单抗N糖分析系统适用性对照品的建立

Establishment of System Suitability Standard for N-glycan Profile Analysis of Monoclonal Antibodies

目的建立单抗N糖分析方法的系统适用性对照品,并设定相应的系统适用性要求。方法利用液质联用(LC-MS)仪对N糖系统适用性对照品进行N糖型的表征鉴别,并对对照品进行稳定性评价。结合方法特点和验证数据,对系统适用性要求进行设定。结果建立的系统适用性对照品具有良好的稳定性,其糖型涵盖了单抗主要的N糖型种类。针对3种药典拟收录的单抗N糖分析方法,设定了以下系统适用性要求,包括:图谱与典型图谱相似、G1F(1,6)和G1F(1,3)的分离度应满足具体要求、G0F%应在规定的范围内、G0F保留时间的RSD应≤4%。结论建立了单抗N糖系统适用性对照品,可配合3种2020年版《中国药典》拟收录的N糖分析方法使用。

OBJECTIVE To establish the system suitability standard for N-glycan profile analysis of monoclonal antibodies.METHODS LC-MS was used to characterize the N-linked glycoform of the system suitability standard,and the stability was evaluated.The acceptance criteria of system suitability was set according to the method property and the data from method validation.RESULTS The data of accelerated and long-term stability test indicated that the system suitability standard was stable under storage condition.The N-glycoform of this standard was representative,which covered the main glycoform of monoclonal antibodies.The acceptance criteria of system suitability set for the three analytical METHODS were as below:the detected chromatogram should be visually similar to representative chromatogram;the resolution between G1F(1,6)and G1F(1,3),and G0F percentage should meet the specific requirements;the RSD of G0F retention time should be≤4%.CONCLUSION The standard substance for system suitability test and acceptance criteria for three N-glycan profile analytical METHODS are established.