A Review on Analytical Techniques for Quantitative Detection of Biogenic Amines in Aquatic Products

Abstract

Aquatic products contain a large amount of protein, which can promote the production of a variety of biogenic amines through the function of microorganisms. Biogenic amines are a broad category of organic substances that contain nitrogen and have a low molecular weight. The presence of biogenic amines can cause the deterioration and excessive accumulation of aquatic products, which can cause damage to human health. Therefore, it is essential to discover a fast, convenient, and easy to operate method for the determination of biogenic amines in aquatic products. In this paper, the function and research significance of biogenic amines are analyzed from the aspects of their formation, toxicological properties, harm to the human body, and control methods. Several common direct detection techniques and indirect techniques for biogenic amines are briefly introduced especially sensors. This review provides references for efficient detection in the future.

1. Introduction

Aquatic products contain a large amount of protein. During the storage and transportation of aquatic products, microorganisms can decompose the protein to form amino acids. However, there are some potential safety issues with aquatic products, which may be major sources of heavy metals, persistent organic pollutants, parasites, microorganisms, and certain natural toxins [1]. In addition, during the drying process, lipids (triglycerides and phospholipids) in aquatic products are broken down by lipase to produce free fatty acids, which undergo additional oxidation to create a variety of aromatic compounds, including alcohols, ketones, and fatty aldehydes [2]. Free amino acids undergo decarboxylation reactions to produce biogenic amines. Biogenic amines are a class of compounds with low molecular weight and containing nitrogen. Basic details and chemical structures of a number of common biogenic amines are represented in Table 1. They have certain biological activity, which is widely found in diverse foods, including cheese, wine, meat, and aquatic products [3]. Trace biogenic amines are essential active ingredients in living organisms and have important physiological functions in living cells. They can promote the growth of organisms, monitor the production of nucleic acids and proteins, eliminate free radicals, and so on. However, if humans consume a great number of biogenic amines from aquatic products, or biogenic amines build up to significant quantities within the human body, they probably cause harm to human health, resulting in respiratory system issues, vomiting, headaches, cramping in the abdomen, and other adverse physiological reactions [4]. Normally, several enzymes in the human gut, such as diamine oxidase (DAO), monoamine oxidase (MAO), and polyamine oxidase (PAO), can degrade biogenic amines, thus avoiding excessive accumulation [5]. Among biogenic amines, histamine has the strongest toxicity, as it can bind to receptors on the cell membrane to produce toxicity. Tyramine is also highly toxic, and when ingested in excess, toxic phenomena such as migraines and high blood pressure can occur.

In both fermented and non-fermented products, biogenic amines are frequently found, such as cheese containing 5–4500 mg kg⁻¹. There are 2400–5000 mg kg⁻¹ biogenic amines in fish and beef liver, which contain biogenic amines of 340 mg kg⁻¹ [6]. For unfermented foods, biogenic amines can be used as a biomarker to analyze the decomposition of chemical components in food, as well as indicators of spoilage in certain foods. There is a detection index called the biogenic amine index (BAI), which can determine the character of seafood products and make the results have a certain degree of scientific and measurable validity. Its calculation formula is:

$$\begin{array}{l}BAI=({mgkg}^{-1}histamine+{mgkg}^{-1}putrescine\\ \hspace{1em}\hspace{1em}\hspace{1em}\hspace{1em}\hspace{1em}+{mgkg}^{-1}cadaverine)/(1\\ \hspace{1em}\hspace{1em}\hspace{1em}\hspace{1em}\hspace{1em}+{mgkg}^{-1}spermine+{mgkg}^{-1}spermidine)\end{array}$$

It is considered that there is some quality loss in the product when the BAI exceeds 10 [7].

