摘要
目的建立一种基于半胱氨酸偶联方式的抗体偶联药物(antibody-drug conjugates,ADCs)抗CD30-vc-MMAE异质性分析的质控方法。方法本实验应用了分子排阻色谱(SEC-HPLC)、毛细管电泳(CE-SDS)以及实时成像毛细管等电聚焦电泳(iCIEF)等分析方法,对抗体偶联药物抗CD30-vc-MMAE的大小异质性和电荷异质性进行了分析。结果SEC-HPLC分析的纯度为(95.69±0.01)%;还原CE-SDS分析的纯度为(98.38±0.25)%,非还原CE-SDS可分离开6个主要峰,纯度之和为(97.82±0.44)%;和裸抗药物类似,iCIEF可有效的将酸区,碱区和主峰抗体进行较好地分离,主峰区的峰面积百分比为(43.52±2.03)%。结论初步建立了一种基于半胱氨酸偶联方式的ADC药物抗CD30-vcMMAE异质性分析的质控方法 ,为此类生物制品的质量控制提供参考。
OBJECTIVE To develop a heterogeneity analysis method of an antibody-drug conjugate （anti-CD30-vc-MMAE）. METHODS The size and charge heterogeneity of the antibody-drug conjugate （ anti CD30-ve-MMAE） was analyzed by SEC-HPLC, CE-SDS, and iCIEF. RESULTS The main peak purity was （95.69 ± 0. 01 ） % as shown by SEC-HPLC. The total peak purity of the heavy and light chains determined by reduced CE-SDS was （98.38 ± 0. 25% ）%. At non-reduced CE-SDS level, there were six main peaks, and the total purity of which was （97.82 ± 0.44） %. The acid modification, base modification, and main proportion could be separated effectively by iCIEF, and the peak area percentage of the main peak was （43.52 ± 2. 03 ） %. CONCLUSION A heteroge- necity analysis method of the antibody-drug conjugate （anti-CD30-vc-MMAE） has been preliminarily established and can provide reference for the quality control of this product.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2016年第13期1091-1095,共5页
Chinese Pharmaceutical Journal
基金
国家科技重大专项重大新药创制资助项目(2014ZX09304311-001)
中国食品药品检定研究院学科带头人培养基金资助项目(2013X3)
