基于QBD的枸橼酸西地那非清洁残留物的分析方法开发与验证

Based On QBD to Develop and Validate the Analysis Method for the Sildenafil Citrate Cleaning Residue

目的:对枸橼酸西地那非生产设备清洁残留,采用QBD进行分析方法开发与验证。方法:经过方法设计(第1阶段)、方法确认(第2阶段)和持续方法确证(第3阶段),色谱柱为C18(3.9 mm×150 mm,5.0μm);流动相为0.05 mol/L三乙胺磷酸盐溶液(取三乙胺7 m L,加水1000m L,用磷酸调p H至3.0)-乙腈-甲醇(58∶17∶25);流速为1.0 m L/min;检测波长为290 nm;柱温为30℃;进样量为20μL。结果:检测限为0.028μg/m L,相当于下一批0.02 ppm的限度;在0.028~28.0μg/m L(R2=0.9999,n=6)范围内与峰面积线性关系良好;方法平均回收率为99.95%,RSD=0.09%(n=9);取样平均回收率为98.63%,RSD=0.33%(n=9)。结论:实践证明,基于QBD是一种科学知识与风险评估有机结合的现代分析方法开发与验证的方法。

Objective Based on QBD to develop and validate the analytical method for the clean residue of sildenafil citrate during rnanufacturing. Method Through method design （phase I）, method validation （phase 2） and continuous method validation （phase 3）, chromatographic column is C18 column（3.9 mm×150 mm, 5.0 μm）; for mobile phase, mix 17 volumes of acetonitrile R, 25 volumes of methanol R and 58 volumes of a 0.7 per cent V/V solution of triethylamine R previously adjusted to pH 3.0 ± 0.1 with phosphoric acid R. The detection wavelength is 290 nm and the flow rate is 1.0 ML/min. The column temperature is 30 ℃. The injection volume is 20 μL. Results The LOD is 0.028 μg/mL, 0.02 ppm; The calibration curves is linear in the range of 0.028-28.0 μg/mL（R2=0.9999, n=6）. The average recovery rates are 99.95 %, RSD=0.09 % （n=9） for analytical method and 98.63 %, RSD=0.33 % （n=9） for sampling method. Conclusion Practice has proved that QBD is a modern method combining scientific knowledge with risk assessment to develop and validate the analytical method.