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Review

Recent Trends in the Application of Chromatographic Techniques in the Analysis of Luteolin and Its Derivatives

by
Aleksandra Maria Juszczak
1,
Marijana Zovko-Končić
2 and
Michał Tomczyk
1,*
1
Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Białystok, ul. Mickiewicza 2a, 15-230 Białystok, Poland
2
Department of Pharmacognosy, University of Zagreb, Faculty of Pharmacy and Biochemistry, A. Kovačića 1, 10000 Zagreb, Croatia
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(11), 731; https://doi.org/10.3390/biom9110731
Submission received: 1 October 2019 / Revised: 7 November 2019 / Accepted: 8 November 2019 / Published: 12 November 2019
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
Browse Figure
Versions Notes

Abstract

:
Luteolin is a flavonoid often found in various medicinal plants that exhibits multiple biological effects such as antioxidant, anti-inflammatory and immunomodulatory activity. Commercially available medicinal plants and their preparations containing luteolin are often used in the treatment of hypertension, inflammatory diseases, and even cancer. However, to establish the quality of such preparations, appropriate analytical methods should be used. Therefore, the present paper provides the first comprehensive review of the current analytical methods that were developed and validated for the quantitative determination of luteolin and its C- and O-derivatives including orientin, isoorientin, luteolin 7-O-glucoside and others. It provides a systematic overview of chromatographic analytical techniques including thin layer chromatography (TLC), high performance thin layer chromatography (HPTLC), liquid chromatography (LC), high performance liquid chromatography (HPLC), gas chromatography (GC) and counter-current chromatography (CCC), as well as the conditions used in the determination of luteolin and its derivatives in plant material.

1. Introduction

Luteolin (Figure 1) is a yellow dye commonly found in fresh plants. It is a flavonoid of the flavone type that is distributed widely throughout the plant kingdom. Similar to other derivatives of 2-phenylbenzo-γ-pyrone, its basic skeleton has a characteristic C6-C3-C6 system, containing two benzene rings and a bridge with a C2-C3 double carbon bond and an attached oxygen atom [1,2,3,4]. Structure-activity studies have demonstrated that the pharmacological effects of luteolin and other flavonoids are strongly related to the presence of hydroxyl groups at the C5, C7, C3’ and C4’ carbons as well as to the presence of the double bond in the C2-C3 position [3,5]. The presence of the -OH group at position C3’ distinguishes luteolin from apigenin, and the lack of this group at the C3 carbon is an element that places luteolin in the flavone group [6].
Luteolin exhibits multiple biological effects such as antioxidant, anti-inflammatory and immunomodulatory activity. Plants rich in luteolin are often used in traditional medicine for treatment of various diseases such as hypertension, inflammatory disorders, and even cancer [7].
Because luteolin bears four hydroxyl groups (at the C5, C7, C3’ and C4’ positions), many derivatives of luteolin can be created. Various types of functional groups and/or sugar molecules can be attached to those positions, creating a huge number of different but structurally similar molecules. The most common are methyl derivatives, as well as C- and -O-glycosides [8,9].
Orientin, an 8-C-glucoside derivative of luteolin, displays an array of health-related biological properties, such as antioxidant, anti-ageing, antiviral, antibacterial, anti-inflammatory, vasodilatation, cardioprotective, radiation protective, neuroprotective, antidepressant-like, anti-adipogenesis, and antinociceptive effects. It may be found in different medicinal plants such as Ocimum sanctum (holy basil), Phyllostachys nigra (bamboo leaves), Passiflora sp. (passion flower), Linum usitatissimum (flax), Euterpe oleracea (Acai palm) and many others [10]. Another luteolin derivative, isoorientin (luteolin-6-C-glucoside) acts as an antioxidant, photoprotective [11], skin lightening [12], hepatoprotective [13] and anti-inflammatory agent [14]. O-glucosides of luteolin also display biological activities. For example, luteolin 7-O-glucoside alleviates skin lesions in murine models of atopic dermatitis [15] and protects cells against apoptosis induced by hypoxia/reoxygenation [16].
An increasing number of herbal preparations on the market contain luteolin and its derivatives, either as single-ingredient products or in mixtures with other phytochemicals, e.g., in form of medicinal plants extracts. To establish the quality of such products, it is important to use appropriate analytical methods. However, there is a lack of quality reviews of the available methods for quantification of luteolin derivatives, and the information on their comparison is lacking. Therefore, the aim of this article is to systematize knowledge and information in the field of chromatographic analytical techniques used for quantification of luteolin and its derivatives. The presented review is the first description of this type and provides a systematic overview of chromatographic analytical techniques including thin layer chromatography (TLC), high performance thin layer chromatography (HPTLC), liquid chromatography (LC), high performance liquid chromatography (HPLC), gas chromatography (GC) and counter-current chromatography (CCC), as well as the conditions used to assess luteolin and its derivatives.

2. Chromatographic Techniques for the Analysis of Luteolin Derivatives

Chromatography occupies a leading position among other instrumental methods in the analysis of chemical compounds. As a physicochemical method of separation and analysis of mixtures of chemical compounds, it allows detection and identification as well as quantitative determination of the test substance with high accuracy. The coupling of chromatography with other methods of analysis contributes to a more accurate detection and expansion of analytical capabilities, especially for complex mixtures of organic compounds [2,17,18].
Chromatographic techniques are based on the interaction of the mixture components with the mobile and stationary phases of the chromatographic system. This results in the division of the mixture components between the two phases. In addition, the interaction of the mobile and stationary phases is also important in the separation process [17,18]. According to the aggregation state of the mobile phase, chromatographic techniques are divided into gas, liquid and supercritical chromatography. Another criterion for classification of chromatographic techniques is the type of stationary phase. If the stationary phase is a liquid, the chromatography technique is referred to as partition chromatography. In the case of a solid, the technique is referred to as adsorption chromatography. Another example of the classification of chromatographic methods is their division depending on the chromatographic processing method. This classification allows distinguishing column chromatography and planar techniques, which include TLC and paper chromatography [17,19]. Many different chromatographic techniques are used in the analysis of luteolin derivatives. These include TLC, HPTLC, LC, HPLC, GC and CCC [19].

2.1. Thin Layer Chromatography in the Analysis of Luteolin Derivatives

Thin layer chromatography (TLC) is a rather simple but relatively popular method used in the analysis of flavonoids since 1960 [20]. It is a variation of LC that is carried out on a plane and is therefore referred to as planar chromatography. Despite the dynamic development of other chromatography techniques, TLC has not lost its importance in phytochemical analysis [18]. Its values are still recognized as is the basic tool in the qualitative analysis of natural products, and as such, it is still recommended by most modern Pharmacopoeias. In addition, the TLC technique is currently being improved, and the scope of its application is widening, while the results are becoming comparable to those obtained by GC or HPLC [20,21,22]. The stages of chromatographic analysis consist of placing the sample on the stationary phase and developing the chromatogram, followed by its visualization. In the final step, qualitative and/or quantitative determinations of the tested components are made [18,22,23]. General guidelines for flavonoid separation on TLC plates are presented in Table 1.
The main advantage of TLC is that it is a relatively simple and inexpensive technique that allows for rapid qualitative and quantitative analysis of the tested compounds. Samples analyzed with this method usually do not require pre-treatment, such as purification or concentration. In addition, several dozens of samples can be analyzed simultaneously on one plate. A large amount of the diluted sample can be applied to the stationary phase because the solvent evaporates during the application to the plate. Furthermore, due to the evaporation of the solvent phase after the development of the chromatogram, the detection method does not depend on the type of mobile phase used for separation. In TLC, it is possible not only to compare the analyzed components with the standards, but also to differentiate between substances bearing specific functional groups using the appropriate reagents for detection [18].
Thin layer chromatography and column chromatography (CC) are interchangeable techniques that may be combined, which significantly reduces costs and analysis time [22]. To achieve this, the same adsorbents are ideally used for both TLC and CC [18,22,24]. Nevertheless, other solvent systems may also be used. Elution in CC may be carried out in one mobile phase, or its composition may be changed during chromatography (mobile phase gradient), thereby increasing the elution force. In this case, the TLC mobile phase should be changed accordingly [18,24].
The type and quality of the stationary phase greatly affect the separation of mixture components. Thus, the selection of an appropriate adsorbent is very important. However, most TLC analyses are carried out in a normal phase system where hydrophilic (polar) adsorbents are used [18,23,24]. Reversed phase systems with lipophilic (non-polar) stationary phases are common and have little significance in the analysis of flavonoids [20]. Currently, the most commonly used stationary phase for the analysis of flavonoids is silica gel [20]. However, the use polyamide coated chromatography plates, in both normal and reversed phase systems, is not uncommon [24].
Detection of flavonoids on TLC plates is most often conducted under ultraviolet (UV) light at wavelengths of 254 or 366 nm. Luteolin derivatives also display fluorescence, which can be enhanced using the appropriate derivatization reagents, e.g., with the so-called NP/PEG reagent. The most frequent procedure consists of spraying the plate with 1% methanolic diphenylboric acid-β-ethylamino ester (natural product reagents, NP), followed by 5% ethanolic polyethylene glycol 4000 (PEG) solution [20]. A densitometer may also be used for the qualitative analysis of the substance. The analysis is performed by comparing the retardation factor (Rf) and absorption spectrum of the test substance and the standard. Analytes can also be identified by extracting the separated substances from the plate. Then, the analysis is carried out using Fourier transform infrared mass spectrometry (MS), UV spectrometry, Raman spectrometry or other techniques [23]. Even though TLC separation of luteolin derivatives (Table 2) can be performed in different types of stationary phases such as a polyamide phase [26,28], it is most frequently performed on silica gel plates that are often coated with a fluorescent indicator [27,29] (F254 plates) for preliminary detection. Such an approach has been used in case of analysis of luteolin 3’-O-glucoside, luteolin 6,8-C-dihexoside and luteolin 7-O-rutinoside in Phlomis sp. [27]. However, subsequent analysis with NP/PEG is the standard procedure for TLC analysis of luteolin [26,27,28,29], and it is almost always performed regardless of additional types of detection such as detection of flavonoids in Ligustrum vulgare with aniline phthalate [26]. Typically, the mobile phase for luteolin derivative separation consists of a mixture of aprotic organic solvents such as ethyl acetate (EtOAc) [26,28] or acetone (Ace) [29] and H2O with a significant amount of formic (FA) and/or acetic acid (AcOH) to avoid tailing of the separated zones [26,27,28,29].
Thin layer chromatography is often used as a complementary method to other chromatographic techniques. For example, analysis of the butanol (BuOH) fraction of the methanol (MeOH) extract from the leaves of the common privet (Ligustrum vulgare) conducted by Mučaji et al. [26] allowed isolation of two luteolin derivatives from the plant. TLC was carried out, among other techniques, on polyamide plates, and the optimal mobile phase was found. TLC was used for analysis of individual fractions obtained in column chromatography with or without acid hydrolysis of compounds. MS detection and nuclear magnetic resonance (NMR) spectra were also used [26]. Furthermore, TLC was used together with high performance liquid chromatography combined with mass spectrometry and pulsed amperometric detection (HPLC-PAD-MS) for analysis of luteolin and other phenolic compounds in Leontopodium alpinum. In addition to NP/PEG, UV, infrared (IR) and NMR analyses were used for identification of these compounds [29].
Compared to other chromatographic techniques, HPTLC results in reduced time and costs of analysis and provides much greater efficiency of separation. It is suitable even for the analysis of crude extracts similar to TLC, and a relatively small amount of solvent is used to analyze several samples, making this method environmentally friendly [60]. In the analysis of luteolin derivatives (Table 3), HPTLC silica gel 60 is almost exclusively used as the stationary phase [45,47,49,51], while HPTLC NH2 plates are rarely used, e.g., for separation of flavonoids in some Lamiaceae species such as Mentha piperita [53] and Thymus sp. [55]. In addition to NP/PEG (e.g., [52,57]), other detection systems may be employed for visualization of luteolin derivatives, such as bis-diazotized sulfanilamide [53] or aqueous solutions of Al3+ ions for flavonoids in M. piperita [53], honey [49] or Thymus sp. [55]. Similar to TLC, mixtures of organic solvents, H2O, and FA are most often used as the mobile phase [44,45,47,48,49,51,52].
High performance thin layer chromatography may also be used as a complimentary method to other chromatographic techniques. Chelyn et al. [44] used the HPTLC technique in the analysis of the ethanol (EtOH) extract of Clinacanthus nutans leaves. The analysis revealed the presence of, among others, luteolin 8-C-glucoside (orientin) and luteolin 6-C-glucoside (isoorientin) in the raw material. Their detection was conducted by comparing Rf coefficients using derivatization reagents and 366 nm UV light. In this work, the characteristic fluorescent bands after derivatization provided important clues for the identification of the major flavone present in the samples, while high performance liquid chromatography combined with ultraviolet spectrometry or a diode array detector (HPLC-UV/DAD) technique was employed for the simultaneous detection and quantification of these compounds [44].

