Application of high-performance liquid chromatography with isotope-ratio mass spectrometry for measuring low levels of enrichment of underivatized materials.

Combining HPLC separations with an isotope-ratio mass spectrometric (IRMS) detection produces a device capable of measuring very low alterations in 13C abundance from analyte species that cannot be volatilized. Examples are presented showing proteins, carbohydrates, and nucleotides that are eluted from varying types of HPLC columns (reversed-phase, normal-phase, ion-exchange and size-exclusion). This wide range of chromatographic methods enables the analysis of compounds never before amenable to IRMS techniques and may lead to the development of many new assays.