复孔分析是生物样品分析中配体结合分析(LBA)的标准操作方式,其目的是为了降低分析的变异性。随着分析仪器技术的进步和试剂质量的提升,特别是自动化应用,LBA的精密度得到显著提升,生物分析行业提出LBA是否也可以像LC-MS一样采用单孔分析。2019年3月发布的ICH M10(征求意见稿)已接受单孔分析的方式,目前已有多个行业组织或研究机构开展了单孔分析与复孔分析的对比研究,结果表明采用单孔分析并不显著影响毒代动力学(TK)和/或药代动力学(PK)关键参数、抗药抗体(ADA)的临界值以及灵敏度。本文总结现有文献的研究进展,提出单孔分析应用的技术要求,以期为单孔分析应用于TK/PK、以及ADA研究提供参考和借鉴,进一步促进药品注册技术标准与国际接轨。
Replicate analysis is the standard practice of ligand binding analysis(LBA) in bioanalysis, which is to reduce the variability of the analysis. With the progress of analytical instrument technology and the improvement of reagent quality, especially the automation application, the precision of LBA has been significantly improved, the bioanalysis industry is asking whether LBA could also be single-pore assayed as LC-MS. In recent years, ICH M10 (Draft for comment) has accepted the singlicate analysis, and several industry organizations or research institutions have carried out comparative studies of singlicate and replicate analysis. The results show that the use of singlicate analysis did not significantly affect the key parameters of toxicology kinetics(TK) and/or pharmacokinetics(PK), the critical values and sensitivity of anti drug antibody(ADA). This paper summarizes the research progress of existing literature, and propose the technical requirements of singlicate analysis application, in order to provide reference for the application of singlicate analysis in TK/PK and ADA study,and further promote the technical standards of drug registration in line with international standards.
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