2.2. High Performance Liquid Chromatography in the Analysis of Luteolin Derivatives

Among the many chromatographic methods, adsorptive chromatography, in which the mobile phase is liquid and the stationary phase is solid, is of the greatest practical importance. For example, this method has a much wider application than GC because it allows the analysis of substances in the form of liquids and soluble solids. Furthermore, it is also suitable for analysis of thermolabile substances because it is usually performed at low temperatures, and such samples are not degraded [61]. Due to the long analysis time, high mobile phase consumption and low efficiency, traditional CC is currently used mainly for preparative purposes. However, improved methods, such as HPLC and especially liquid chromatography combined with mass spectrometry (LC-MS), are increasingly used for analysis of natural compounds including luteolin derivatives [62].
High performance liquid chromatography has been performed since 1960. It is a dynamically developing method with a wide range of uses and has been proven to be very useful in phytochemical analysis. The principle of operation consists of pumping the mobile phase from the tank (or tanks) through the stationary phase-filled column. Eluents are previously filtered and degassed. Some systems are additionally equipped with thermostats that regulate the temperature of the column. If the chromatographic system is properly selected and applied, then the individual components are separated and detected. Strengthened signals are transmitted to the computer, where the obtained data are registered and properly processed [19]. The separation is based on competition of the molecules of the eluent and the substance being analyzed for the space on the adsorbent surface in the column [63,64].
When choosing a column, one should be guided by the size of the sample, time of analysis and expected effect of the separation. Although columns with different diameters are available, those with a diameter of 4.6 mm are by far the most common. However, due to better detection of the components separated in smaller diameter columns, these columns are increasingly being used for separation and analysis [19,63,65]. In addition, improved separation can be achieved using a column filled with smaller particles. In addition to 5 μm particles, which are most common, particles of 3 μm in diameter or even smaller can be used. For example (Table 4), this approach was chosen when separating luteolin 2’’-O-feruloylhexosyl-6-C-hexoside and luteolin 6-C-glucoside from Arenaria montana [66,67] and isoorientin in Achillea millefolium [68,69], as well as separating luteolin 6-C-hexosyl-8-C-pentoside, luteolin 2’’-O-deoxyhexosyl-6-C-glucoside and luteolin 6-C-glucoside in Cymbopogon citratus [70,71]. Particles less than 2 μm in diameter were used for ultra-performance liquid chromatography (UPLC) analysis of luteolin derivatives and other flavonoids in Lactuca sativa [72,73] and date palm (Phoenix dactylifera) [74].
Stationary phases with different polarity may be used in HPLC. In the normal phase system, polar column fillings are used, and most often the filling is silica gel. However, silica gel can adsorb water, which leads to the loss of the original separating properties of the column and thus to impaired reproducibility of the obtained results [19,65]. Therefore, the gel is often modified with the aim of enabling better separation of mixture components. This is performed mainly by bonding alkyl chains (or alkyl chains bearing other functional groups) to functional groups on the gel surface. Silica gels optimized in this way are referred to as the associated phase [2,65]. In the so-called reversed phase (RP) system, non-polar associated phases are used. Such systems are especially useful in the analysis of insoluble or poorly water-soluble compounds, as well as in the analysis of polar compounds, provided that a mobile phase with high water content is used. Typically, an octadecylsilane (ODS) phase, composed of 18 carbon atoms (RP-18), is employed. Such fillers can have different properties depending on the silica gel type and/or production method [19,65]. According to the available literature, the analysis of luteolin derivatives (Table 4) was performed exclusively with RP systems, and the RP-18 system was the most frequently used system, as exemplified in the separation of six luteolin derivatives in Securigera securidaca [75] or as many as ten derivatives in Capsicum annuum [76]. Stationary phases composed of 8 carbon atoms (RP-8) were rarely used. Examples include the separation of flavonoids in Coriandrum sativum [77] and Achillea millefolium [68,69].
The selection of an appropriate mobile phase is extremely important for chromatographic separation. The type of analyte, mixture composition, stationary phase and detector used should be taken into account. Mixtures of up to three components are most commonly used. In the reverse system, mixtures of MeOH/H2O or acetonitrile (ACN)/H2O are routinely used. As the amount of organic solvent increases, the retention time for non-polar substances decreases, while the addition of H2O extends their retention times. As a rule of thumb, systems containing ACN/H2O eluents are more efficient than those containing MeOH/H2O [19]. In the normal phase system, however, the base solvent is a non-polar eluent, and its polarity is appropriately modified by the addition of another solvent of higher polarity, e.g., chloroform (CHCl3) [65]. According to the available literature, virtually all mobile phases used for analysis of luteolin derivatives consisted either of ACN/H2O, e.g., [26,66,67,78] or, less often, MeOH/H2O mixtures [72,79,80,81]. Additionally, a modifier such as FA, e.g., [79,82,83,84], AcOH, e.g., [44,78,85,86,87], or trifluoroacetic acid (TFA) [88] was added to avoid peak tailing [89]. Analyses performed without acidic modifiers are rare [90].
In the chromatography process, the elution can be carried out in two ways. The first method is isocratic elution, which involves running with the same composition of mobile phase during the analysis. This means that a constant elution force is maintained throughout the entire separation period. In this case, even a slight change in the composition of the mobile phase may affect the results of the analysis. Isocratic elution is only rarely used for analysis of flavonoids. In the case of luteolin derivatives, this method was used only for analysis of luteolin 7-rhamnosyl- (1-6)-galactoside in Filago germanica [91], luteolin 7-rhamnosyl(1-6)galactoside in Galactites elegans [90], and various luteolin derivatives in Apium graveolens [80]. If the composition of the eluent changes during the division of the mixture, then the gradient elution can be described. The gradient can be linear or specifically programmed. With a change in the composition of the eluent, its elution force increases. For this reason, this method is used particularly for the separation of mixtures composed of substances of different polarity [2,64]. The vast majority of papers describing the separation of luteolin derivatives in plant mixtures use a gradient approach. Examples include the separation of luteolin 8-C-glucoside, luteolin 6-C-glucoside, luteolin 4’-O-glucoside and luteolin 7-O-glucoside from Chrysanthemum trifurcatum [92], thirteen luteolin derivatives from Cymbopogon citratus [70,71] and many others.
By far, the most common method for detection of luteolin derivatives is using diode array detectors (DADs) (also called photodiode array detectors, PDA), which were used in as many as 46 instances (e.g., for the analysis of luteolin derivatives and other flavonoids in Cymbopogon citratus [79], Dianthus versicolor [88], Clinacanthus nutans [44], Thymus alternans and others [93]). More often than not, however, DADs were combined with other detectors for additional structure determination or confirmation, with or without prior isolation. Examples of DADs combined with other detection methods for analysis of luteolin derivatives in plants include the use of tandem mass spectrometry (MS/MS) and NMR for Ligustrum vulgare [26], diode array detectors combined with electrospray ionization and mass spectrometry (DAD-ESI-MS) for Phoenix dactylifera [94] and Nerium indicum [95], electrospray ionization combined with tandem mass spectrometry (ESI-MS/MS) for Achillea moschata [96], electrospray ionization combined with time of flight mass spectrometry (ESI-TOF-MS) and electrospray ionization combined with ion trap and tandem mass spectrometry (ESI-IT-MS/MS) for Aloysia citrodora and many others.
For example, the HPLC-PAD-MS technique was used in the analysis of aerial flowering parts of the Edelweiss alpine region (Leontopodium alpinum). This method allowed the basic separation of almost all components of the L. alpinum extract prepared by exhaustive dichloromethane (DCM) followed by MeOH extraction. In total, 14 compounds have been isolated from the extract, including several luteolin derivatives. The authors used a gradient as the mobile phase as follows: H2O:0.9% FA:0.1% AcOH:1.5% BuOH (A) and ACN:30% MeOH:0.9% FA:0.1% AcOH (B) and MeOH (C). The structure of the isolated components was additionally confirmed using NMR spectroscopy [29].

