Comprehensive two-dimensional liquid chromatography as a powerful tool for the analysis of food and food products

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Highlights

  • Recent achievements in comprehensive two-dimensional liquid chromatography are reported.

  • “Tailored” second dimension gradients are full of promise for orthogonality enhancement.

  • Modulation interfaces are constantly subjected to significant implementations.

  • Key aspects of applications to polyphenols, triacyglycerols and carotenoids are analyzed.

Abstract

Comprehensive two-dimensional liquid chromatography represents a valuable and powerful tool for the analysis of very complex samples. This review article illustrates how the coupling of two single LC “orthogonal” separations can be of valid aid for ensuring a deep chemical investigations of foods and food products. Specifically, in the first part, considerations about method optimization and novel modulation interfaces are reported whereas in the second part selected applications to polyphenols, lipids and carotenoids in various real-world samples are reported and discussed.

Introduction

Food analysis is the discipline dealing with the development, study and application of analytical procedures for the characterization of the properties of foods and their constituents. Such analytical procedures are used to provide information about a wide variety of different characteristics of foods, including their composition, structure, physicochemical properties and sensory attributes. This information is critical to our rational understanding of the factors that determine food properties, as well as to the ability to economically produce foods that are consistently safe, nutritious and desirable and for consumers to make informed choices about their diet. By far, HPLC, with its wide array of column materials and detectors has emerged as the most popular instrumental method for food analysis. Advanced detection systems capable of determining compounds from diverse chemical groups in one single analysis has rendered this technique as “unique”. To this regard, a stringent objective of food chemistry involves the continuous improvement and development of competitive and powerful analytical methodologies. However, when dealing with very complex food matrices, conventional liquid chromatography, despite a proper optimization protocol, is sometimes not sufficient and innovative analytical methods are considered as “mandatory”. A potential solution could be the employment of multidimensional liquid chromatography (MD-LC) techniques which involve the coupling of two or more independent (or nearly independent) stationary phases, taking into account the physical properties of compounds in the samples investigated. When, all the sample is going to be analyzed, the technique is called as “comprehensive” (LC × LC) [[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]] which has emerged as an innovative analytical method food analysis, as witnessed by the wide range of applications that can be found throughout the whole recent literature [[16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83], [84], [85], [86], [87], [88], [89], [90], [91], [92]]. A classification of the different LC × LC methods investigated with the chromatographic conditions and samples is reported in Supporting Information, Table S-1A for polyphenols [[16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70]], S-1B for tryacylglycerols (TAGs) and phospholipids (PLs) [[71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83], [84], [85], [86]] and S-1C for carotenoids [[87], [88], [89], [90], [91], [92]].

The objective of this review article is to make the food analytical chemist acquainted on general aspects of the LC × LC technique, followed by a section dedicated to its practical implementation, including the design of the latest interfaces, of interest especially for advanced readers. However it is worth mentioning that the fundamental aspects represent only part of the problems typically needed to be solved during the development of the LC × LC technique. A section is devoted to an overview of food “practical” applications which illustrate how the recent and future methodological developments could pave a way to new insights into the chemical composition of foods. Finally, as regards to nomenclature and terminology used here and pertinent to the LC × LC technique we employed the one proposed by Schoenmakers, Marriott and Beens in 2003, and updated in 2012 [93].

Section snippets

Why to use comprehensive two-dimensional liquid chromatography? Is any sample preparation necessary?

Food and food products are very complex mixtures containing many nutrients of organic and inorganic nature. Natural organic bio-actives represent secondary plant metabolites fundamental for the sensory and nutritional quality of fruits, vegetables and other plants. Although many achievements have been recently carried out in LC, e.g. superficially porous and monodisperse stationary phases, sub 2-μm, etc, conventional one-dimensional liquid chromatography (1D-LC) is in many cases incapable of

Method optimization

All LC × LC methods are the product of two 1D-LC experiments; thus, a careful selection of the individual 1D-LC separations is crucial when developing an LC × LC method. As a consequence, it is fundamental to understand the retention behavior of the analyte mixture in relation to the stationary phases that are intended to be investigated.

Polyphenols in beverages and plant extracts

Polyphenols are an essential part of the human diet and are widely distributed in nature. A particular attention has been paid in the last years due to their pharmacological properties e.g. the reduction of chronic diseases. Due to their enormous structural variety two kind of LC × LC platforms, namely RP-LC × RP-LC and HILIC × RP-LC have been employed for their analysis. Chronologically, RP-LC × RP-LC platforms with a “full gradient” approach has been the first to be investigated; however, in

Conclusions

Comprehensive two-dimensional liquid chromatography is gaining an ever growing popularity, due a potential wide range of successful applications, especially for the characterization of the properties of foods and their constituents. Great improvements have been recently poured into the development of novel interfaces aiming to solve somehow the decreased detection sensitivity and compatibility issues associated to conventional LC × LC applications. When the two separation dimensions are

CRediT author statement

Francesco Cacciola: Conceptualization, Writing-Original draft preparation, Writing- Reviewing and Editing, Supervision. Francesca Rigano: Conceptualization, Writing- Reviewing and Editing. Paola Dugo: Conceptualization, Writing-Reviewing and Editing. Luigi Mondello: Conceptualization, Writing-Reviewing and Editing, Supervision.

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