Jordan Gregor, Onami Ichio, Heinrich Julia, Staack Roland F
Roche Pharma Research & Early Development (pRED), Pharmaceutical Sciences, Global DMPK & Bioanalytical R&D, Roche Innovation Center Munich, Nonnenwald 2, 82377 Penzberg, Germany.
Research division, Chugai Pharmaceutical Company, Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan.
Bioanalysis. 2017 Nov;9(21):1705-1717. doi: 10.4155/bio-2017-0158. Epub 2017 Sep 27.
Assessment of active drug exposure of biologics may be crucial for drug development. Typically, ligand-binding assay methods are used to provide free/active drug concentrations. To what extent hybrid LC-MS/MS procedures enable correct 'active' drug quantification is currently under consideration. Experimental & results: The relevance of appropriate extraction condition was evaluated by a hybrid target capture immuno-affinity LC-MS/MS method using total and free/active quality controls (QCs). The rapid extraction (10 min) provided correct results, whereas overnight incubation resulted in significant overestimation of the free/active drug (monclonal antibody) concentration. Conventional total QCs were inappropriate to determine optimal method conditions in contrast to free/active QCs.
The 'free/active analyte QC concept' enables development of appropriate extraction conditions for correct active drug quantification by hybrid LC-MS/MS.
评估生物制品的活性药物暴露情况对药物研发可能至关重要。通常，采用配体结合测定方法来提供游离/活性药物浓度。目前正在考虑混合液相色谱-串联质谱（LC-MS/MS）方法在何种程度上能够实现正确的“活性”药物定量。实验与结果：通过使用总质量控制品（QCs）和游离/活性质量控制品的混合靶向捕获免疫亲和LC-MS/MS方法，评估了合适提取条件的相关性。快速提取（10分钟）可提供正确结果，而过夜孵育则导致游离/活性药物（单克隆抗体）浓度显著高估。与游离/活性质量控制品相比，传统的总质量控制品不适用于确定最佳方法条件。
“游离/活性分析物质量控制品概念”能够为通过混合LC-MS/MS进行正确的活性药物定量开发合适的提取条件。
