Improved Mass Accuracy and Precision for Multi-Attribute Methods Using a New Internally Calibrated High Resolution Orbitrap Mass Detector,Analytical Chemistry

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Improved Mass Accuracy and Precision for Multi-Attribute Methods Using a New Internally Calibrated High Resolution Orbitrap Mass Detector
Analytical Chemistry ( IF 6.7 ) Pub Date : 2024-04-16 , DOI: 10.1021/acs.analchem.4c00520
Andrew W Dawdy ₁ , Edna A Trujillo ₁ , Zhenjiu Liu ₁ , Catharina Crone ₂ , Julia Kraegenbring ₂ , Kai Scheffler ₃

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In the development of biotherapeutics, a thorough understanding of a molecule’s product quality attributes (PQAs) and their effect on structure–function relationships and long-term stability is essential for ensuring the safety and efficacy of the product. First published in 2015, the multi-attribute method (MAM), based on LC-MS peptide mapping and automation principles, can be used to support biotherapeutic process and product development. The MAM provides simultaneous site-specific detection, identification, quantitation, and quality control monitoring of selected PQAs. In this article, a low-maintenance MAM-ready mass detector with a small footprint was evaluated for its ability to monitor PQAs on proteolytically digested proteins with high mass accuracy and precision. Optimized source parameters enable robust relative quantitation of attributes with high sensitivity and minimal in-source fragmentation. A combination of a built-in one-point mass calibration procedure prior to data acquisition and Scan-to-Scan on-the-fly mass correction allows monitoring of most peptides for at least 54 days with sub-1 ppm mass accuracies at high-resolution (180,000 at m/z 200). This enables the use of <3 ppm mass tolerances for peptide monitoring, supporting high method specificity and robustness. LC-MS based MAM data from this instrument compares well to data collected by earlier MAM systems and conventional HPLC profile-based drug substance release assays.

中文翻译：

使用新型内部校准高分辨率 Orbitrap 质量检测器提高多属性方法的质量准确度和精度

在生物治疗药物的开发中，彻底了解分子的产品质量属性（PQA）及其对结构功能关系和长期稳定性的影响对于确保产品的安全性和有效性至关重要。多属性方法 (MAM) 于 2015 年首次发布，基于 LC-MS 肽图谱和自动化原理，可用于支持生物治疗过程和产品开发。 MAM 可以对选定的 PQA 进行同步特定位点检测、识别、定量和质量控制监测。在本文中，评估了一种占用空间小的低维护 MAM 就绪质量检测器，以检测其以高质量准确度和精确度监测蛋白水解消化蛋白质的 PQA 的能力。优化的源参数能够以高灵敏度和最小的源内碎片对属性进行稳健的相对定量。数据采集之前的内置单点质量校准程序与扫描到扫描即时质量校正相结合，可以对大多数肽进行至少 54 天的监测，在高通量条件下质量精度低于 1 ppm。分辨率（180,000 at m / z 200）。这使得能够使用 <3 ppm 的质量公差进行肽监测，支持高方法特异性和稳健性。该仪器基于 LC-MS 的 MAM 数据与早期 MAM 系统和传统的基于 HPLC 曲线的药物释放测定收集的数据进行了很好的比较。

更新日期：2024-04-16

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