separations Review Advanced Analytical Approaches for the Analysis of Polyphenols in Plants Matrices—A Review Elena Roxana Chiriac 1, *, Carmen Lidia Chi¸ tescu 2, *, Elisabeta-Irina Geană 3 , Cerasela Elena Gird 1 , Radu Petre Socoteanu 4 and Rica Boscencu 1   Citation: Chiriac, E.R.; Chi¸ tescu, C.L.; Gean ˘ a, E.-I.; Gird, C.E.; Socoteanu, R.P.; Boscencu, R. Advanced Analytical Approaches for the Analysis of Polyphenols in Plants Matrices—A Review. Separations 2021, 8, 65. https://doi.org/10.3390/ separations8050065 Academic Editor: Ernesto Reverchon Received: 6 April 2021 Accepted: 10 May 2021 Published: 12 May 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia St., 020956 Bucharest, Romania; cerasela.gird@umfcd.ro (C.E.G.); rica.boscencu@umfcd.ro (R.B.) 2 Faculty of Medicine and Pharmacy, “Dunarea de Jos”, University of Gala¸ ti, 35 A.I. Cuza Str., 800010 Gala¸ ti, Romania 3 National Research &Development Institute for Cryogenics and Isotopic Technologies (ICSI Rm. Vâlcea), 4th Uzinei Street, 240050 Râmnicu Vâlcea, Romania; irina.geana@icsi.ro 4 “Ilie Murgulescu” Institute of Physical Chemistry, Romanian Academy, 202 Splaiul Independentei, 060021 Bucharest, Romania; s.radu@hotmail.com * Correspondence: roxana.elena.chiriac@gmail.com (E.R.C.); carmen.chitescu@ugal.ro (C.L.C.) Abstract: Phenolic compounds are plants’ bioactive metabolites that have been studied for their ability to confer extensive benefits to human health. As currently there is an increased interest in natural compounds identification and characterization, new analytical methods based on advanced technologies have been developed. This paper summarizes current advances in the state of the art for polyphenols identification and quantification. Analytical techniques ranging from high-pressure liquid chromatography to hyphenated spectrometric methods are discussed. The topic of high- resolution mass spectrometry, from targeted quantification to untargeted comprehensive chemical profiling, is particularly addressed. Structure elucidation is one of the important steps for natural products research. Mass spectral data handling approaches, including acquisition mode selection, accurate mass measurements, elemental composition, mass spectral library search algorithms and structure confirmation through mass fragmentation pathways, are discussed. Keywords: extraction; high-resolution mass spectrometry; fragmentation pathway; non-targeted analysis; chemical profiling 1. Introduction Plants have been used for centuries as remedies in several forms: unprocessed, as complex mixtures of different species as in Traditional Chinese Medicine [1], or, more recently, in commercial products as phyto-pharmaceuticals and dietary supplements [2–4]. The bioactivity of those natural products is generally high [4–6], supporting the high use of those products as a primary form of healthcare for a large part of the population [7]. Furthermore, about 80% of all synthetic drugs are directly or indirectly derived from them [8,9]. The pharmaceutical industry is currently showing an increasing interest in the development of new formulations with integrated vegetal extracts as a source of bioactive compounds [9]. Therefore, the assessment of the chemical components of herbs, spices or functional foods has become an essential part of our understanding. Polyphenols are secondary plant metabolites, and comprise a wide range of com- pounds that strongly differ in their structure, physicochemical and nutritional properties. Dietary polyphenols are one of the most important groups of natural antioxidants and chemopreventive agents in human diets, playing a vital role in supporting the functioning of biological systems [6,10]. Epidemiological, clinical and nutritional studies strongly sup- port the suggestion that polyphenolic compounds enhance human health by lowering risk and preventing several diseases and disorders [5,10]. It has been reported that polyphenolic Separations 2021, 8, 65. https://doi.org/10.3390/separations8050065 https://www.mdpi.com/journal/separations