3--周立春--仿制药一致性评价药学研究的关键点.ppt

例：盐酸格拉司琼片（中国药典） 色谱条件与系统适用性试验 用氰基硅烷键合硅胶为填充剂；以含0. 25 % (ml/ml)三乙胺的0. 05mol/L醋酸钠溶液（用冰醋酸调节p H 值至6. 0)-甲醇（50 : 50)为流动相；检测波长为3 0 2 n m。理论板数按格拉司琼峰计算不低于2000。取本品适量，加溶剂（取磷酸0. 1 6 m l加水至80ml，加乙腈20ml，混匀，加己胺0. 1ml，用三乙胺调p H值至7. 5)溶解并稀释制成每l m l中约含0. 5 m g 的溶液，取适量，置试管中，密塞，在强光下照射4 小时，作为系统适用性溶液，取20μl注人液相色谱仪，记录色谱图，格拉司琼峰前应产生明显的光降解产物峰，格拉司琼峰与光降解产物峰的分离度应符合要求。 杂质限度：各杂质峰面积的和不得大于对照溶液主峰面积（1.0% ) 。 * 欧洲药典 Column：—size:l=0.25m,?=4.6mm; —stationaryphase:spherical base-deactivatedend-capped octadecylsilylsilicagelforchromatographyR(5μm); temperature:40°C. Mobilephase:dilute1.6mLof phosphoricacidR to 800mL with waterR,add 200mL of acetonitrileR andmix.Add1.0mLof hexylamineR and mix.AdjusttopH7.5±0.05 with freshly distilled triethylamineR (about4mL). Flowrate:1.5mL/min. s * Detection:spectrophotometer at 305nm. Systemsuitability:—resolution:minimum3.5 between the peaks due to impurityC and granisetron in the chromatogram obtained with referencesolution(b); ymmetryfactor:maximum2.0f or the peak due to granisetron. Limits:correctionfactor:for the calculation of content,multiply the peak area of impurityB by1.7; impurityB:not more than the area of the principal peak in the chromatogram obtained with reference solution(a)(0.5percent); impurityC:not more than 0.4 times the area of the principal peak in the chromatogram obtained with reference solution(a)(0.2percent); impurityA:not more than twice the area of the principal peak in the chromatogram obtained with reference solution(a)(1.0percent); impurityD:not more than 0.2 times the area of the principal peak in the chromatogram obtained with referencesolution(a)(0.1percent); anyotherimpurity:for each impurity, not more than 0.2 times the area of the principal peak in the chromatogram obtained with reference solution(a)(0.1percent); total:not more than twice the area of the principal peak in the chromatogram obtained with reference solution(a)(1.0percent); * 供试品杂质谱比较应注意的问题 一、方法的有效性 二、工艺与处方的差异性 三、样品的时效性 四、比较后说明什么 * 举例：盐酸胺碘酮注射液 原限度：杂质总量不得过0