氟尿嘧啶原料药的质量控制及稳定性研究

Study on quality control and stability of fluorouracil bulk drug

目的建立抗肿瘤药氟尿嘧啶原料药的质量控制方法，并考察其稳定性。方法采用高效液相色谱法测定氟尿嘧啶原料药含量和有关物质，并对其进行稳定性考察。结果建立了氟尿嘧啶原料药的质量控制方法，包括性状、鉴别、干燥失重（≤0．3％）、炽灼残渣（≤0．1％）、重金属（≤0．002％）、有关物质（≤0．5％）和含量测定（98．0％～102．0％），样品检测结果在规定的限度内。对氟尿嘧啶样品进行了影响因素试验考察，在高温、高湿条件下无明显降解。在光照5、10d条件下含量均无明显变化，并分别在加速试验[（40±2）℃，相对湿度75％±5％]条件下进行了6个月和长期试验[（30±2）℃，相对湿度60％±5％]条件下进行了9个月的稳定性试验，稳定性考察期内各项指标未见明显变化。结论所建立的氟尿嘧啶原料药质量控制方法重复性好、专属性强，结果准确、可靠，耐用性检测结果在规定的限度内，氟尿嘧啶原料药稳定性良好。

Objective To establish the quality control method of antitumor drug fluorouracil bulk drug and to investigate its stability. Methods The content and related substances in fluorouracil bulk drug were determined by high performance liquid chromatography （HPLC） and its stability was investigated. Results The quality control method of fuorouracil bulk drug was estab- lished,including character,identification,drying loss （ ≤0.3% ） ,residue on ignition （ ≤0.1% ） ,heavy metals （ ≤0.002% ） ,related substances （≤0.5%） and content determination（98.0%-102.0%）. The sample test results were all within the limits specified. Mean- while,the fuorouracil sample was performed the influencing factor test,the results showed that there was no obvious fluorouracil degradation under the condition of high temperature and high humidity,there were no obvious changes under the condition of 5,10 d illumination, the 6-month and 9-month stability tests were performed in the condition of the accelerated testing[（40±2）℃, relative humidity （RH）75%±5%] and the long-term testing[ （30±2）℃, RH 50%±5%] respectively, the various indicators had no obvious changes during the stability investigation period. Conclusion The established quality control method of fluorouracil bulk drug has good repeatability, strong specificity, and accurate and reliable results, the detection results of the durability test are within the lim- its specified, fluorouracil bulk drug has good stability.