Iridoid Glycosides as Key Discriminators of Cranberry ( <i>Vaccinium macrocarpon</i> ) Cultivars Revealed by UHPLC-HRAM-MSn Metabolomics

BACKGROUND: Cranberry (Vaccinium macrocarpon) contains diverse hydrophilic phytochemicals, but their compositional profiles and cultivar-specific variation have not been comprehensively characterized. OBJECTIVE: The objective of this study was to profile hydrophilic metabolites in cranberry cultivars and identify constituents that differentiate among cultivars. METHODS: Water-eluted fractions of Sephadex® LH-20-separated cranberry extracts from six cultivars (Crimson Queen, Demoranville, Haines, Mullica Queen, Stevens, and Welker) were analyzed using ultra-high-performance liquid chromatography-high-resolution accurate-mass tandem mass spectrometry (UHPLC-HRAM-MSn). Metabolites were annotated based on accurate mass and MS2 fragmentation data and comparison with literature reports. Sparse partial least squares-discriminant analysis (sPLS-DA) was applied to assess classification performance and identify discriminative features. RESULTS: Thirty-nine putative hydrophilic metabolites were identified, including hydroxycinnamic acid hexose derivatives, anthocyanins, hydroxycinnamoylquinic acids, and a distinct group of iridoid glycosides. Vaccinoside and several coumaroyl-substituted monotropein derivatives were structurally characterized in cranberry for the first time. sPLS-DA identified iridoid glycosides as key discriminators, with higher abundance observed in the Welker cultivar. CONCLUSIONS: Cranberry cultivars contain previously unreported iridoid glycosides that contribute to chemotaxonomic differentiation. These results expand current knowledge of cranberry hydrophilic phytochemistry and support the relevance of iridoid glycosides as cultivar-informative metabolites.