Kodawara Takaaki, Mizuno Tomoyuki, Taue Hiromi, Hashida Tohru, Yano Ikuko, Katsura Toshiya, Inui Ken-Ichi
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto, Japan.
Yakugaku Zasshi. 2009 Mar;129(3):353-7. doi: 10.1248/yakushi.129.353.
We evaluated the stability of temozolomide, an alkylating agent, in solutions after opening the capsule. First, we established an analytical method for determination of temozolomide concentration by HPLC. The calibration curve for temozolomide was linear between 0.5-20 microg/ml (r=0.999). We then evaluated the stability of temozolomide in each buffer solution (pH 2-9) for 30 min. Temozolomide was decomposed pH-dependently between pH 7 and 9, and completely decomposed at pH 9. Temozolomide in several drinking water samples and beverages was decomposed according to their pH values. We also examined the time-dependent degradation of temozolomide in different pH solutions. Temozolomide started to decompose at 5 min in alkaline and neutral solutions, whereas 90% of temozolomide remained intact in acidic solution at 60 min. These results indicate that the stability of temozolomide after opening the capsule is affected by pH of solvents, and temozolomide is almost stable in acidic solutions.
我们评估了烷基化剂替莫唑胺在打开胶囊后的溶液中的稳定性。首先,我们建立了一种通过高效液相色谱法测定替莫唑胺浓度的分析方法。替莫唑胺的校准曲线在0.5 - 20微克/毫升之间呈线性(r = 0.999)。然后我们评估了替莫唑胺在每种缓冲溶液(pH 2 - 9)中30分钟的稳定性。替莫唑胺在pH 7至9之间随pH值依赖性分解,并在pH 9时完全分解。几种饮用水样品和饮料中的替莫唑胺根据其pH值分解。我们还研究了替莫唑胺在不同pH溶液中的时间依赖性降解。替莫唑胺在碱性和中性溶液中5分钟开始分解,而在酸性溶液中60分钟时90%的替莫唑胺保持完整。这些结果表明,打开胶囊后替莫唑胺的稳定性受溶剂pH值影响,且替莫唑胺在酸性溶液中几乎稳定。