Differentiation of flavonoid glycoside isomers by using metal complexation and electrospray ionization mass spectrometry

Abstract

The elucidation of flavonoid isomers is accomplished by electrospray ionization tandem mass spectrometry (ESI-MS/MS) via formation and collisional activated dissociation (CAD) of metal/flavonoid complexes containing an auxiliary ligand. Addition of a metal salt and a suitable neutral auxiliary ligand to flavonoids in solution results in the formation of [M(II) (flavonoid-H) ligand]+ complexes by ESI which, upon collisional activated dissociation, often result in more distinctive fragmentation patterns than observed for conventional protonated or deprotonated flavonoids. Previously, 2,2'-bipyridine was used as an auxiliary ligand, and now we compare and explore the use of alternative pyridyl ligands, including 4,7-diphenyl-1,10-phenanthroline. Using this technique, three groups of flavonoid glycoside isomers are differentiated, including glycosides of apigenin, quercetin, and luteolin.

Identification of isomeric flavonoid glucuronides in urine and plasma by metal complexation and LC‐ESI‐MS/MS

“…The use of auxiliary ligands in flavonoid glycoside/metal complexes has been shown to improve the sensitivity of analysis, 43 and the ligand itself plays a vital role in determining how the complex will dissociate. 21 Phenanthroline-based ligands have been fruitful in the past, so they were selected for the present application. Two different auxiliary ligands, 4,7-dmphen and 4,7-dpphen, formed complexes with the flavonoid glucuronides and cobalt(II) while also allowing isomer differentiation by CID.…”

Threshold dissociation and molecular modeling of transition metal complexes of flavonoids

“…Due to their acidic nature, flavonoids usually give higher ion abundances upon deprotonation in the negative ESI mode than via protonation in the positive ESI mode. Even greater ion abundances and more diagnostic fragmentation patterns of flavonoids have been reported based on a metal complexation mode in conjunction with CAD [10,[17][18][19]. Electrospray ionization of solutions containing a flavonoid, a transition metal salt, and an auxiliary ligand results in formation of complexes of the type [M II (flavonoid Ϫ H) auxiliary ligand] ϩ where M II is the transition metal ion.…”

“…Electrospray ionization of solutions containing a flavonoid, a transition metal salt, and an auxiliary ligand results in formation of complexes of the type [M II (flavonoid Ϫ H) auxiliary ligand] ϩ where M II is the transition metal ion. These complexes have allowed successful differentiation of flavonoid isomers [10,18,19], and the CAD patterns can be "tuned" via changing the auxiliary ligand [19]. However, little is known about the specific structures of the metal complexes, yet they have greatly facilitated isomer differentiation and thus merit further fundamental investigation.…”

Enhanced Detection and Structural Characterization of Flavonoids by Complexation with N,O-Bis(trimethysilyl)trifluoroacetamide Using Electrospray Ionization Mass Spectrometry

“…1 The flavonoids have aroused considerable interest recently because of their potential beneficial effects on human health; they have been reported to be antioxidants, antimicrobials, free radical scavengers, and metal chelators, and to have anti-allergic, anti-inflammatory, anti-tumor, anti-viral, and anti-bacterial properties. [2][3][4][5][6][7][8][9][10][11][12][13][14][15] Since flavonoids are an ubiquitous part of the human diet, their effects on human health are of interest. The study of health effects of flavonoids demands that sensitive methods be developed for their determination and quantifications.…”