Andrea F.G. Gargano

Reversed-phase LC–MS has limitations in numerous analytical applications. Alternative MS-compatible chromatographic techniques separate analytes in the liquid phase based on different retention mechanisms compared with reversed-phase LC. This article describes these alternative chromatographic approaches, relevant applications, and the future of these techniques.

In many applications, LC–MS approaches using HILIC, SFC, SEC, IEC, and HIC offer advantages over conventional reversed-phase LC–MS. The examples presented here should inspire you to consider these options for your analyses.

Clinical metabolomics requires analytical methods that provide both high resolution and high throughput. In this review, we assess the promise of a variety of techniques-including HILIC, SFC, multidimensional LC, ion-mobility mass spectrometry, and data-independent acquisition mass spectrometry methods-to meet those needs.