Applications of low-flow LC–SRM for the analysis of large molecules in pharmaceutical R&D., (2014) Bioanalysis Vol. 6:13, pp 1859-1867. Michael E. Lassmen, Carmen Fernández-Metzler. Online publication date: July 2014.

Although ligand-binding assays are frequently employed to measure large molecules, the use of LC–SRM assays is increasingly popular due to the inherent selectivity advantage and the ability to operate without exquisitely selective antibodies. Until recently LC–SRM assays have been unable to compete with ligand-binding assays in terms of sensitivity. However, the use of low-flow chromatography prior to mass spectrometry has played a crucial role in increasing the sensitivity of LC–SRM platforms and enabling measurements of large molecules that had previously been unmeasurable. In this article, we highlight some technical advances, describe strategies for employing low-flow chromatography, and review recent literature that describes implementation of low-flow LC–SRM to support large-molecule analysis in pharmaceutical R&D.


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