Fluoroquinolones have been used as antibiotics for more than four decades [1]. This is one of the most successful marketing projects in the history of antibiotic therapy. There is no generally accepted scientific classification of fluoroquinolones. Historically, they are divided by generation and by the number of fluorine atoms in the molecules (monofluoroquinolones, difluoroquinolones, and trifluoroquinolones). There are four generations of drugs in this series, but the third and fourth ones have not significant differences in antibacterial terms. Of greatest clinical importance is their antimicrobial activity against gram-negative flora, including strains resistant to penicillins, cephalosporins, and aminoglycosides, which made it possible to use this group for the treatment of severe nosocomial (hospital) infections. Fluoroquinolones of the third and fourth generations (sparfloxacin, clinafloxacin, gatifloxacin, etc.) are also active against gram-positive cocci [2]. According to another classification, fluoroquinolones are divided into three groups according to the preferential inhibition of topoisomerase IV, DNA gyrase, or both enzymes [1].

Recent studies have revealed new properties of fluoroquinolones, in particular, antiviral and antitumor properties including anticancer effects [1, 3]. At the same time, the unsuccessful marketing policy of pharmaceutical companies provokes a long-term and dose-dependent mechanism for the development of microbial resistance to fluoroquinolones, which reduces their effectiveness [4, 5]. The widespread and not always justified use of antibiotics in the food industry, agriculture, veterinary medicine, and medicine; the problems of the pharmacokinetics and pharmacodynamics of fluoroquinolones in humans and animals and birds grown on farms; and the presence in environmental objects serve as the basis for continuous improvement of methods for their determination in these areas. Several reviews on the determination of fluoroquinolones have been published, which indicated that high performance liquid chromatography with photometric, fluorimetric, or mass-selective detection are the most frequently used methods for this purpose [6–8]. These methods require the involvement of expensive equipment and qualified specialists.

Various versions of fluorescence analysis are widely used for the determination of fluoroquinolones along with chromatography. One of the attractive fundamental features of this method is the existence of several approaches to increasing the quantum yield of fluorophores and improving the sensitivity and selectivity of the determination of analytes, including fluoroquinolones. These approaches are based on the use of time-resolved fluorescence, synchronous spectrofluorometry, and various types of sensitized fluorescence based on excited state resonance energy transfer (RET) [9–14]. As a rule, the sensitized fluorescence of fluoroquinolones is based on the formation of antibiotic chelates with lanthanide ions, and it is combined with an analytical reaction on/at the surfaces of liquid and solid nanoobjects [11, 15, 16]. The simplicity of analytical procedures, the availability of instrumentation, and the high sensitivity of the fluorimetric method of analysis are the basis for the continued interest in its use for the determination of antibiotics.

Liquid nanoobjects, such as micelles or microemulsions based on surfactants, act as nanoreactors in which an antibiotic or its chelate with a metal ion is solubilized. Solubilization in the bulk of a nanophase improves the solubility of fluorophores and their complexes with metals, changes their hydration and hydrophobic and complexing properties, increases the structure rigidity of the fluorescent center, improves the efficiency of excitation energy transfer, and, as a result, increases the sensitivity of the determination of antibiotics [15, 16].

The influence on the fluorescence of solid nanoobjects, primarily, various nanoparticles (NPs) of noble metals and quantum dots (QDs), is associated with the effects of sorption and local surface plasmon resonance (LSPR), as well as energy transfer as a result of overlapping absorption (fluorescence) spectra of nanoparticles and lanthanide chelates with antibiotics [11, 16]. Among metal NPs, silver and gold nanoparticles (Ag NPs and Au NPs, respectively) are most commonly used because their plasmon resonance bands are located in the visible region of the spectrum, and they overlap with the absorption and emission bands of fluoroquinolones themselves and their complexes with lanthanides. High molar light absorption coefficients, unique surface sorption properties, and easily varied optical characteristics contribute to the wide use of solid nanoobjects in chemical analysis. It can be assumed that the combined use of surfactants and nanoparticles in an analytical system can open up new possibilities for increasing the sensitivity and selectivity of the fluorimetric determination of antibiotics, and it is of interest for analytical practice in the determination of biologically active substances.

The purpose of this work was to analyze publications over the past decade devoted to methods and new approaches to increasing the sensitivity and selectivity of the fluorescence determination of fluoroquinolones using liquid and solid nanoobjects, mainly, with energy transfer in an excited state.