2.3. Liquid Chromatography in the Analysis of Luteolin Derivatives

LC combined with tandem mass spectrometry (LC-MS/MS) (Table 5) is especially useful in the analysis of multicomponent mixtures, such as herbal extracts because it does not require a large amount of the sample or previous separation. To further reduce the influence of other factors on the analysis, more advanced techniques, involving the combination of more than one detection method, e.g., LC combined with NMR and MS (LC-NMR-MS), are increasingly used [139].
Research on ethanol extract from Lophatherum gracile stems and leaves was performed using LC coupled with MS/MS. Gradient elution was performed using 0.3% FA and MeOH. Analysis of the species revealed the presence of, among others, luteolin 7-O-β-D-glucoside, and luteolin 6-C-glucoside [140].
Another raw material containing luteolin and its derivatives is the cocoa seed (Theobroma cacao). In the analysis of the H2O:MeOH extract, the following mobile phase was used: H2O:0.1% FA and ACN:0.1% FA. The elution was carried out in a linear gradient, whereas LC combined with electrospray ionization and tandem mass spectrometry (LC-ESI-MS/MS) coupling allowed the identification of the tested compounds [141].
Lin and Harnly performed a water-methanol analysis of the flower extract of Chrysanthemum morifolium and distinguished many compounds, including numerous derivatives of luteolin. In this case, the mobile phase was a mixture of 0.1% FA:H2O and 0.1% FA:ACN, in varying proportions. The qualitative determination of the analyzed substances was based on a comparison of retention times as well as mass and UV/Vis spectra [142].

2.4. Gas Chromatography in the Analysis of Luteolin and Its Derivatives

Gas chromatography (GC) is a technique used to analyze volatile as well as non-volatile compounds after their derivatization. GC is characterized by chromatographic distribution of either a gas mobile phase on a solid adsorbent (gas-solid chromatography) or a liquid on an inert support (gas-liquid chromatography). GC can be hyphenated with various detection techniques such as GC combined with mass spectrometry (GC-MS), GC combined with tandem mass spectrometry (GC-MS/MS) or GC combined with time of flight mass spectrometry (GC-TOF-MS), thus greatly increasing the versatility, sensitivity and accuracy of the method [164,165]. The analyzed substances should be thermally stable, and their boiling (or sublimation) temperature should not exceed 350-400°C. To achieve this, non-volatile substances are often derivatived. Polar functional groups are transformed into their less polar counterparts, thus increasing the volatility of the prepared compounds. The most common examples include substitution with a trimethylsilyl (TM) group, organic radicals or compounds such as trimethylchlorosilane (TMCS), hexamethyldisilazane (HMDS) or N,O-bis(trimethylsilyl)-trifluoroacetamide (BSTFA). Such an approach greatly increases the number of possible analytes [2,17]. For example, phenolic groups of flavonoids are often transformed into their less polar trimethylsilyl counterparts allowing for rapid and effective separation of complex mixtures [166].
In adsorption GC, a gas that is chemically inert to the stationary phase as well as the components being analyzed is used as the mobile phase. Most often hydrogen, nitrogen or argon is used. Helium is being used less often due to its higher cost than other gases and the implementation of the principles of chemical safety. The mobile phase must be properly selected for compatibility with the detector used. However, the carrier gas itself does not have a significant influence on the separation effects of the analyzed mixtures [17]. In the process of separation, the method of application of the sample to the chromatography column is very important. The sample should always have as small of a volume and the shortest dosing time as possible. This ensures better separation and narrower bands [17,164].
Gas chromatography uses open-ended columns, i.e., capillary columns and packed columns. Open-ended (OT-open tubular) columns are characterized by much higher efficiency than packed columns; therefore, they are chosen much more often [164]. Capillary columns are particularly useful in the separation of substances with significantly different boiling points. Ideally, the column should have a similar polarity to the analyzed components. However, due to the higher efficiency and greater durability of stationary phases with low polarity, so capillary columns are recommended for chromatographic analyses [17,164].
Another factor that influences the efficiency of the separation of the analyzed sample components, as well as the time of analysis, is temperature. The separation temperature should be selected depending on the stationary phase used and the boiling point of the analytes [17,164].
The analysis of luteolin derivatives has been carried out in accordance with the general procedure used for analysis of other flavonoids (Table 6) [165]. MS was used for detection of volatile derivatives of luteolin, while the use of a flame ionization detector (FID) was described only in two papers [167,168]. Most commonly, helium was used as a carrier gas (e.g., [169,170,171]), but the use of nitrogen was also recorded [167,168]. The derivatization of luteolin, which is necessary for chromatographic separation, was mostly achieved with BSTFA/TCMS [170,171,172]. For the analysis of lipophilic luteolin derivatives, such as 7,3’,4’-trimethyl-luteolin in Arnica alpina, no derivatization was necessary [168].

2.5. Counter-Current Chromatography in the Analysis of Luteolin Derivatives

Counter-current chromatography (CCC) is a variation of liquid chromatography in which both the stationary and mobile phases are liquid. The separation of the constituents of the mixture is carried out in a system of immiscible liquids that are in equilibrium with each other. The method is simple and rapid, offering the possibility of introducing the raw sample to the column without need for previous clean-up [173]. Counter-current chromatography is mainly used for purification of natural compounds, while its use as an analytical technique is far less common. In CCC, various dividing techniques can be used, thus distinguishing centrifugal partition chromatography (CPC) and rapid- or high-speed CCC (HSCCC), often referred to as hydrodynamic chromatography [174,175]. High-speed CCC is particularly often encountered in studies involving the separation of flavonoids [176]. Table 7 presents the conditions for the separation of mixtures containing luteolin and its derivatives using rapid counter-current chromatography. Separation of luteolin derivatives from mixtures of different phytochemicals is usually carried out with mixtures of EtOAc with one of alcohol (BuOH, EtOH or AcOH) and H2O. Upon separation, structure determination by NMR is often necessary [173,177]. However, instead of NMR, high resolution mass spectrometry (HRMS) can also be employed for structure confirmation, as evidenced by the use of this technique for differentiation of various luteolin derivatives in Lippia origanoides [178].

3. Conclusions

The presented comparison of chromatographic methods currently used to determine luteolin and its derivatives provides a systematic summary of the available knowledge. Without a doubt, chromatographic analysis may be successfully employed as an efficient method for both qualitative assessment (fingerprinting) and quantitative determination of luteolin derivatives. In tedious and time-consuming determinations of multi-ingredient plant extracts, including those that contain the most prevalent luteolin derivatives, combinations of large-scale chromatographic techniques with serially aligned detection modalities such as LC-MS/MS or LC/NMR/MS were found to be particularly useful. Such beneficial coupling of chromatography with other analytic techniques expands analytical capabilities while additionally improving the accuracy, sensitivity, and precision of assays. Despite the dominant position of LC in the analysis of natural compounds and the dynamic development of novel chromatographic methods, the TLC/HPTLC has not lost its important place in the phytochemical analysis of luteolin derivatives. The technique is relatively simple and inexpensive while facilitating rapid qualitative and quantitative analysis of test compounds. In addition, it facilitates large quantities of diluted samples being deposited in the stationary phase, allowing for a wider choice of mobile phase carriers. The technique is subject to continuous improvements and its range of applicability is expanding.
Effective chromatographic analysis in the determination of luteolin derivatives requires appropriately selected chromatographic separation conditions. The appropriate choice of stationary phase sorbent may significantly improve test conditions. Most TLC analyses of luteolin derivatives are carried out in normal phase systems featuring a polar (hydrophilic) sorbent phase. In HPLC, separation conditions can be chosen more arbitrarily as the technique allows for the use of stationary phases of varying polarity which is particularly advantageous in the analysis of compounds that are either insoluble or poorly soluble in water. In order to additionally improve the sensitivity of HPLC analyses, one should focus on the column parameters responsible for appropriate separation. Quite often, the fairly successful analyses are used as starting points for further modifications, including the development of preparative-scale analyses.
Of all chromatographic techniques, GC is the least applicable in the analysis of plant extracts, including those that contain luteolin derivatives. Despite its high sensitivity and efficiency when coupled with various detection techniques (MS, MS/MS, TOF-MS), the chromatographic separation process involves high temperatures and derivatization of analytes. Due to this important aspect, GC-MS is less frequently used in the analysis of polyphenolic compounds.
The complexity of plant matrices is unquestionably a significant problem in the chromatographic analysis of plant extracts. It has a negative impact on the efficacy of analyses and prevents complete identification of all components of the plant extract. However, chromatography remains the primary and most effective analytical technique available in the current state of the art for the determination of compounds of natural origin.

Author Contributions

Conceptualization, M.T. and M.Z.-K.; literature investigation, A.M.J.; writing—original draft preparation, A.M.J., M.T., M.Z.-K.; writing—review and editing, A.M.J., M.T.; supervision, M.T., M.Z.-K.

Funding

The work was funded by the project № POWR.03.02.00-00-I051/16 from European Union funds, PO WER 2014-2020, grant №. 05/IMSD/G/2019.

Conflicts of Interest

All authors state that they are free of any conflicts of interest related to this paper.

