定量一般指的是确定具体的数量,使用的方法需要能够准确确定具体的量,如HPLC等方法。杂质的定量试验可向原料药或制剂中加入已知量杂质进行测定。如果不能得到杂质,可用本法测定结果与另一成熟的方法进行比较,如药典方法或经过验证的方法。如不能测得杂质的相对响应因子,可在线测定杂质的相关数据,如釆用二极管阵列检测器测定紫外光谱,当杂质的光谱与主成分的光谱相似,则可釆用原料药的响应因子近似计算杂质含量(自身对照法)。并应明确单个杂质和杂质总量相当于主成分的重量比(%)或面积比(%)。
限度则是允许的最大值,测试时通常将样品测的结果与允许的最大值比较,样品测的结果不得大于允许的最大值。杂质限度测试可使用一些比较简便的方法,如标准比色法就是较便捷快速的杂质限度测定方法。
根据ICH相关指南中的描述,
- ICH Q3A(R2):Impurities in New Drug Substances
"An impurity is defined as any component of the new drug substance that is not the chemical entity defined as the new drug substance. Impurities may include starting materials, intermediates, degradation products, by-products, and reaction contaminants. Impurities can be classified into different categories, such as organic impurities, inorganic impurities, and residual solvents. The guideline provides recommendations on the qualification and control of impurities in new drug substances."
- ICH Q3B(R2):Impurities in New Drug Products
"This guideline addresses the identification, qualification, and control of impurities in new drug products. Impurities in drug products can arise from various sources, including the drug substance, excipients, and the manufacturing process. The guideline provides guidance on the reporting and qualification of impurities, as well as setting limits for specified, unidentified, and residual impurities in drug products."
杂质的定量是指我们精确测定药物样品中杂质的数量。通过这种定量分析,我们可以确定杂质在药物中的浓度。这有助于我们评估药物的纯度,并确定其是否符合质量标准。
杂质的限度是指在给定药物中允许的杂质含量的上限。限度是根据药物的使用情况、安全性要求和质量要求来确定的。它们通常基于临床经验、法规要求和毒理学研究等因素来制定。限度的目的是确保药物在使用过程中不会引起不良反应或对患者产生危害。
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