ENERGY TRANSFER EFFECTS IN THE NANOOBJECT–FLUOROQUINOLONE SYSTEMS

Nonradiative electronic excitation energy transfer is a fundamental physical phenomenon, which plays an important role in naturally occurring processes, especially, in photosynthesis and in optoelectronics, biochemistry, coordination chemistry of transition metals and lanthanides, and luminescence analysis including the determination of antibiotics [11]. RET is an optical process in which the excess energy of an excited molecule, usually referred to as a donor, is transferred to an acceptor molecule (Fig. 1). Energy transfer implies the presence of a donor (D), which absorbs light, and an acceptor (A), which receives the absorbed and converted energy of the donor for the subsequent emission. The energy transfer process can be schematically presented in the simple form D* + A → D + A*, where an asterisk marks a molecule in an excited state. The version of emission resulting from singlet–singlet transitions during energy transfer is called sensitized fluorescence or sensitized phosphorescence in the case of triplet–triplet or triplet–singlet transitions.

Fig. 1.
figure 1

Schematic diagram of the processes of (a) conventional fluorescence with emission of a light quantum of lower energy, (b) upconversion with emission of a quantum of higher energy, and (c) sensitized fluorescence of a europium chelate with a ligand.

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It was demonstrated that light absorption and the subsequent electron energy transfer in an excited state, accompanied by a bathochromic shift of the emission spectrum of the acceptor with respect to the donor, can occur in the following cases [11]:

— in dynamic collision of ions and molecules D and A in solution;

— inside a molecule having two reaction centers (D and A) with different conditions of light absorption and emission;

— inside a metal chelate formed, for example, by a lanthanide ion (A) and an antibiotic (D);

— between dissolved molecules (ions) and nanoparticles.

Furthermore, on the contrary, in the case of two-photon light absorption, energy transfer can occur with the acceptor emission of light with a higher energy (increased frequency) than that absorbed by the donor, the so-called upconversion process [17] (Fig. 1).

For energy transfer, the donor and the acceptor should be at a distance of several nanometers; therefore, energy transfer in a homogeneous solution is pos-sible only at sufficiently high concentrations (10–3–10–2 M) of both components. This situation is of no interest for chemical analysis. The use of liquid and solid nanoobjects in luminescence analysis has radically changed the situation. The use of nanoobjects of both types led to local concentration and convergence of the donor and the acceptor of excitation energy in/on the nanoobject, an increase in the transfer probability, and a decrease in the detection limit of the analyte by several orders of magnitude.

Both liquid, mainly micellar, nanosystems and solid nanoparticles of different nature are used to determine fluoroquinolones [11]. The fundamental difference in the resonance energy transfer (RET) between these two types of nanoobjects should be emphasized. Thus, micelles, microemulsions, cyclodextrins, and other nanosystems in solution play the role of nanoreactors concentrating and bringing D and A molecules together in a confined space of the nanoobject due to the effect of their joint solubilization. Therefore, micelles themselves do not participate in energy transfer. Their other role is to change the micropolarity, microacidity, and microviscosity of the microenvironment of the donor–acceptor (D–A) pair, isolate it from the influence of quenchers, hydrate water molecules, and implement the inductive-resonance or exchange-resonance type of fluorescent (Förster) RET (FRET).

The condition for nonradiative energy transfer in FRET is the partial overlap of the emission spectrum of the donor with the absorption spectrum of the acceptor, which are involved in the dipole–dipole interaction or adduct formation. In this case, the distance between the donor and the acceptor should usually be no greater than 10 nm [11], and this condition easily occurs in surfactant micelles, whose size is much smaller than 10 nm. The condition for the overlapping of the spectra of the donor and acceptor is that they have partially identical or close sets of energy levels. This fact is a potential opportunity to improve the selectivity of determinations by a luminescence method.

Another type of energy transfer in micelles is lanthanide resonance energy transfer (LRET), which by its nature is an exchange resonance intramolecular transfer of excitation energy from a donor ligand molecule, such as an antibiotic, to a complexing lanthanide ion [11]. As a rule, terbium is the lanthanide ion in the determination of fluoroquinolones, and it is europium for tetracyclines; this is due to the mutual arrangement of the triplet levels of these antibiotics and the radiative level of the lanthanide (see Fig. 1c). In both cases, the donor has higher radiation energy, and the acceptor has lower energy; that is, the emission spectrum of the donor is hypsochromic with respect to the absorption spectrum of the acceptor [12, 13]. The energy loss is caused by the rapid vibrational relaxation of the donor molecule in an excited state, and it is expressed in terms of the Stokes shift, which is hundreds of nanometers for LRET. In addition to an increase in the fluorescence intensity due to the sensitization effect, fluorescence quenching by an analyte caused by energy transfer is also used in analysis [18].