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Biomolecules 09 00731 g001 550
Figure 1. Chemical structure of luteolin.
Figure 1. Chemical structure of luteolin.
Biomolecules 09 00731 g001
Table
Table 1. Recommended combinations of solvents / adsorbents for identification. of different flavonoid types by thin layer chromatography (TLC).
Table 1. Recommended combinations of solvents / adsorbents for identification. of different flavonoid types by thin layer chromatography (TLC).
Flavonoid TypeAdsorbent Type/Mobile Phase
CellulosePolyamideSilica gel
Polar flavonoid aglycones, e.g., flavonesBuOH:AcOH:H2O (3:1:1 v/v/v) a
CHCl3:AcOH:H2O (30:15:2 v/v/v) b		MeOH:AcOH:H2O
(18:1:1 v/v/v)		To:Py:FA (36:9:5 v/v/v)
Non-polar flavonoid aglycones, e.g., methylated flavones10–30% AcOH---CHCl3:MEOH (15:1 to 3:1 v/v)
Flavonoid glycosidesBuOH:AcOH:H2O (3:1:1 v/v/v) a
BuOH:AcOH:H2O (4:1:5 v/v/v) a		H2O:MeOH:MEK:methyl acetylacetone (13:3:3:1 v/v/v/v)EtOAc:Py:H2O:MeOH (80:20:10:5 v/v/v/v)
(especially flavone C-glycosides)
Abbreviations: AcOH, acetic acid; BuOH, butanol; CHCl3, chloroform; EtOAc, ethyl acetate; FA, formic acid; MeOH, methanol; MEK, methyl ethyl ketone; Py, pyridine; To, toluene. a The mobile phase is thoroughly mixed in the separating funnel and the upper phase is used. b The mobile phase is thoroughly mixed in the separating funnel and the excess water is discarded.
Table
Table 2. Thin layer chromatography in the analysis of luteolin derivatives.
Table 2. Thin layer chromatography in the analysis of luteolin derivatives.
Luteolin DerivativeStationary PhaseMobile PhaseDetectionAnalyzed SpeciesRef.
Luteolinsilica gel 60 F254Hx:EtOAc:AcOH (31:14:5 v/v/v);
To:DI:AcOH (90:25:4 v/v/v)		FBS;
UV, 254, 366 nm		Artemisia annua[25]
silica gel 60 RP-18 F254SFA:H2O:MeOH (5.5:47.25:47.25 v/v/v)
Luteolin 7-rutosidesilica gelEtOAc:FA:AcOH:H2O (100:11:11:23 v/v/v/v)NP/PEG, aniline phthalate;
UV, 254,366 nm
MS, NMR		Ligustrum vulgare[26]
cellulose30% AcOH
Luteolin 7-rhamnosidepolyamideCHCl3:MeOH:MEK:AcAc (9:4:2:1 v/v/v/v);
To:MeOH:MEK:BuOH (300:150:150:3 v/v/v/v)
Luteolin 3’-glucosidesilica gel 60 F254MeOH:H2O (15:5 v/v);
CHCl3:MeOH (15:5 v/v);
15% AcOH		NP/PEG;
UV, 366 nm		Phlomis persica[27]
Luteolin 6,8-dihexoside
Luteolin 7-rutinosidePh. elliptica
Luteolin 7-glucosidesilica gelEtOAc:FA:H2O (18:1:1 v/v/v)NP/PEG;
UV, 366 nm		Carduus acanthoides[28]
polyamide platesEtOAc:FA:AcOH:H2O (100:10:10:13 v/v/v/v)
Luteolinsilica gel 60 F254EtOAc:Ace:FA (8:1:1 v/v/v);
EtOAc:H2O:AcOH:FA (10:3:1:1 v/v/v/v)		NP;
UV, IR, NMR		Leontopodium alpium[29]
Luteolin 7,4’-diglucoside
Luteolin 6-hydroxy-7-glucoside
Luteolin 4’-glucoside
Luteolin 3’-glucoside
Luteolin 7-glucoside
Luteolinsilica gel 60 F254To:Et2O:AcOH (60:40:10 v/v/v);
EtOAc:AcOH:FA:H2O (100:11:11:26 v/v/v/v)		NP/PEG;
UV, 366 nm		Matricaria recutita, Achillea millefolium, Thymus vulgaris, Salvia officinalis[30]
Luteolin 7-glucoside
Abbreviations: AcAc, acetylacetone; Ace, acetone; AcOH, acetic acid; BuOH, butanol; CHCl3, chloroform; DI, 1,4-dioxane; Et2O, diethyl ether; EtOAc, ethyl acetate; FA, formic acid; FBS, Fast Blue B Salt; Hx, hexane; MeOH, methanol; MEK, methyl ethyl ketone; NP, 1% methanolic diphenylboric acid-β-ethylamino ester - natural product reagents; PEG, 5% ethanolic polyethylene glycol 4000; To, toluene; UV, ultraviolet spectroscopy; MS, mass spectrometry; NMR, nuclear magnetic resonance; IR, infrared.
Table
Table 3. High performance thin layer chromatography in the analysis of luteolin derivatives.
Table 3. High performance thin layer chromatography in the analysis of luteolin derivatives.
Luteolin DerivativeStationary PhaseMobile PhaseDetectionAnalyzed SpeciesRef.
LuteolinHPTLC silica gel 60 F254Hx:EtOAc:AcOH
(31:14:5 v/v/v);
To:DI:AcOH
(90:25:4 v/v/v)		FBS;
UV, 254, 366 nm		Artemisia annua[25]
HPTLC diol F254SCHCl3:Hx:EtOAc (34:4 v/v/v)2% AlCl3;
UV, 366 nm		Oxytropis glabra[31]
HPTLC silica gel 60
RP-18W		BuOH:MeOH:H2O
(300:50:50 v/v/v);
15% AcOH		NPR/PEG;
UV, 366 nm
HPTLC silica gel 60 F254EtOAc:MeOH:FA:H2O
(20:3:1:2 v/v/v/v)		MeOH:H2SO4
(95:5 v/v);
UV, 254, 366 nm		Asparagus racemosus,
Withania somnifera,
Vitex negundo,
Plumbago zylenica,
Butea monosperma,
Tephrosia purpurea		[32]
HPTLC silica gel 60 F254To:EtOAc:FA
(10:9:1 v/v/v)		UV, 254 nmCardiospermum halicacabum[33]
HPTLC silica gel 60 F254DCM:MeOH
(70:30 v/v)		UV, 254 nm;
NMR		Satureja montana[34]
HPTLC silica gel G60 F254To:EtOAc:FA
(6:4:1 v/v/v)		UV, 349 nmHygrophila spinosa[35]
HPTLC silica gel 60 F254EtOAc:MeOH:H2O:AcOH
(3:1:1:1 v/v/v/v)		UV, 254, 366 nmFoeniculum vulgare,
Cuminum cyminum,
Apium graveolens,
Petroselinum crispum,
Anethum graveolens,
Ammi majus		[36]
HPTLC silica gel 60 F254To:EtOAc:FA
(3:3:0.8 v/v/v)		MeOH:H2SO4
(90:10 v/v);
UV, 254 nm		Saraca asoca[37]
HPTLC silica gel 60 F254To:EtOAc:FA
(6:4:0.3 v/v/v)		NP/PEG;
UV, 366 nm		Premna mucronata[38]
HPTLC silica gel G60 F254To:EtOAc:FA
(10:9:1 v/v/v)		UV, 254, 366 nmAnisochilus carnosus[39]
HPTLC silica gel 60nHx:EtOAc:FA
(30:20:1.5 v/v/v)		NP/PEG;
UV, 349 nm		Satureja hortensis[40]
HPTLC silica gel 60 F254nHx:EtOAc:AcOH
(5:3:1 v/v/v)		UVPropolis[41]
HPTLC silica gel 60 GF254To:EtOAc:FA:MeOH
(3:3:0.8:0.2 v/v/v/v)		UV, 254, 365nmEclipta alba[42]
HPTLC silica gel 60 F254To:EtOAc:FA
(5:3:1 v/v/v)		NP;
UV, 366, 254 nm		Vitis vinifera[43]
Luteolin 6-glucoside
Luteolin 8-glucoside		HPTLC silica gel 60 F254EtOAc:FA:AcOH:H2O
(100:11:11:27 v/v/v/v)		NP/PEG;
UV, 366 nm		Clinacanthus nutans[44]
HPTLC silica gel 60 F254EtOAc:FA:H2O
(82:9:9 v/v/v)		NP/PEG;
UV, 366 nm		Passiflora alata,
P. edulis		[45]
Nano-DUASIL silica gel 60THF:To:FA:H2O
(16:8:2:1 v/v/v/v)		UV, 350 nmPhyllostachys pubescens[46]
Luteolin glucosideHPTLC silica gel 60 F254EtOAc:FA:AcOH:H2O
(100:11:11:26 v/v/v/v)		NP/PEG;
UV, 366 nm		Equisetum arvense[47]
HPTLC silica gel 60 F254EtOAc:AcOH:FA:H2O
(10: 1.1:1.1:2.6 v/v/v/v)		UV, 254, 366 nmAerva javanica[48]
LuteolinNP-HPTLC silica gel EtOAc:FA:AcOH:H2O
(100:11:11:27 v/v/v/v)		H2O solution of 4% Al2(SO4)3;
UV, 365 nm		Apis mellifera, honey[49]
To:EtOAc:AcOH
(50:45:5 v/v/v)
HPTLC silica gel 60 F254To:EtFo:FA
(6:4:1 v/v/v)		NP;
UV, 254, 366 nm		Potentilla grandiflora,
P. recta,
P. anserina,
P. fruticose,
P. rupestris,
P. thuringiaca		[50]
Luteolin 7-glucosidemodified HPTLC silica gel 60 F254 with CN, NH2To:EtFo:FA
(7:5:1 v/v/v)
HPTLC diol F254EtOAc:MEK:DIPE:FA
(3:10:4:1 v/v/v/v)
Luteolin 7-glucosideHPTLC silica gel 60EtOAC:DCM:AcOH:FA:H2O
(100:25:10:10:11 v/v)		NP;
UV, 366 nm		Lavandula stoechas[51]
HPTLC silica gel 60 F254EtOAc:AcOH:FA:H2O
(100:11:11:26 v/v/v/v)		NP/PEG;
UV, 254, 366 nm		Stachys sylvatica,
S. recta		[52]
Luteolin 7-rutinosideHPTLC NH2Ace:AcOH
(85:15 v/v)		MeOH:AlCl3 (98:2 v/v), bis-diazodized sulfanilamide;
UV-VIS, 365 nm
IR, MS, NMR		Mentha piperita[53]
HPTLC RP-18WH2O:MeOH
(60:40 v/v)
Luteolin 7-glucuronideHPTLC silica gel 60Et:Ace:H2O:FA
(55:25:10:10 v/v/v/v)		NP/PEG;
UV, 365 nm		Mentha piperita,
Melissa officinalis,
Salvia officinalis		[54]
Luteolin 7-glucosideHPTLC NH2Ace:AcOH (85:15 v/v)
