability; photodegradation;
D O I
10.1016/S0731-7085(02)00458-2
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
NAMI-A is a novel ruthenium complex with selective activity against metastases currently in Phase I clinical trials in The Netherlands. The photostability of this new agent in solid state and in solution has been investigated utilizing a stability-indicating reversed-phase high performance liquid chromatographic (HPLC) assay and ultraviolet/visible (UV/ VIS) light spectrophotometry. In solid state, NAMI-A proved to be photostable. In solution, however, the compound degraded rapidly, in a pH-independent manner in the pH range of 2-5. At alkaline pH, the degradation rate was higher than at acidic pH. The type of buffer species had little influence. NAMI-A concentration was inversely related to the photostability. Addition of photostabilizers (5% DMSO, 2% benzyl alcohol, 0.001% curcumin) marginally increased the half-life. NAMI-A's photostability in solution was influenced to the greatest extent by addition of an alcohol, with the least polar solvent system (50% propylene glycol) providing the most stable medium. Based on the presented results, it is recommended to store NAMI-A solutions in the dark. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:1287 / 1296
页数:10
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