When antibiotics interact with solid nanoparticles, there are a much larger number of energy transfer scenarios because it becomes possible for the nanoparticles themselves, which can be both donors and acceptors of excitation energy, to participate in the energy transfer (Fig. 2). It should be noted that there is no established terminology for the designation of energy transfer involving nanoparticles. Some authors used the term surface-enhanced fluorescence (SEF) [19–23], others used the term metal-enhanced fluorescence (MEF) [9, 24–31], and still others used the terms plasmon-enhanced fluorescence (PEF) [32–34], plasmon-coupled fluorescence (PCF) [35, 36], plasmon-controlled fluorescence [37], metal-coupled fluorescence (MCF) [38] or localized surface plasmon resonance (LSPR) spectroscopy, and plasmon-induced resonance energy transfer (PIRET) [39].

Fig. 2.
figure 2

Possible versions of energy transfer involving liquid and solid nanoobjects.

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In fact, when forming a term, the authors took into account different factors that cause a change in the fluorescence signal intensity for the same D–A system. Some noted the participation of a metal nanoparticle in energy transfer (MEF and MCF), others noted the effect of an electromagnetic field created by the nanoparticle surface (SEF), and still others noted the participation of plasmonic nanoparticle’s electrons (PEF and PCF). In all of the above types other than PIRET, the D–A pair consisted of a metal nanoparticle and an organic fluorophore or a metal–ligand chelate. The dipole–dipole interaction in FRET leads to incoherent energy transfer from the donor to the acceptor, and it is characterized by a bathochromic shift of the maximum of the sensitized fluorescence spectrum.

In the case of PIRET, the excitation energy transfer occurs between metal nanoparticles and a semiconductor QD [39]. A metal nanoparticle absorbs light and, as a result of the dipole–dipole interaction, transfers the energy of plasmons from the metal to the semiconductor, in which electron–hole pairs are generated below and near the edge of the semiconductor band. Plasmons have a large dipole moment, and the collective oscillations of their electrons are coherent; this creates the possibility of a strong hypsochromic shift of the fluorescence spectrum. PIRET differs from classical FRET in the absence of a Stokes shift, nonlocal absorption effects, and strong dependence on the plasmon skew rate and dipole moment. PIRET can nonradiatively transfer excitation energy through the insulating layer, which prevents interfacial recombination charge losses and plasmon dephasing due to hot electron transfer [39].

The listed types of electron excitation energy transfer, its mechanisms, and features in systems involving nanoparticles were considered in a number of reviews [29, 31, 40–42]. It has been shown that many nanoparticles of different nature, such as silver, gold, and silicon nanoparticles, semiconductor QDs, and carbon and magnetic nanoparticles (MNPs) can participate in energy transfer.

In the case of localized surface plasmons, light interacts with nanoparticles whose size is much smaller than the wavelength of incident light. This leads to the appearance of a plasmon (a cloud of excited electrons), which locally oscillates around the nanoparticle with a frequency known as LSPR [43]. The efficiency and result of energy transfer depend on the distance in the donor–acceptor pair [44, 45]. If it is smaller than 5 nm and the fluorescence spectrum of the fluorophore overlaps with the plasmon spectrum of the nanoparticle, fluorescence quenching is usually observed. If this distance exceeds 5 nm, the effect of FRET quickly becomes negligible because its efficiency drops as 1/r6 (where r is the distance between the plasmon and the fluorophore). In this case, energy transfer is determined by the Purcell effect, which decreases as a function of 1/r3. This effect is expressed in an increase in the rate of spontaneous emission of a fluorescent molecule under the influence of a strong local field, so-called hot spots generated by nearby plasmon nanostructures. The Purcell effect can be maximal if the LSPR band overlaps with the fluorescence emission band. At a distance between an organic molecule and a nanoparticle from 5 to 90 nm, both amplification and quenching of fluorophore radiation are possible [29]. If this distance exceeds 90 nm, there is no transfer, and the fluorescence intensity of the fluorophore does almost not change.

The nature of changes in the fluorescence of an organic molecule depends on its optical characteristics. In the case of overlapping the spectra of fluorophore absorption and LSPR, a slight increase in the emission of the fluorophore, an increase in the quantum yield as a result of MEF or SEF, and a change in the lifetime of the fluorophore are possible [44, 46–49].