Luteolin 7-rutinosideHPTLC NH2Ace:AcOH (85:15 v/v)MeOH:AlCl3 (98:2 v/v), NP/PEG;
UV, 365 nm		Thymus vulgaris,
Th. serpyllum,
Majorana hortensis,
Mentha piperita		[55]
Luteolin 7-glucoside
Luteolin 7-glucuronideAce:FA (85:15 v/v)[56]
HPTLC silica gel 60DIPE:Ace:H2O:FA (50:30:10:10 v/v/v/v)
LuteolinHPTLC silica gel 60 F254pre-develop: CHCl3:MeOH
(1:1 v/v);
nHx:EtOAc:FA
(20:19:1 v/v/v)		NP: white light, 254, 366, 330 nm;
PEG: 254, 297, 340, 366, 430 nm;
paraffin–nHx: 254, 320, 360, 366, 400 nm;
ESI-MS/MS		Rosmarinus officinalis[57]
Luteolin acetyl hexuronideSalvia officinalis
Luteolin 7-rutinoside
Luteolin acetyl hexoside
Luteolin hexuronide
Luteolin 3’,7-diglucosideHPTLC silica gel 60 F254EtOAc:MeOH:AcOH:FA:H2O
(30:1:2:1:3 v/v/v/v/v)		NP;
UV, 366 nm		Colocasia esculenta[58]
Luteolin 4’-glucoside
Luteolin 7-glucoside
Luteolin 8-glucoside
Luteolin 6-glucoside
Luteolin 8-glucosideHPTLC RP C18FA:MeOH:H2O
(0.5:6.65:2.85 v/v/v)		ESI-MS/MS,
254, 366 nm		Cyclanthera pedata[59]
HPTLC silica gel F254To:EtOAc:FA (6:5:1 v/v/v)
Abbreviations: Ace, acetone; AcOH, acetic acid; AlCl3, aluminium trichloride; Al2(SO4)3, aluminium sulfate; BuOH, butanol; CHCl3, chloroform; DCM, dichloromethane; DI, 1,4-dioxane; DIPE, diisopropyl ether; ESI-MS/MS, electrospray ionization combined with tandem mass spectrometry; EtFo, ethyl formate; EtOAc, ethyl acetate; Et, ether; FA, formic acid; H2SO4, sulfuric acid; Hx, hexane; MeOH, methanol; MEK, methyl ethyl ketone; nHx, n-hexane; NP, 1% methanolic diphenylboric acid-β-ethylamino ester - natural product reagents; neurotransmitters; PEG, 5% ethanolic polyethylene glycol 4000; THF, tetrahydrofuran; To, toluene; UV-VIS, ultraviolet-visible spectroscopy; ESI-MS, electrospray ionization combined with mass spectrometry.
Table
Table 4. High performance liquid chromatography/ultra performance liquid chromatography in the analysis of luteolin derivatives.
Table 4. High performance liquid chromatography/ultra performance liquid chromatography in the analysis of luteolin derivatives.
Luteolin DerivativeStationary Phase/ColumnMobile PhaseConditionsDetectionAnalyzed SpeciesRef.
LuteolinODS0.2% PA:H2O (A), MeOH (B)injection volume: 20 μL;
flow rate: 1.0 mL/min		DAD, 360 nmHoney[97]
ODS C180.2% PA:H2O (58:41 v/v)injection volume: 50 µL;
flow rate: 1.0 mL/min		UV, 350 nmChrysanthemum morifolium[98]
Kinetex C18ACN (A), 0.05% TFA:H2O (B)flow rate: 0.8 mL/minUV, 254 nmEnhalus acoroides[99]
ODS Hypersil C18MeOH:ACN (1.25:1 v/v) (A), 0.5% AcOH:H2O (B)flow rate: 0.8 mL/minMSPerilla frutescens[100]
Zorbax SB-C18PA:H2O pH 4.0 (A), ACN (B)injection volume: 50 µL;
flow rate: 0.6 ml/min; 25 °C		DAD, 330 nmVernonia condensata[101]
ODS C18MeOH (A), 0.05% TFA:H2O (B)injection volume: 20 μL;
flow rate: 1.0 mL/min		UV, 280 nmCorchorus olitorius[102]
RP0.5% PA:H2O (A), ACN (B)injection volume: 20 μL;
flow rate: 0.8 mL/min;
at 35 ℃		Triple-TOF-MSVeronicastrum latifolium[103]
RP C181% FA:H2O (A),
40% solvent A:ACN (B)		flow rate: 0.5 mL/min;
25 °C		DAD-ESI-MS/MSOlea europaea, olive oil[104]
Discovery HS C182% AcOH (A), ACN (B)injection volume: 20 μL;
flow rate: 0.8 mL/min		DAD
280, 320 nm		Agastache foeniculum[105]
Ultrasphere 5 C18H2O (A), ACN (B)injection volume: 10 μL;
flow rate: 1 mL/min; 25 °C		ESI-MS;
350 nm		Rosa rugosa[106]
Luteolin 6-glucosideVydac RP C180.05% TFA:H2O (A), 0.038% TFA:ACN (v/v) (B)injection volume: 10 μL
flow rate: 1 mL/min; 36 °C		UV, 342 nmFicaria verna[107]
Luteolin 8-glucosideRP C180.5% FA:H2O (A), ACN (B)injection volume: 20 µL;
flow rate: 0.5 mL/min;
23 °C		DAD, 254, 340 nmJatropha gossypiifolia, J. mollissima[108]
Luteolin 7-glucosideHypersil gold C180.1% FA:H2O (A), 0.1% FA:MeOH (B)injection volume: 10 µL;
flow rate: 0.35 mL/min;
38 °C		MSRhoeo discolor[109]
Thermo C180.3% FA:H2O (A), ACN (B)injection volume:10 μL;
flow rate: 1.0 mL/min;
30 °C		DAD-Q-
Orbitrap-MS		Epimedium brevicornum,
Anacyclus pyrethrum,
Lycium barbarum,
Cuscuta australis		[110]
LuteolinEclipse XDB C180.025% AcOH:H2O (A), 5% Ace:ACN (B)30 °CESI-MS/MSOlea europaea, olive oil[111]
Luteolin 7-glucosideEclipse XDB C181% PA:H2O (A), ACN (B)injection volume: 10 μL;
flow rate: 1 mL/min; 25 °C		DAD-ESI-QTOF-MS/MSVerbascum ovalifolium[112]
Luteolin 7-rutinosideEclipse XDB C18ACN (A), 0.2% FA (B)flow rate: 0.3 mL/min;
30 °C		DAD, 230, 254, 290, 334 nm;
MS/MS; NMR		Ligustrum vulgare[26]
Luteolin 7-rhamnoside
LuteolinGemini C180.5% AcOH:H2O (A), ACN (B)25 °CESI-QTOF-MSOlea europaea[78]
Luteolin 7,4-diglucoside
Luteolin 7-rutinoside
Luteolin 4-glucoside
Luteolin 3-glucoside
Luteolin 7-glucoside
Luteolin 6-glucosideSpherisorb S5 ODS-25% FA:H2O (A), MeOH (B)flow rate: 1 mL/minDAD, 280 nmCymbopogon citratus[79]
Luteolin 7-rhamnoside
Luteolin 7-glucoside
Luteolin 6-glucosyl-8-arabinoside
Luteolin 2’’-feruloylhexosyl-6-hexosideSpherisorb S3 ODS-2 C180.1% FA:H2O (A), ACN (B)flow rate: 0.5 mL/min;
35 °C		DAD-MS;
280, 370 nm		Arenaria montana[66,67]
Luteolin 6-glucoside
LuteolinKinetex 100 C181% FA:H2O (A), 1% FA:ACN (B)flow rate: 1 mL/min; 30 °CESI-QTOF-MS;Rosmarinus officinalis[82]
Luteolin 7-rutinoside
Luteolin 3-glucuronide
Luteolin 3’-(2’’-acetyl)-glucuronideSuperschera 100 RP C18DAD, 324 nm
Luteolin 6-hydroxy-7-glucoside
Luteolin hexosyl-hexoside-malylesterAquasilW C18TFA solution (pH 2.8) (A), ACN (B)flow rate: 1.0 mL/min;
15 °C		UV/DAD, 340 nmDianthus versicolor[88]
Luteolin 6-glucosyl-7-galactoside
Luteolin 6-glucosyl-7-rutinoside
Luteolin 6-glucosyl-7-rhamnosyl-galactoside
Luteolin 7-apiofuranosyl (1→2)-glucopyranosideEclipse Plus C180.1% FA:MeOH (A), 0.1% FA:H2O (B)injection volume: 10 μL;
isocratic mixture flow rate: 0.3 mL/min		QTOF-MS/MSApium graveolens[80]
Luteolin 7-glucopyranoside
Luteolin 7-[apiofuranosyl (1→2)-(6’’-malony)]-glucopyranoside
Luteolin 7-(6-rhamnosyl)hexosideKinetex C181% FA (A), ACN (B)injection volume: 8 μL;
flow rate: 0.8 mL/min		DAD-ESI-MS; 340 nmPhoenix dactylifera[94]
Luteolin 7-(2-rhamnosyl)hexoside
Luteolin 7-(2-hexosyl[6-sulfate])hexoside
Luteolin 7-hexosyl(6-sulfate)
LuteolinGemini C180.1% FA:H2O (A), 0.1% FA:ACN (B)0-60 min, 10–60% B;
flow rate: 1 mL/min		DAD-ESI-MS/MS;
210, 270, 310 and 350 nm		Achillea moschata[96]
Luteolin 7-glucoside
Luteolin 7-glucosideSynergy Polar RP 80Å,
LiChroCART 4-4 with guard column LiChrospher 100 C18		0.9% FA:0.1% AcOH:1.5% BuOH:H2O (A),
30% MeOH:0.9% FA:0.1% AcOH:ACN (B),
MeOH (C)		injection volume: 5 μL;
flow rate: 1.0 mL/min;
45 °C		PAD;
MS;
UV;
IR;
NMR		Leontopodium alpium[29]
Luteolin 7,4’-diglucoside
Luteolin 6-hydroxy-7-glucoside
Luteolin 4’-glucoside
Luteolin 3’-glucoside
Luteolin 7-diglucuronideEclipse Plus C181% FA:H2O:ACN (A), ACN (B)injection volume: 20 μL;
flow rate: 0.5 mL/min		DAD; UV-VIS, 190-450 nm;
ESI-TOF-MS;
ESI-IT-MS/MS		Lippia citrodora[113]
Luteolin 5-rutinosideLuna C180.1% FA:H2O (A), ACN (B)injection volume: 5 μL;
flow rate: 1.0 mL/min		DAD, 200-400 nm;
ESI-MS		Nerium indicum[95]
Luteolin 7-rutinoside
Luteolin diglucosideLuna C181% FA:H2O (A), ACN (B)injection volume: 20 μL;
flow rate: 1 mL/min		PDA-ESI-MS/MSTaraxacum officinale[114]
