注射用雷替曲塞的稳定性试验研究

Study on Stability of Raltitrexed for Injection

目的:考察注射用雷替曲塞的稳定性,为临床贮存、使用药品提供科学依据。方法:按2010年版《中国药典》药物制剂稳定性试验指导原则进行影响因素试验[60、40℃高温试验,25℃、相对湿度92.5%高湿度试验和(4 500±500)lx强光照试验]、加速试验(40℃、相对湿度75%和30℃、相对湿度65%)和长期试验(25℃、相对湿度60%,12个月),考察注射用雷替曲塞在不同试验条件下的外观性状、pH、有关物质和主成分含量变化,采用高效液相色谱法测定有关物质和主成分含量。结果:影响因素试验显示,样品在60℃及强光照条件下含量降低,有关物质明显增加;而加速试验和长期试验考察结果显示各项质量指标未见明显变化。结论:注射用雷替曲塞在高温及强光照条件下不稳定,建议在20℃避光、密闭条件下贮存。

OBJECTIVE： To investigate the stability of Raltitrexed for injection, and to provide scientific basis for storage and utilization of drugs. METHODS： The appearance, pH, related substances and contents of Raltitrexed for injection were investigated by influential factor test [high temperature test （60 ℃ and 40 ℃ ）, high humidity test （25 ℃, relative humidity 92.5% ） and （4 500 ± 500） lx strong light test], accelerated test [40 ℃ （relative humidity 75% ）, 30 ℃ （relative humidity 65% ）] and long-term test [25 ℃ （relative humidity 60% ） for 12 months], according to the guidance for stability test of preparation stated in Chinese Pharmacopeia （2010 edition）. HPLC was used to determine its contents and its related substances. RESULTS： Results of influen- tial factor tests showed that the contents of raltitrexed decreased and related substances increased markedly under 60 ℃ and strong light conditions. Results of accelerated test and long-term test showed that no significant change was observed in quality specifica- tions. CONCLUSIONS： Under the condition of strong light and high temperature, Raltitrexed for injection is not stable. It should be kept in light-resistant, sealed container at 20 ℃.