The degree of influence of nanoparticles on the optical properties of a fluorophore is also related to the size and shape of nanoparticles, the orientation of dipole moments, the quantum yield of the fluorophore, and the nature of the solvent. The effects of enhancing the fluorescence of an organic molecule near the structure of metal nanoparticles have been used in the development of highly sensitive chemical and biochemical sensor systems [9, 19, 23, 25, 29, 50–57].

There are several important factors that determine the increase in the fluorescence intensity of a fluorophore in the presence of noble metal nanoparticles [29]. One of the main factors is the effect of amplification of the local electromagnetic field generated near metal nanoparticles [58, 59]. Nanoparticles interact with incident light and produce concentrated electric fields with localized charge density fluctuations: the resulting LSPR changes the optical properties of fluorophores located near the surface of the particle. As a result, the fluorescence intensity of organic molecules, which effectively interact with the electromagnetic field of free metal electrons, increases significantly. Under conditions of resonant excitation, the shape and size of nanoparticles play an important role in the formation of the fluorescence of organic molecules because the sharp corners and edges of metal nanostructures maximize the electric field [33, 60]. In this case, the metal nanostructures act as an antenna for a localized electric field and effectively affect the fluorophore near the surface of the nanoparticles.

Another factor that determines the increase in the fluorescence intensity of a molecule is the effect of plasmonic action of metal nanoparticles associated with nonradiative SPR energy transfer to the fluorophore [61]. The mechanism of resonance excitation energy transfer (FRET) takes place if the nanoparticle and the fluorophore are at an optimal distance [46]. The efficiency of the process depends not only on the strength of an electric field but also on the degree of overlap between the LSPR spectrum of nanoparticles and the absorption spectrum of the fluorophore [47, 59]. Experimental and theoretical studies have shown that the rates of excitation and emission of a fluorophore increase when the absorption spectra of nanoparticles overlap with the absorption spectra of the fluorophore [27, 48].

The next important factor in increasing the efficiency of a radiative process is associated with an increase in the rates of radiative and nonradiative processes and the number of excitation‒emission cycles [49, 59, 62] accompanied by a decrease in the fluorescence lifetime and an increase in the quantum yield and fluorophore fluorescence intensity.

A distinction is made between resonant and nonresonant excitation of a fluorophore in the presence of nanoparticles. As a result of the simultaneous absorption of excitation energy by a nanoparticle and an organic molecule, the fluorophore is resonantly photoexcited and its fluorescence is enhanced if the distance between the fluorophore and the metal nanoparticle is in a range of 5–90 nm. Under nonresonant excitation, the energy of an organic molecule is transferred to a metal nanoparticle, which can subsequently fluoresce [63], while the fluorescence intensity of the fluorophore decreases as a result of the transfer of excitation energy to the metal nanoparticle.

DETERMINATION OF FLUOROQUINOLONES WITH THE PARTICIPATION OF NANOPARTICLES

The main effect used in the fluorescence determination of fluoroquinolones is energy transfer in the nanoparticle–fluorophore system, that is, sensitized fluorescence [11, 16]. Table 1 summarizes publications on methods used for the determination of fluoroquinolones with the participation of NPs. It follows from Table 1 that fluorescence methods have been proposed for the determination of fluoroquinolones with the use of silver [9, 64–66] and gold [67] nanoparticles and quantum dots based on semiconductor materials, such as ZnS [68, 69], CdTe [70, 71], MoS2 [72], etc. [73]. In addition to semiconductor QDs, carbon QDs [54, 74, 75] and other carbon nanomaterials, such as graphene [75, 76] or carbon nanotubes (CNTs) together with semiconductor QDs [71], are used to determine fluoroquinolones. In some cases, magnetic nanoparticles of magnetite together with other NPs [68, 76, 77] and MNPs of a different composition in combination with chemiluminescence determination [78] were used to separate fluoroquinolones adsorbed by nanoparticles.

Table 1.   Fluorimetric determination of fluoroquinolones with the use of nanoobjects
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An interesting approach to the determination of fluoroquinolones based on the upconversion phenomenon, that is, excitation of one component of the system in the long-wavelength region and emission of another component in the short-wavelength part of the spectrum, was proposed [77, 79]. These NPs were sometimes coated with polymers with molecular imprints of the fluoroquinolones to be determined. The list of nanoparticles for the fluorescence determination of fluoroquinolones includes silicon [80] and silicon dioxide [81] nanoparticles, a combination of AgBr NPs and Ti3C2 MXene [82], and the use of DNA to increase the fluorescence signal [83].

A large number of works were devoted to the determination of fluoroquinolones, the complexes of which were incorporated into various nanosized polymeric nanoparticles, for example, polystyrene [84], methacrylic acid [85], methacrylic acid and 2-hydroxyethyl methacrylate [86], and terbium-coordinating polymer nanosheets [87], which contacted with metal nanoparticles or QDs. A new direction in the determination of fluoroquinolones is the use of photonic crystals [88].