Luteolin 7-rutinoside
Luteolin 7-glucoside
LuteolinGemini RP C182% AcOH:H2O (A), ACN (B)---ESI-MS;
257, 278 and 340 nm		Pistacia atlantica[85]
Luteolin 2’’-Galloyl-4’-glucoside
Luteolin 4’-glucoside
Luteolin 6-methoxy-8-arabinosyl-7-glucosideSymmetry Shield Waters RP180.2% FA:H2O (A), ACN (B)flow rate: 1.2 mL/minUV/PAD-MS; UV;
200–600 nm		Saccharum officinarum[115]
Luteolin 8-glucosideSymmetry Shield RP18UV/PAD
Luteolin 8-rhamnosyl-7-rhamnoside
Luteolin 8-glucosideKinetex PFP0.8% AcOH:H2O (A),
ACN (B)		injection volume: 10 μL;
flow rate: 0.7 mL/min;
40 °C		UV/DAD, 330 nmClinacanthus nutans[44]
LuteolinEclipse XDB C18MeOH (A), 0.2% FA:H2O (B)flow rate: 0.8 mL/min;
30 °C		DAD-MS/MS;
UV;
254, 360 nm		Securigera securidaca[75]
Luteolin 7-glucoside
Luteolin 7-glucuronyl-3-glucoside
Luteolin 6-glucoside
Luteolin 6-glucosyl-2’’-rhamnoside
Luteolin 6-glucosyl-4’-glucoside
Luteolin 3’-glucoside
Luteolin hexosyl-rhamnosideSpherisorb S3 ODS-2 C80.1% FA:H2O (A), ACN (B)flow rate: 0.5 mL/min;
35 °C		DAD-MS;
280, 370 nm		Coriandrum sativum[77]
Luteolin 7-rutinoside
Luteolin 7-glucoside
LuteolinXDB C181% FA:H2O (A), ACN (B)injection volume: 100 µL;
flow rate: 4 mL/min		NMR;
MS		Casimiroa edulis[116,117]
Luteolin 6-glucosyl-8-arabinoside
Luteolin 7-glucoside
Luteolin 6-arabinosyl-8-glucoside
Luteolin 3-glucopyranosidePLRP-S 100Å0.1% FA:H2O (A), ACN (B)injection volume: 100 µL;
flow rate: 1.5 mL/min		MSThymus alternans[93]
Luteolin 7-glucopyranoside
Luteolin 7-rutinoside
Luteolin methoxy-hexoside
Luteolin 4’-glucopyranosideXDB C181% FA:H2O (A), ACN (B),injection volume: 100 µL;
flow rate: 4 mL/min
Luteolin 6-hydroxy-7-glucosideGemini C180.1% FA:H2O (A),
ACN (B)		flow rate: 0.8 mL/minUV-VIS, 200-400 nm;
MS;
DAD;
NMR		Athrixia phylicoides[118]
LuteolinSyncronis C180.1% AcOH:H2O (A), ACN (B)injection volume: 5 μL;
flow rate: 0.3 mL/min		DAD-MS/MSHoney[86]
Luteolin 7-rhamnoside
LuteolinHSS T30.1% FA:H2O (A), 0.1% FA:ACN (B)injection volume: 3.1 µL;
flow rate: 0.15 mL/min		PDA-MSPhoenix dactylifera[74]
Luteolin rhamnosyl hexoside
Luteolin rhamnosyl dihexoside
Luteolin diglucuronideS3 ODS-2 C180.1% FA:H2O (A), ACN (B)flow rate: 0.5 mL/min;
35 °C.		DAD-ESI-MS;
370, 330 and
280 nm		Thymus pallescens, Saccocalyx satureioides,[119,120]
Luteolin 7-glucuronide
Luteolin 7-rutinoside
Luteolin 7-glucoside Ptychotis verticillata
Luteolin 6-glucosideColeostephus myconis
LuteolinKinetex C18ACN (A), 0.1% FA:H2O (B)injection volume: 10 μL;
flow rate: 0.4 mL/min		ESI-MSLathyrus pratensis[121]
Luteolin rutinoside
Luteolin hexoside
Luteolin 6-hexosideL. aureus
Luteolin 7-glucosideLuna C185% FA:H2O (A), MeOH (B)injection volume: 100 µL;
flow rate: 1 mL/min; 35 °C		DAD, 200, 600 nmThymus pulegioides[81]
Luteolin hexuronide0.1% FA:H2O (A), MeOH (B)injection volume: 10 µL;
flow rate: 0.5 mL/min;
40 °C		ESI-MS/MS
LuteolinEclipse Plus C180.5% AcOH:H2O (A), ACN (B)injection volume: 5 µL;
flow rate: 0.5 mL/min		DAD-QTOF-MS;
325-371 nm		Ficus carica[87]
Luteolin hexosyl-pentoside
Luteolin 6-glucoside
Luteolin 8-glucoside
Luteolin 7-glucoside
Luteolin (3-hydroxy-3-methylglutaroyl)-X’’-deoxyhexosyl-hexosideODS-2 C18 with ODS-2 C18 guard cartridge1% FA:H2O (A), MeOH (B)flow rate: 0.2 mL/min;
25 °C		PDA-ESI-MSUrtica membranacea[122]
Luteolin 6-hexoside
Luteolin 6-rutinoside
Luteolin dihexoside
LuteolinSyncronis C180.01% AcOH:H2O (A), ACN (B)inaction volume: 5 μL;
flow rate: 0.25 mL/min		MSCapsicum annuum[76]
Luteolin 6,8-dihexoside
Luteolin 6-hexosyl-8-pentoside
Luteolin 6-pentosyl-8-hexoside
Luteolin 6-hexoside
Luteolin 8-hexoside
Luteolin 7-(2’’-pentosyl-4’’-hexosyl)hexoside
Luteolin 7-(2’’-pentosyl)hexoside
Luteolin 7-glucoside
Luteolin 7-[2’’-(5’’’-sinapoyl)pentosyl]hexoside
Luteolin 7-(2’’-pentosyl-4’’-hexosyl-
6’’-malonyl)hexoside
Luteolin 7-(2’’-pentosyl-6’’-malonyl)
hexoside
Luteolin 7-[2’’-(5’’’-sinapoyl)pentosyl-
6’’-malonyl]hexoside
LuteolinPurospher star C1810% FA:H2O (A),
ACN (B)		25 °CDAD-ESI-MS;
320-280 nm		Citrus aurantifolia[123]
Luteolin 6,8-diglucoside
Luteolin 8-glucoside
Luteolin 7-rutinoside
LuteolinZorbax SB-C18AFNH4:H2O:ACN:FA (A), AFNH4:H2O:ACN:FA (B)injection volume: 5µL;
flow rate: 1.0 mL/min		ESI-MS;
325 nm		Caucalis platycarpos[124]
Luteolin 7-glucoside
Luteolin 7-rutinoside
Luteolin 7-glucosideBeta-Basic C185% FA:ACN (A); 5% FA:H2O (B)injection volume: 20 µL;
flow rate: 0.9 mL/min		UV, 280 nmMelissa officinalis[54]
Luteolin 7-glucuronideMentha piperita,
Salvia officinalis
Luteolin 7-rutinoside
Luteolin
Luteolin 7-glucuronide
Luteolin 7-rhamnosyl-hexoside
Luteolin 7-rutinoside
Luteolin 7-glucoside
Luteolin 7-glucuronide
Luteolin 7-rutinoside
Luteolin diglucoside		UPLC BEH C18 and a Acquity UPLC BEH C18 VanGuardTM pre-column0.1% AcOH:H2O (A),
0.1% AcOH:MeOH (B)		injection volume: 5 µL;
flow rate: 0.5 mL/min		DAD-ESI-QTOF-MS;
370 nm		Lactuca sativa[72]
HSS T30.1% FA:H2O (A), 0.1% FA:ACN (B)injection volume: 3 µL;
flow rate: 0.4 mL/min		IMS-QTOF-MS[73]
Luteolin hexosideHypersil Gold C180.1% FA:H2O (A), ACN (B)---DAD-ESI-MSSalvia elegans,
S. greggii,
S. officinalis		[125,126]
Luteolin hydroxy-glucuronide
Luteolin 7-glucoside
Luteolin 7-glucuronide
Luteolin malonyl-hexoside
Luteolin glucuronide
Luteolin glucosideflow rate: 0.2 mL/minThymus barona,
T. pseudolanuginosus,
T. caespititius		[126]
Luteolin rutinoside
Luteolin 7-rhamnosyl(1-6)galactosideEclipse XDB-C180.1% FA:H2O (A), 0.1% FA:ACN (B)flow rate: 0.5 mL/min;
25 °C		MSFilago germanica[91]
Luteolin 4’-glucuronideC18μ-Bondapak RP18MeOH:H2O (42:58 v/v)flow rate: 2.0 mL/minNMRGalactites elegans[90]
LuteolinKinetex 100 A C181% FA:H2O (A), ACN (B)injection volume: 5 µL;
flow rate: 0.8 mL/min;
25 °C		DAD, 340 nmAllophylus africanus[83,127]
Luteolin 3’-7-diglucoside
Luteolin 7-glucoside
Luteolin 6-(2-rhamnosyl)-hexosideDAD-ESI-MS/MS;
280, 340 nm
Luteolin (pentosyl)-hexoside
Luteolin hexoside
Luteolin 6-glucosideODS2 C80.1% FA:H2O (A), ACN (B)flow rate: 0.5 mL/min;
35 °C		DAD-ESI-MS;
280, 370 nm		Achillea millefolium[68,69]
Luteolin 6-hexosyl-8-pentosideS3 ODS-2 C180.1% FA:H2O (A), ACN (B)flow rate: 0.5 mL/min;
35 °C		DAD-MS;
280, 370 nm		Cymbopogon citratus[70,71]
Luteolin 2’’-deoxyhexosyl-6-glucoside
Luteolin 6-glucoside
Luteolin 6-pentosyl-8-pentoside
Luteolin-7-rhamnoside
Luteolin 7-glucoside
Luteolin 2’’-deoxyhexosyl-pentoside
Luteolin 6-pentoside
Luteolin 2’’-deoxyosyl-6-(6-deoxy-
pento-hexosuloside
LuteolinC180.005 % FA:H2O (A), MeOH (B)injection volume: 10 µL;
flow rate: 0.5 mL/min;
30 °C		MS-OrbitrapChrysanthemum trifurcatum[92]
Luteolin 8-glucoside
Luteolin 4’-glucoside
Luteolin 7-glucoside
Luteolin 6-glucoside
Luteolin 6-glucosideHSS T30.1% FA:H2O (A), 0.1% FA:ACN (B)injection volume: 3.1 μL;
flow rate: 0.15 mL/min		PDA-MSPassiflora edulis[128]
Luteolin 8-glucoside
Luteolin 6-deoxyhexosyl-8-pentoside
Luteolin 6-fucoside
Luteolin 8-deoxyhexoside
Luteolin 6,8-diglucoside
Luteolin 6,8-diglucosideKinetex C180.05% FA:H2O (A), 0.05% FA:ACN (B)flow rate: 0.4 mL/min;
40 °C		MS/MSEragrostis tef[84]
Luteolin 8-glucosyl-7-glucoside isomer
