Evaluation of Stability of Temozolomide in Solutions after Opening the Capsule

• Published in: YAKUGAKU ZASSHI Vol. 129; no. 3; pp. 353 - 357
• Main Authors: KODAWARA, Takaaki, MIZUNO, Tomoyuki, TAUE, Hiromi, HASHIDA, Tohru, YANO, Ikuko, KATSURA, Toshiya, INUI, Ken-ichi
• Format: Journal Article
• Language: Japanese
• Published: Japan The Pharmaceutical Society of Japan 01.03.2009
• Subjects: Antineoplastic Agents, Alkylating; antitumor agent; Buffers; Capsules; Dacarbazine - analogs & derivatives; Drug Stability; glioma; Hydrogen-Ion Concentration; Solutions; stability; Temozolomide; Time Factors; Water
• ISSN: 0031-6903; 1347-5231
• 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 μg/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.