An analysis of data given in Table 1 led to a conclusion that the proposed different types of nanoparticles make it possible to determine fluoroquinolones in concentration ranges that differ by several orders of magnitude. Determinations at the levels of attomoles with Ag NPs [65], nanomoles with quantum dots [69, 70, 73, 76, 77, 81], and micromoles [80, 86–88] have been described. However, it is difficult to draw final conclusions about which nanoobjects are better. Thus, on the one hand, the determination sensitivity in fluorimetry depends on the power of an excitation source used in the instrument; on the other hand, the selectivity of determination of an antibiotic should also be taken into account.

Let us consider the results obtained in more detail. The metal-enhanced fluorescence of fluoroquinolones was observed for the first time in aqueous solutions in the presence of silver nanoparticles, and it was applied to the determination of this group of antibiotics [9, 64]. Yin et al. [9] and Wang et al. [64] proposed to synthesize silver nanoparticles in an aqueous medium using β-cyclodextrin as a stabilizer. It was found that the fluorescence of enrofloxacin, lomefloxacin, and norfloxacin first increased with the concentration of nanoparticles in the solution and then decreased. The fluorescence spectra of the fluoroquinolones significantly overlapped with the LSPR spectrum of silver nanoparticles (400 nm) to facilitate an increase in the fluorescence intensity of all three antibiotics, which was used to determine the fluoroquinolones in drugs. Noble metal nanoparticles, along with the intrinsic fluorescence of fluoroquinolones, also enhanced the sensitized fluorescence of antibiotic complexes predominantly with terbium ions [8, 56, 89].

The idea of creating a fluorescent biosensor for the determination of ofloxacin in water and milk samples was implemented using an unlabeled ofloxacin-specific aptamer, Au NPs, and Rhodamine B [67]. The Au NPs were coated with the ofloxacin aptamer, which quenched the emission of the Rhodamine B fluorophore in the sensitive layer of the biosensor. Ofloxacin interacted with the aptamer to cause its removal from the surface of Au NPs, the release of molecules of Rhodamine B, and an increase in its fluorescence.

Roy and Roy [66] proposed an alternative use of fluoroquinolone, in which levofloxacin acted as a modifier of the surface of silver nanoparticles in the analytical system. The developed chemosensor made it possible to determine Hg2+ and Fe3+ ions in solutions at a level of 10–9–10–8 M.

Sensors for fluoroquinolones based on the sensitized fluorescence of europium and terbium ions have been proposed [84, 87]. The combination of polymers with a molecular imprint (MIP) of ciprofloxacin and europium(III) complexes with tris(dibenzoylmethane)(1,10-phenanthroline) embedded in polystyrene microparticles was used to determine this fluoroquinolone in fish samples [84]. Ciprofloxacin was captured by the MIP to quench the sensitized fluorescence of the mixed-ligand europium chelate, which provided its specific detection and highly sensitive determination. Xu et al. [87] proposed nanomaterials from coordination polymers containing adenosine monophosphate and Tb3+ ions as a sensor platform for the screening detection of fluoroquinolone residues in milk.

Sari et al. [85] proposed an original nanosensor containing nanoparticles of gold and a polymer with a molecular imprint, which was synthesized by mini emulsion polymerization of methacrylic acid, for the detection of ciprofloxacin in water using LSPR. Another approach to the use of methacrylic acid polymer nanoparticles with molecular imprints of 160 nm in size for the determination of ciprofloxacin was based on their covalent grafting onto a cantilever [86]. The sensor made it possible to determine ciprofloxacin in an aqueous solution in a range of 1.5–151 μM with a detection limit of 0.8 μmol.

The antenna effect was used to determine ciprofloxacin using fluorescent silicon nanoparticles in the presence of Eu3+ ions. The introduction of ciprofloxacin markedly increased the intensity of the sensitized fluorescence of the Eu3+ ion at 590 and 619 nm [80].

There are several options for using quantum dots for the luminescence determination of fluoroquinolones based on polymers with a molecular imprint [83, 90, 91] and with the use of aptamers [54, 82, 90] or immunosensors [73, 90]. Quantum dots can act as fluorescent labels, energy donors, matrix carriers, and dye-sensitive targets in the recognition units of sensory systems [90]. Quantum dots modified with molecularly imprinted polymers make it possible to achieve not only low detection limits but also unique selectivity in the determination of antibiotics. The combination of aptamers with quantum dots promotes high binding affinity, ease of modification, and long-term stability of the analytical system. The combination of nanoparticles and a polymer with a MIP in the technique significantly expands the possibilities of chemical determination, recognition of antibiotics from the series of fluoroquinolones, and monitoring in complex objects of analysis [90].