Luteolin 6-glucosyl-7-glucoside isomer
Luteolin 8-glucosyl-7-rhamnoside
Luteolin 8-glucoside
Luteolin 7-glucoside
Luteolin 7-rhamnoside
Luteolin 7-(6’’-syringly)glucosyl-6-glucoside
Luteolin 7-(2’’-syringyl)arabinosyl-6-glucoside
Luteolin 8-(6’’-diacetyl)glucoside
LuteolinNucleosil 100-3.5 C18FA:H2O (A), FA:ACN (B)injection volume: 20 µLMSArum hygrophilum[129]
Luteolin 6-glucoside
Luteolin 6-[6’’-glocosy-caffeoyl-glucopyranosyl(’’→2)-glucopyranosideEclipse Plus C180.2% FA:H2O (A), 0.2% FA:ACN (B)30 °CPDA-ESI-MS/MSTriticum aestivum[130]
Luteolin 6-glucopyranosideUV, 350 nm
Luteolin 7-glucosideSyncronis C180.1% FA:H2O (A), ACN (B)injection volume: 5 μL;
flow rate: 0.25 mL/min		MS/MSIris pumila,
I. variegata,
I. humilis		[131]
Luteolin 6-glucoside
Luteolin 7-(2’’-p-coumaroyl)-rhamnoside
LuteolinLuna Omega Polar C18 with Polar C18 Security Guard cartridge0.1% FA:H2O (A), ACN (B)flow rate: 0.4 mL/minESI-MS/MS;
320, 350 nm		Parentucellia latifolia[132,133]
Luteolin hexoside
LuteolinIntersil ODSACN:H2O:FA (10:89:1 v/v/v) (A),
ACN:H2O:FA (89:10:1 v/v/v) (B)		injection volume: 10 µL;
flow rate: 0.5 mL/min;
40 ℃		DAD-MS/MS;
360 nm		Verbascum eskisehirensis[134]
Luteolin glucoside
Luteolin glucuronide
Luteolin pentosyl-glucoside
Luteolin 4’-glucosideKinetex RP C18PA:H2O pH 3 (A), PA:ACN pH 3 (B)injection volume: 1 µL;
flow rate: 1.2 mL/min; 35 ℃		UV
300 nm		Matricaria recutita[135]
Luteolin 7-O-glucuronideC180.02% TFA:H2O (A),
MeOH:ACN (3:7 v/v) (B)		injection volume: 2.5 µL;
flow rate: 0.9 mL/min; 45 °C		DAD-ESI-MS
240, 254, 325 nm		Lippia alba[136]
Luteolin glucosideYMC-Triart C180.1% FA:H2O (A), 0.1% FA:ACN B)injection volume: 10 µL;
flow rate: 0.8 mL/min		DAD-ESI-MA
265, 280, 330, and 360 nm		Chrysanthemum morifolium[137]
Luteolin 7-O-β-glucoside
Luteolin glucuronide
Luteolin malonylglucoside
Luteolin
Luteolin 7-diglucuronideEclipse XDB C180.03% PA:H2O (A),
solvent A:ACN (1:9 v/v) (B)		injection volume: 20 μL;
flow rate: 0.8 mL/min;
25 °C		DAD, 210, 250, 320, 350 and 370 nmThymus pannonicus[138]
Luteolin 7-O-glucuronide
Abbreviations: Ace, acetone; AcOH, acetic acid; ACN, acetonitrile; AFNH4, ammonium formate; BuOH, butanol; DAD, diode array detector; DAD-ESI-MS, diode array detector combined with electrospray ionization and mass spectrometry; DAD-ESI-MS/MS, diode array detector combined with electrospray ionization and tandem mass spectrometry; DAD-ESI-QTOF-MS, diode array detector combined with electrospray ionization and quadrupole – time of flight mass spectrometry; DAD-MS, diode array detector combined with mass spectrometry; DAD-MS/MS, diode array detector combined with tandem mass spectrometry; DAD-QTOF-MS, diode array detector combined with quadrupole – time of flight mass spectrometry; ESI-IT-MS/MS, electrospray ionization combined with ion trap and tandem mass spectrometry; ESI-MS, electrospray ionization combined with mass spectrometry; ESI-MS/MS, electrospray ionization combined with tandem mass spectrometry; ESI-QTOF-MS, electrospray ionization combined with quadrupole – time of flight mass spectrometry; FA, formic acid; IMS-QTOF-MS, ion-mobility spectrometry combined with quadrupole – time of flight mass spectrometry; MeOH, methanol; MS/MS, tandem mass spectrometry; PA, phosphoric acid; PAD, pulsed amperometric detection; PDA-ESI-MS/MS, pulsed amperometric detection combined with electrospray ionization and tandem mass spectrometry; PDA-ESI-MS, pulsed amperometric detection combined with electrospray ionization and mass spectrometry; PDA-MS, pulsed amperometric detection combined with mass spectrometry; TFA, trifluoroacetic acid; UV/PAD-MS, UV/pulsed amperometric detection combined with mass spectrometry.
Table
Table 5. Liquid chromatography in the analysis of luteolin derivatives.
Table 5. Liquid chromatography in the analysis of luteolin derivatives.
Luteolin DerivativeStationary PhaseMobile PhaseConditionsDetectionAnalyzed SpeciesRef.
LuteolinZorbax SB C18 column with Security-Guard C18 MeOH (A), 0.5% AcOH:H2O (B)flow rate: 1.0 mL/min;
injection volume: 20 μL		MS/MSAbri herba,
A. mollis		[143]
Inertsil ODS-3 0.1% FA:H2O (A), ACN (B)flow rate: 0.5 mL/min;
injection volume: 10 μL		MS/MSCastanea mollissima[144]
RP C18 0.1% FA:H2O (A), 0.1% FA:ACN (B)injection volume: 5 µL;
flow rate: 0.3 mL/min;
40 °C		ESI-MS/MSCentaurea cyanus[145]
Luteolin 7-glucosideEclipse XDB C18 1% FA:H2O (A), MeOH (B)injection volume: 5 mL;
flow rate: 0.6 mL/min;
45 °C		MS/MSPlantago atrata,
P. coronopus,
P. holosteum,
P. lanceolata,
P. reniformis,
P. schwarzenbergiana		[146]
LuteolinZorbax Plus C180.1% FA:H2O (A), 0.1% FA:ACN (B)injection volume: 1µL;
flow rate: 0.4 mL/min		MSMatricaria recutita,
Achillea millefolium,
Thymus vulgaris,
Salvia officinalis		[30]
Eclipse XDB C180.05% FA:H2O (A), MeOH (B)flow rate: 1 mL/minMS/MSVitis vinifera[147]
Luteolin 7-apiosyl-glucosideSymmetry C180.1% FA:H2O (A), 0.1% FA:ACN (B)flow rate: 1.0 mL/min;
25 °C		DAD-ESI-MS;
DAD, 350, 310, 270 nm;
UV, 190-650 nm		Apium graveolens[148]
Luteolin 7-glucoside
Luteolin 7-malonyl-apiosyl-glucoside
Luteolin 7-6’-malonyl-apiosyl-glucoside
Luteolin 7-6’-malonyl-glucoside
Luteolin 3’-glucosideZorbax SB C18 0.1% FA:H2O (A); 0.1% FA:ACN (B)injection volume: 5 μL;
flow rate: 0.3 mL/min;
25 °C		MS/MS; TQMS; ESIPhlomis persica[27]
Luteolin 6-glucoside
Luteolin 6,8-dihexoside
Luteolin 7-rutinosidePh. eliptica
Luteolin 7-rutinosideXTerra MS C18 ACN (A), 0.05% AcOH:H2O (B)injection volume: 20 μL;
flow rate: 1.0 mL/min		PDA-MS; NMRSechium edule[149]
Luteolin 7-glucopyranoside
LuteolinOctadecyl silica gel ODS H2O:MeOH:FA (89:10:1 v/v/ v) (A),
MeOH:H2O:FA (89:10:1 v/v/v) (B)		flow rate: 1 mL/min;
40 °C		MS/MSNepeta cilicica[150]
Luteolin glucuronide
Luteolin glucoside
LuteolinCapcell Park C18 0.5% FA:H2O (A), 0.5% FA:ACN (B)flow rate: 0.5 mL/min;
25 °C		MS/MSHumulus japonicus[151]
Luteolin dihexoside
Luteolin 7-dihexoside
Luteolin 7-rutinoside
Luteolin glucoside
Luteolin 7-acetylglucoside
Luteolin 6-glucosideIntersil ODSACN:H2O:FA (10:89:1 v/v/v) (A),
ACN:H2O:FA (89:10:1 v/v/v) (B)		flow rate: 0.7 mL/min;
40 °C		MS/MSAchillea sivasica[152]
Luteolin glucoside
Luteolin methoxy-2’’-pentosyl-6-hexosideODS2 C8 0.1% FA:H2O (A), ACN (B)flow rate: 0.5 mL/min;
35 °C		DAD-ESI-MS;
280, 370 nm		Geranium molle[68,70,153]
Luteolin 2’’-rhamnosyl-6’’-hexosyl-glucoside
Luteolin 7-glucosyl-8-glucoside
Luteolin 6-glucoside
Luteolin 6-hexosyl-8-pentoside
Luteolin acetylhexosideSpherisorb S3 ODS2 C180.1% FA:H2O (A), ACN (B)flow rate: 0.5 mL/min;
35 °C		DAD-ESI-MS/MSAchillea millefolium[120,154]
Luteolin 6-glucoside
Coleostephus myconis[120]
Luteolin 3-glucuronideRosmarinus officinalis[155]
Luteolin glucuronide
Luteolin hexosyl-pentosideZorbax RP C18 0.1% FA:H2O (A), 0.1% FA:ACN (B)injection volume: 5 μL;
flow rate: 0.4 mL/min;
35 °C		QTOFFicus carica[156]
Luteolin 7-glucoside
Luteolin 7-hexoside
Luteolin 6-hexoside
Luteolin 8-glucoside
Luteolin 6-hexosyl-8-acetyl-hexosideODS2 H2O:ACN:FAinjection volume: 20 μL;
flow rate: 0.8 mL/min		MS/MSOxalis pes-caprae[157]
