氟尿嘧啶原料及注射液中有关物质的定性及定量分析

目的:建立氟尿嘧啶原料及注射液中的5种有关物质的定性及定量分析方法。方法: 采用高效液相色谱法,色谱柱:Kromacil C₁₈柱(250 mm×5 mm,5 μm);流动相:甲醇-水(磷酸调 pH为3.5)(5:95);流速:1.0 mL·min^-1;检测波长:265 nm;柱温;35℃。分别采用标准曲线法、不加校正因子的主成分自身对照法以及加校正因子的主成分自身对照法对有关物质进行定量分析。结果: 分别测得了5种有关物质对照品的标准曲线、线性范围、相对保留时间及校正因子,各对照品的平均回收率均在95%以上,精密度和重现性的平均RSD均在1.5%以下;通过比较认为,加校正因子的主成分自身对照法计算有关物质的含量更准确、简便。结论: 本方法可用于氟尿嘧啶原料及注射液中有关物质的定性及定量分析,杂质D的计算采用加校正因子的主成分自身对照法(校正因子1.5)可以更准确的反映其有关物质的含量。

Objective: To establish a qualitative and quantitative analysis method for the determination of the 5 related substances in fluorouracil raw materials and its injection. Methods: The high-performance liquid chromatography (HPLC) was used for the analysis,a Kromacil C₁₈ column (250 mm×5 mm,5 μm) was used as the analytical column,methanol-water (phosphoric acid adjusted to pH 3.5) (5:95) were used as the mobile phase at a flow rate of 1.0 mL·min^-1,the detection wavelength was 265 nm,and the column temperature was 35℃.The standard curve method,and the main component self control method with and without correction factor were used for the quantitative analysis of the related substances respectively. Results: The regression equation,linear range,relative retention time,and correction factor of five related substances were measured respectively.The average recovery of each reference substance was more than 95%,and the average RSD values for precision and reproducibility were both less than 1.5%.By comparison,the main component self control method with correction factor was more accurate and simple to calculate the content of related substances. Conclusion: The method can be used for the qualitative and quantitative analysis of the related substances in fluorouracil injection and raw materials,and the main component self control method with correction factor can reflect the content of impurities D (correction factor 1.5) more accurately.