Sri et al. [72] proposed QDs of a new type based on molybdenum disulfide for the fluorimetric determination of tetracycline and levofloxacin. In the presence of tetracycline, dynamic quenching of the luminescence of these QDs was observed. Additives to the analyzed solution of levofloxacin led to the formation of a new more stable complex with a photoinduced electron transfer process accompanied by an increase in fluorescence intensity. The proposed sensor was used for the analysis of water, wastewater, and milk samples.

Zinc sulfide quantum dots doped with Tb3+ ions and polyethylene glycol increased the fluorescence intensity in the presence of norfloxacin [69]. The resulting complex with energy transfer to nanoparticles was characterized by high fluorescence intensity. The sorption activity of the surface of QD nanoparticles contributed to the concentration of the analyte and decreased the detection limit to tenths of a nanomole in the determination of norfloxacin in urine and pharmaceutical preparations.

Carbon nanomaterials for the determination of fluoroquinolones were used in the forms of CNTs [71], graphene, and graphene oxide [54, 74]. Most often, they were combined with semiconductor QDs, for example, CdTe [71], Gd3+ salt additives [54], molecularly imprinted polymers for the fluoroquinolone to be determined [74], or magnetite and silicon dioxide nanoparticles [75]. The incorporation of hydroxyapatite and graphene QDs into a highly selective polymer made it possible to obtain a nanoprobe for the determination of norfloxacin [92]. Hydroxyapatite promoted the adsorption of norfloxacin on the sensitive layer, graphene QDs increased the analytical signal sensitivity, and the polymer with a molecular imprint ensured the selectivity of antibiotic determination in chicken meat and milk [92]. A nanocomposite optosensor probe based on porous carbon and graphene QDs embedded in a selective polymer was proposed to detect traces of ofloxacin in milk [74].

Immunoassay technology has been used to detect toxicants in various samples for more than three decades. The limitations of this method are associated with the generation of antibodies against low-molecular-weight targets, which do not cause an immune response, and the low stability of antibodies under environmental conditions. As an alternative, the use of aptamers as more stable analytical tools for the detection of a wide range of analytes, including antibiotics, was proposed. Due to their high specificity in target recognition, aptamers are considered reliable elements of molecular recognition. Reviews [54, 93–95] discussed the latest achievements in the field of aptasensors for the detection of various pollutants, including antibiotics.

An aptasensor for the determination of enrofloxacin in powdered milk samples was based on the measurement of fluorescence resulting from resonance excitation energy transfer from NaYF4:Yb/Er/Gd@NaYF4 nanoparticles to graphene oxide [54]. The high efficiency of analyte adsorption in the sensitive layer was ensured by the inclusion of nanoparticles in a polymer, the noncovalent interaction of the analyte, and the formation of hydrogen bonds. Doping of the surface of nanoparticles with Gd3+ ions promoted a shift of the fluorescence signal to the IR region and leveled the matrix autofluorescence. This technique made it possible to lower the detection limit by a factor of 13, as compared to that of a commercial enzyme kit for the enzyme immunoassay for enrofloxacin. Another aptamer for the determination of enrofloxacin in the analysis of fish and shrimp reacted on conformational changes in the sensitive layer that occurred in the presence of the analyte and contributed to an increase in the fluorescence intensity [79]. Nontoxic and efficient near-infrared phosphors were used to determine enrofloxacin with a wavelength-tunable aptasensor [82].

Magnetic solid-phase extraction (MSPE) with the use of sorbents controlled by an external magnetic field makes it possible to avoid the steps of solution centrifugation and filtration and opens up new opportunities for the rapid determination of fluoroquinolones [10]. The MSPE of fluoroquinolones with the subsequent luminescence determination of total antibiotics was described [68, 76, 77]. For the fluorimetric determination of sparfloxacin and orbifloxacin, it was proposed to use different nanoparticles for the following two purposes: the separation of an analyte adsorbed on magnetite nanoparticles by the action of a permanent magnet and its subsequent fluorimetric determination in milk and natural water using boron-doped carbon QDs [76]. The nanohybrid magnetic fluorescent probe for the determination of levofloxacin consisted of porous graphene, magnetite nanoparticles, and graphene QDs embedded in a selective polymer with a molecular imprint. The high selectivity provided by the use of MIP made it possible to determine levofloxacin in the presence of ciprofloxacin, lomefloxacin, marbofloxacin, and sarafloxacin [75]. An automated chemiluminescence method for the screening of total fluoroquinolones in milk samples using micro-solid-phase extraction in a flow system with Zr–Fe–C magnetic nanoparticles was described by Vakh et al. [78].