Luteolin 8-glucosyl-7,3’-dimethoxyl-
2’’-O-glycoside
Luteolin 8-glucosyl-7,3’-dimethoxyl-
6-desoxyhexoside
Luteolin 6-glucosideHydro RP H2O (A), MeOH (B),
5% AcOH:MeOH (C)		flow rate: 1 mL/minMS/MSPassiflora morifolia[158]
Luteolin 8-glucoside
LuteolinLuna C18 0.1% FA:H2O (A), 0.1% FA:ACN (B)flow rate: 0.4 mL/minDAD, 280, 320, 365 nm;
MS; MS/MS		Theobroma cacao[141]
Luteolin 6-glucoside
Luteolin 8-glucoside
Luteolin 7-glucoside
Luteolin 6-glucosieXBridge C18 0.3% FA:H2O (A), MeOH (B)injection volume: 1 μL;
flow rate: 1 mL/min;
40 °C		MS/MS; ESI-MSLophatherum gracile[140]
Luteolin 7-glucoside
LuteolinSymmetry C18 0.1% FA:H2O (A), 0.1% FA:ACN (B)flow rate: 1.0 mL/min;
25 °C		DAD-ESI-MS;
350, 310, 270
and 520 nm		Chrysanthemum morifolium[142]
Luteolin glucuronyl-hexoside
Luteolin 7-pentosyl-hexoside
Luteolin 7-rutinoside
Luteolin 7-glucoside
Luteolin 7-glucuronide
Luteolin glucoside
Luteolin 7-malonyl-6’’-glucoside
Luteolin 7-acetyl-6’’-glucoside
Luteolin 7-dihexoside
LuteolinAcquity BEH C18 0.1% FA:H2O (A), 0.1% FA:ACN (B)flow rate: 0.3 mL/ min;
40 °C		QTOF-MS/MSAgeratum conyoides[159]
Luteolin7-glucuronide
Luteolin hexosideZorbax SB C180.5% FA:H2O (A), ACN (B)injection volume: 5 μL;
flow rate: 0.4 mL/min		MS/MSMatricaria recutita[160]
Luteolin hexosideHypersil gold C181% FA:H2O (A), 0.1% FA:ACN (B)flow rate: 1 mL/minMS/MSCecropia obtusa[161]
Luteolin hexosyl-deoxy-hexose
Luteolin dihexosideSpherisorb S3 ODS-2 C18 0.1% FA:H2O (A),
ACN (B)		flow rate: 0.5 mL/min;
35 °C.		DAD-ESI-MS/MSCotula cinerea[120,162]
Luteolin pentosyl-hexoside
Luteolin 7-glucoside
Luteolin malonyl-hexoside
LuteolinZorbax SB C180.1% FA:AFNH4 (A),
0.1% FA:ACN (B)		injection volume: 1 mL;
flow rate: 0.2 mL/min		ESI-MS/MSOcimum sanctum[163]
Luteolin 8-glucoside
Luteolin 5-glucopyranoside
Abbreviations: AcOH, acetic acid; ACN, acetonitrile; AFNH4, ammonium formate; DAD-ESI-MS, diode array detector combined with electrospray ionization and mass spectrometry; DAD, diode array detector; DAD-ESI-MS/MS, diode array detector combined with electrospray ionization and tandem mass spectrometry; ESI, electrospray ionization; ESI-MS, electrospray ionization combined with mass spectrometry; FA, formic acid; MeOH, methanol; MS/MS, tandem mass spectrometry; PDA-MS, pulsed amperometric detection combined with mass spectrometry; QTOF, quadrupole time-of-flight; TQMS, triple quadrupole mass spectrometer.
Table
Table 6. Gas chromatography in the analysis of luteolin and its derivatives.
Table 6. Gas chromatography in the analysis of luteolin and its derivatives.
Luteolin DerivativeColumnDerivatizationConditionsDetectionAnalyzed SpeciesRef.
LuteolinHP-5-MS1% TMCS:BSTFAcarrier gas: He;
injector temperature: 250 °C
A: (column temperature) 5 min, 170°C;
3 °C/min, 170–255 °C; 1 min, 255 °C; 2 °C/min, 255–310 °C;
flow rate: 0.5 mL/min;
analysis time: 70 min;
B: (column temperature) 5 min, 160°C; 3°C/min, 160–188°C; 1 min, 188 °C; 15 °C/min,
188–241 °C; 1 min, 241 °C; 2 °C/min,
241–282 °C; 5 °C/min, 282–310 °C; 5 min,
310 °C;
flow rate: 1.0 mL/min;
analysis time: 50 min		APCI-TOF-MSFruits of various olives species (Olea L.)[170]
Capillary column Supelco SPBM-5two- and three-phase transfer catalysis (PTC), methyl iodidecarrier gas: He;
injector temperature: 260 °C;
detector temperature: 280 °C;
furnace temperature: 5 min, 50 °C; 5 °C/min, 50–150 °C; 10 °C/min, 150–210 °C;
analysis time: 45 min		MSMentha spicata,
Hypericum perforatum		[179]
non-polar RSL 200 BP0.2 M trimethylaniline hydroxide (TMAH):H2O-free MeOHcarrier gas: N2;
linear speed of the carrier 17.5 cm/s;
0–2 min, 280 °C and 235 °C; 1 °C/min,
280–290 °C;
flow rate: 30 mL/min		FIDdifferent samples form AFRC Institute of Plant Science Research and John Innes Institute, Norwich, U.K.[167]
Py:HMDS:TMCS
BPX5Py:BSTFA:TMCS)
(50:50:1 v/v/v)		carrier gas: He;
injector temperature: 310 °C;
1 min, 100 °C; 30 °C/min, 100–210 °C; 2 °C/min, 210–240 °C; 4 °C/min, 240–270 °C; 5 °C/min, 270–310 °C; 5 min, 310 °C;
flow rate: 1.5 mL/min		QMSPropolis,
Chrysanthemum sp,
Theobroma cacao (bitter chocolate)		[171]
Capillary column Low-bleed CP-Sil 8 CB-MSTMCS (100 μL),
BSTFA (200 μL) HMDS:TMCS:Py
(3:1:9, v/v/v)		carrier gas: He;
2 °C/min, 70–135 °C; 10 min, 135 °C; 4 °C/min, 135–220 °C; 10 min, 220 °C; 3.5 °C/min, 220–270 °C; 20 min, 270 °C;
injector temperature: 280 °C;
detector temperature: 290 °C;
flow rate: 1.9 mL/min		MSTeucrium polium[169]
Quartz capillary columnPy:BSTFA
(1:1 v/v)		carrier gas: He;injector temperature 220 °C;
detector temperature: 270 °C;
2.3 °C/min 200–270 °C; 30 min, 270 °C		MSAspalathus linearis[172]
Luteolin 7,3’,4’-trimethylCapillary column Permabond OV-1---carrier gas: N2, He;
injector temperature: 300 °C;
column temperature: 270 °C (isothermal);
flow rate: 1.3 mL/min		FIDArnica alpina[168]
Capillary column OV-1---MS
Abbreviations: Py, pyridine, BSTFA, N,O-bis(trimethylsilyl)trifluoroacetamide; TMS, trimethylsily; HMDS, hexamethyldisilazane; TMCS, trimethylchlorosilane; APCI-TOF-MS, atmospheric pressure chemical ionization combined with quadrupole – time of flight mass spectrometry; FID, flame ionization detector; QMS, quadrupole mass spectrometry.
Table
Table 7. Counter-current chromatography, as a preparative technique in the separation of luteolin derivatives.
Table 7. Counter-current chromatography, as a preparative technique in the separation of luteolin derivatives.
Luteolin DerivativeSolvent SystemConditionsDetectionAnalyzed SpeciesRef.
Luteolin 6-glucosideEtOAc:BuOH:H2O
(2:1:3 v/v/v)		rotation speed: 800 rpm;
flow rate (lower phase): 2.4 mL/min		UV-VIS, 254 nm;
NMR; MS		Patrinia villosa[173]
Luteolin 7-glucosideEtOAc:EtOH:AcOH:H2O
(4:1:0.25:5 v/v/v/v)		rotation speed: 800 rpm;
flow rate (lower phase): 1.5 mL/min		UV, 254 nm;
NMR; MS		Paeonia suffruticosa[177]
Luteolin 6,8-dihexosideHx:EtOH:H2O
(4:3:1 v/v/v)		rotation speed: 850 rpm;
flow rate (lower phase): 2 mL/min		TLC; HPLC-UV-HRMSLippia origanoides[178]
Luteolin 8-glucoside
Luteolin 6-glucoside
Luteolin 7-glucoside
Abbreviations: AcOH, acetic acid; BuOH, butanol; EtOAc, ethyl acetate; EtOH, ethanol; HRMS, high resolution mass spectrometry; Hx, hexane, rpm, revolutions per minute.

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Juszczak, A.M.; Zovko-Končić, M.; Tomczyk, M. Recent Trends in the Application of Chromatographic Techniques in the Analysis of Luteolin and Its Derivatives. Biomolecules 2019, 9, 731. https://doi.org/10.3390/biom9110731

AMA Style

Juszczak AM, Zovko-Končić M, Tomczyk M. Recent Trends in the Application of Chromatographic Techniques in the Analysis of Luteolin and Its Derivatives. Biomolecules. 2019; 9(11):731. https://doi.org/10.3390/biom9110731

Chicago/Turabian Style

Juszczak, Aleksandra Maria, Marijana Zovko-Končić, and Michał Tomczyk. 2019. "Recent Trends in the Application of Chromatographic Techniques in the Analysis of Luteolin and Its Derivatives" Biomolecules 9, no. 11: 731. https://doi.org/10.3390/biom9110731

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