オーラルセッション
- 第4日 5月18日（金） 10:00～10:20 C会場（星雲2）
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4C-O1-P-1000 PDF
高分解能質量分析装置による抗体医薬の化学安定性評価
Monitoring chemical modifications of therapeutic antibodies such as oxidation and deamidation is essential because these modifications could affect biological efficacy and serum half-lives of agents. The primary structure of antibodies is typically confirmed by proteolytic digestion using enzymes such as trypsin, followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). This method, so-called ‘peptide mapping’, can provides almost 100% sequence coverage of the amino acid sequence thus we can reveal the positions which chemical modification occurs. The peptide mapping, however, has several disadvantages; sample preparation and data analysis are very time-consuming and sample preparation including proteolytic digestion process may cause the excessive modifications. To overcome these disadvantages, ‘subunit analysis’ of antibodies has been developed. Subunit analysis is performed by combination of a specific digestion with enzyme such as IdeS and LC-MS with high-resolution mass spectrometry, which provides information of sample heterogeneity including modifications. This rapid and simple analytical method can be useful to optimize the formulation of therapeutic antibodies. In this study, to evaluate the capability of subunit analysis method, we compared oxidation rate of therapeutic antibodies detected by conventional peptide mapping and subunit analysis. MS experiments were performed on an Q-TOF mass spectrometer, maXisII ETD (Bruker Daltonics).