Tang et al. [77] described the layer-by-layer assembly of a fluorescent probe based on a molecularly imprinted polymer, upconversion NaYF4 nanoparticles, and Fe3O4 nanoparticles. The sorption properties of the polymer were studied using enrofloxacin as an example. A wide range of spectral and magnetic properties of the sensor and the possibility of molecular recognition and determination of a number of fluoroquinolone derivatives (enrofloxacin, fleroxacin, levofloxacin, ciprofloxacin, and enoxacin) made it possible to use this sensor in the analysis of complex biological materials, such as fish tissues [77].

DETERMINATION OF FLUOROQUINOLONES IN THE PRESENCE OF SURFACTANT MICELLES

The influence of surfactant micelles on the electronic excitation energy transfer and sensitized fluorescence of lanthanide complexes with fluoroquinolones was most actively studied in the late 1990s and the first decade of the 2000s [96]. In the last decade, the number of studies devoted to the use of organized media based on surfactant micelles for the determination of fluoroquinolones has decreased. Table 2 summarizes the main publications in which procedures for the determination of some fluoroquinolones in samples with the use of surfactants were considered. From Table 2, it follows that the micelles of anionic surfactants (ASs), mainly sodium dodecyl sulfate or sodium dodecylbenzenesulfonate, were used in most cases. The specific influence of the ASs can be associated with the ability of negatively charged micelles to concentrate lanthanide cations on their surface due to electrostatic interactions, while the solubilization of fluoroquinolone ligands in micelles is mainly due to the hydrophobic interaction of the hydrocarbon skeleton of their molecules with the hydrocarbon radicals of AS ions [11, 13, 108]. A significant increase in the fluorescence intensity of most fluoroquinolones is achieved by the formation of Tb3+, rarely Eu3+, chelates due to the peculiarities of the mutual arrangement of the triplet level of the fluoroquinolone and the emitting level of the lanthanide ion [11, 13, 111].

Table 2.   Fluorimetric determination of fluoroquinolones in the presence of surfactant micelles
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In the presence of ASs, in addition to an increase in the sensitized fluorescence of binary chelates of lanthanides, their complexation plateau also expanded due to changes in the protolytic properties of flavonoids [11, 15]. An increase in the fluorescence intensity in micellar media can be caused by several reasons: the solubilization and partial dehydration of coordinatively unsaturated complexes in a less polar micelle microenvironment and also the removal of water molecules from the coordination sphere of the lanthanide ion as a result of the possible entry of the surfactant anion as an independent ligand into the coordination sphere of the lanthanide.

A generalization of the available results makes it possible to conclude that an additional increase in the intensity of the sensitized fluorescence of europium and terbium with fluoroquinolones is determined by three factors: the use of a second ligand; the use of a second lanthanide, more often, Gd3+; and carrying out the reaction in a micellar solution or introducing globular biopolymers like albumin, which form a more rigid structure of the fluorescent center, into the solution. As a result, the combined use of these factors makes it possible to increase the intensity of sensitized fluorescence by almost two orders of magnitude and to decrease the detection limit of fluoroquinolones by two or three orders of magnitude.

In the case of high hydrophobicity of the second ligand and the entire mixed-ligand complex, it was proposed to use microemulsions with a higher solubilizing ability and solubilization capacity instead of a micellar surfactant solution [11, 13, 109]. The action of the second ligand may also result in chelate fluorescence quenching, which is of analytical significance. The reason is the formation of a stronger and less fluorescent complex; that is, quenching proceeds by a static mechanism.

The simultaneous use of a second ligand and solubilization in surfactant micelles additionally decreased the number of water molecules coordinated by a lanthanide, which are responsible for nonradiative deactivation of the energy of an excited state of the metal ion. These characteristics are also influenced by the lipophilicity, ligand basicity, acidity of the medium, the lifetime of excited states, and the ratio between the rates of nonradiative and radiative processes in aqueous and micellar media [11, 12].

