Pharmacokinetics of Quercetin and Other Flavonols Studied by Liquid Chromatography and LC-MS (a Review)

Abstract

Modern analytical methods used to study the pharmacokinetics of quercetin and other flavonols, i.e., biologically active compounds that exhibit various therapeutic properties, were reviewed. The preparation of biological fluids and tissues for analysis, chromatography conditions, and mass spectrometric detection for various flavonols as the aglycons and glycosides and their metabolites were discussed. Quantitative analyses of flavonol concentrations in biological samples and their mass spectrometric identification in in vitro and in vivo studies during tests with pure compounds and multi-constituent plant extracts were presented as typical examples.Keywords: quercetin, flavonols, flavonoids, flavonoid pharmacokinetics, bioanalytical methods, liquid chromatography-mass spectrometry (LC-MS/MS).Flavonols are a subclass of flavonoids, a varied and broad class of polyphenolic compounds that includes the flavonol quercetin, one of the most widely distributed and studied representatives. These compounds were well known over 100 years ago as plant pigments. However, the discovery in the 1990s of the antioxidant properties of flavonoids stimulated renewed interest in them. They are capable of neutralizing free radicals, which is responsible for their various therapeutic properties [1,2].A pharmacokinetic (PK) study in vivo in humans and experimental animals, i.e., absorption, distribution, metabolism, and elimination, is a necessary component of the evaluation of the mechanisms of possible therapeutic or toxic action of a biologically active compound. The PK parameters of drug candidates are related to the effectiveness and administration mode in order to establish the optimum concentrations.The properties of quercetin and other flavonols were briefly characterized and the development in the last decade of methods for determining the concentrations and identifying flavonols in biological media during PK studies were discussed in the review. Structure, properties and natural sources of flavonolsFlavonoids are secondary plant metabolites and share common biosynthetic pathways. They are responsible for the color of fruits and leaves. Surface tissues of plants are especially rich in them [3]. They are involved in the photosynthesis, proliferation, and death (through apoptosis) of plant cells. It is assumed that the main biological role of flavonoids is to protect plants from aggressive environmental factors (UV radiation, infectious agents).The variety of flavonoids is explained by the fact that most of them occur in plants as O-or C-glycosides. The aglycon is a 15-carbon skeleton, the principal elements of which are two aromatic rings joined by a pyran ring. The last determines to which subclass one flavonoid or another belongs. The classification includes the subclasses flavones, flavonols, flavanones (catechins), anthocyanidins, isoflavones, and flavanonols [4].

Electrospray ionisation mass spectrometric behaviour of flavonoid 5‐O‐glucosides and their positional isomers detected in the extracts from the bark of Prunus cerasus L. and Prunus avium L.

“…There is a large number of papers devoted to the analysis of flavonoid glycosides by using electrospray ionisation mass spectrometry (ESI‐MS), as summarised in many reviews 1–10 . One of the important structural information, which can be elucidated from collision induced dissociation (CID) ESI mass spectra of [M + H] + and/or [M − H] − ions is the site of glycosylation on the aglycone.…”