Journal
RSC ADVANCES
Volume 12, Issue 16, Pages 9868-9882Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1ra08717g
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Funding
- National Key Research and Development Project [2018YFC1707300]
- National Natural Science Foundation of China [81973444, 81773875]
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In recent years, proteinic drugs, especially monoclonal antibodies, have become more important than small molecule drugs, and peptide mapping through LC-MS/MS has emerged as a new method for quality control. DI-MS/MSALL shows great potential as an alternative method for peptide mapping of proteinic drugs, with faster measurement time and lower solvent consumption.
In recent decades, proteinic drugs, in particular monoclonal antibodies, are taking the leading role of small molecule drugs, and peptide mapping relying on liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an emerging approach to substitute the role of a ligand-binding assay for the quality control of the proteinic drugs. However, such LC-MS/MS approaches extensively suffer from time-intensive measurements, leading to a limited throughput. To achieve accelerated measurements, here, the potential of DI-MS/MSALL towards tryptic peptide mapping was evaluated through comparing with well-defined LC-MS/MS means, and human serum albumin (HSA) was employed as the representative protein for applicability illustration. Among the 55 tryptic peptides theoretically suggested by Skyline software, 47 were successfully captured by DI-MS/MSALL through acquiring the desired MS2 spectra, in comparison to 51 detected by LC-MS/MS. DI-MS/MSALL measurements merely took 5 min, which was dramatically superior to the LC-MS/MS assay. Noteworthily, different from fruitful multi-charged MS1 signals for LC-MS/MS, most quasi-molecular ions received lower charged states. DI-MS/MSALL also possessed advantages such as lower solvent consumption and facile instrumentation; however, more sample was consumed. In conclusion, DI-MS/MSALL is eligible to act as an alternative analytical tool for LC-MS/MS towards the peptide mapping of proteinic drugs, particularly when a heavy measurement workload.
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