It was shown that, when second ligands containing chromophore groups were used, an increase in the fluorescence intensity was associated not only with the substitution for residual water molecules but also with additional ligand–ligand or ligand–metal intramolecular excitation energy transfer, that is, an enhancement of the antenna effect, which was also characteristic of lanthanide chelates with tetracyclines in nonionic surfactant micelles [13, 111]. The joint action of the second lanthanide ion and the second ligand can result in the formation of hydrophobic heteronanoparticles, in which the intermolecular and intramolecular mechanisms of excitation energy transfer from the complexes of the second lanthanide to the europium complex occur [112].

A differentiating effect of the nature of organized media on the intensity of intrinsic and sensitized fluorescence of binary and mixed-ligand chelates of europium and terbium with various fluoroquinolones due to their solubilization by surfactant micelles was revealed. For example, the micelles of anionic surfactants increased the fluorescence of terbium chelates with phenanthroline and ligands of the same class of fluoroquinolones—norfloxacin and flumequin, and the micelles of nonionic surfactants quenched it, while cationic surfactants acted differently [12, 110]. Anionic surfactant micelles quenched the fluorescence of Eu3+–DC–Phen and Tb3+–OA–Phen chelates, while cationic surfactant micelles, on the contrary, increased it. Micelles of nonionic surfactants significantly increased the fluorescence of Eu3+–DC–Phen and did not change the fluorescence of europium chelates with EF, NA, and OA [110]. The effect of micelles on a terbium chelate with nalidixic acid and Phen, whose fluorescence was quenched by micelles of only cationic surfactants, in contrast to the chelate of another quinolone, oxolinic acid, can be explained by solubilization features [110]. It was shown that the enhancement of fluorescence was associated with the solubilization of chelates into micelles, while quenching was associated with their destruction due to the competitive interaction of micelle ions with metal ions or ligands or the absence of chelate solubilization in a micelle. Thus, the efficiency of energy transfer can be increased or decreased by varying the concentration and nature of surfactants and synergistic and antagonistic effects in the lanthanide–fluoroquinolone–second ligand–surfactant system can be regulated.

Smirnova et al. [113] proposed a new approach to the fluorimetric determination of levofloxacin and ofloxacin; this approach consisted in the simultaneous use of silver nanoparticles and SDS micelles for energy transfer. In this system, the Y3+–Lef–SDS and Y3+–OP–SDS chelates were localized on silver nanoparticles coated with an anionic surfactant layer and had a hydrophobic environment. Energy transfer included not only chelate components but also silver nanoparticles. It was shown that the surface modification of silver nanoparticles with anionic surfactant micelles made it possible to expand the ranges of determined concentrations of ofloxacin and levofloxacin to three orders of magnitude and to lower the detection limit by two orders of magnitude. Table 2 illustrates the practical applications of energy transfer in surfactant micelles for the determination of fluoroquinolones in specific samples.

CONCLUSIONS

An analysis of published data revealed a steady trend towards the use of nanoobjects for the determination of fluoroquinolones by the method of sensitized fluorescence based on the transfer of electronic excitation energy upon the formation of chelates with terbium and europium ions. Sensitized fluorescence was also used in sensors, DNA probes, flow cytometry, and homogeneous and heterogeneous immunoassays and also in combination with a preliminary chromatographic separation or the isolation of fluoroquinolones. Previously, the problem of increasing the determination sensitivity of ligand analytes, including fluoroquinolones, was solved by going from homoligand chelates to mixed-ligand chelates (antenna effect), using biomacromolecules, or varying the reaction medium. In the 21st century, a new trend has emerged based on the use of liquid micellar nanosystems (organized media) and, more recently, the nanoparticles (mainly quantum dots) of noble metals, semiconductors, and carbon compounds. The advantage of nanoparticles and nanosystems over homogeneous media consists in the effects of local proximity and preconcentration of the lanthanide ion and ligand components. This shortens the distance between the excitation energy donor and acceptor, increases the efficiency of energy transfer, and makes it possible to lower the limits of detection of fluoroquinolones by one to five orders of magnitude.

Comparing two types of nanoobjects—solid nanoparticles and liquid micellar nanosystems, it should be noted that the latter are more reliable in actual practice because surfactants are commercially available and micellization in water is a highly reproducible process. The use of micellar systems should ensure good reproducibility of the determination results and detection limits at a level of 10–10–10–8 M, which is significantly lower than the maximum permissible concentration of fluoroquinolones. The preparation of nanoparticles in each individual laboratory is still carried out according to an individual procedure, which depends on the nature of the reagents used, the temperature, the rate of synthesis, the growth time of nanoparticles, and the surface stabilizer used. Due to this multifactorial nature, the results obtained by different researchers can vary greatly. Further development of the commercial synthesis of nanoparticles and methods for their characterization and standardization may solve this problem in the future.