All amines from different foods in a meal should be added up to determine the entire quantity of biogenic amines consumed rather than considering a single food separately. At the same time, when consuming different foods, the cumulative effects of different amines should also be considered. Therefore, many countries have strict intake standards for biogenic amines. Timely detection of excessive biogenic amines in aquatic products can effectively guarantee that they are safe to consume and have a good flavor [8]. Therefore, the development of a quick and precise detection technique to identify the categories and concentrations of biogenic amines has progressively drawn attention from researchers. There are several indirect detection methods, which mainly involve detecting biogenic amines by detecting the presence of amine-producing bacteria. In addition, chromatography, immunological recognition, enzymatic reaction, pH variation, fluorometry, biosensors, chemo-sensors, and optical chemo-sensor systems are used as the direct detection methods. Among them, sensors such as chemo-sensors have become popular in recent years for being fast, simple, and cost-effective. Although chromatography is widely used in practical applications, its high equipment cost and strict requirements for operators limit its application. Therefore, in recent years, sensors, especially chemical sensors, have become popular. Researchers can design and choose appropriate technologies according to different purposes, such as using pH sensors when only determining the presence or absence of biogenic amines. This method is fast, easy to operate, and easy to observe. If qualitative and quantitative detection of biogenic amines is required, nanomaterials can be considered. Due to the wide range of choices and the great application prospects of chemical sensors, continuous improvement of chemical sensor technology is a future trend for the efficient detection of biogenic amines.

The purpose of this review is to provide theoretical support for the efficient detection of biogenic amines in the future by introducing the formation, classification, hazards, and inhibition measures of biogenic amines, and by focusing on the detection methods.

Table 1. Information of main biogenic amines.

Biogenic Amine	Relative Molecular Mass	Classification	Precursor	Chemical Structures	Reference
Tryptamine	160.22	Heterocyclic Amine	Tryptophan		[9]
Histamine	111.15	Heterocyclic Amine	Histidine		[10]
Tyramine	137.18	Aromatic Amine	Tyrosine		[11]
β-Phenylethylamine	121.18	Aromatic Amine	Phenylalanine		[12]
Spermine	202.34	Aliphatic Amine	Arginine Ornithine		[13]
Spermidine	145.25	Aliphatic Amine	Arginine Ornithine		[14]
Cadaverine	102.18	Aliphatic Amine	Lysine		[15]

Table 1. Information of main biogenic amines.

Biogenic Amine	Relative Molecular Mass	Classification	Precursor	Chemical Structures	Reference
Tryptamine	160.22	Heterocyclic Amine	Tryptophan		[9]
Histamine	111.15	Heterocyclic Amine	Histidine		[10]
Tyramine	137.18	Aromatic Amine	Tyrosine		[11]
β-Phenylethylamine	121.18	Aromatic Amine	Phenylalanine		[12]
Spermine	202.34	Aliphatic Amine	Arginine Ornithine		[13]
Spermidine	145.25	Aliphatic Amine	Arginine Ornithine		[14]
Cadaverine	102.18	Aliphatic Amine	Lysine		[15]

2. Biogenic Amines in Aquatic Products

2.1. Classification and Sources of Biogenic Amines

There are several different classification methods for biogenic amines due to the differences in the structure of precursor amino acids, the quantity of amino acids, and the source of biogenic amines.

According to the structure of precursor amino acids, there are three types of biogenic amines, heterocyclic, aromatic, and aliphatic. Heterocyclic compounds include serotonin and histamine. Aliphatic compounds include agmatine, spermidine, putrescine, spermine, and cadaverine. Aromatic compounds include β-phenylethylamine and tyramine. Some aromatic amines, such as serotonin and tyramine, have vasoconstrictive functions, while others, such as histamine and 5-hydroxytryptamine, have vasodilatory functions.

The second classification method relies on the quantity of amino acids. Biogenic amines can be separated into monoamines, like tyramine, histamine, and serotonin; diamines, such as cadaverine and putrescine; and polyamines, including agmatine, spermine, and spermidine.

According to the source, there are two types of biogenic amines: endogenous amines and exogenous amines [16]. Tyramine and histamine play a role in hormone transmission. Dopamine and serotonin act as psychoactive mediators in the central nervous system, and they have certain functions.

Under low-temperature conditions, there is a noticeable number of histamines in marine fish. Cadaverine, histamine, and putrescine are among the various biogenic amines that are present in various aquatic products, including sardines, mackerel, tuna, and herring. There are still many amines in raw fish and its products, the content of which needs to be determined according to whether the fish is fresh or not [17]. Meat and meat products contain abundant proteins and amino acids. During storage, proteins undergo hydrolysis to form peptides. Peptides are not always stable. They then further degrade into oligopeptides and even free amino acids. Under the function of microorganisms, biogenic amines like spermidine, cadaverine, spermine, and histamine are generated [18]. The biogenic amines in dairy products mainly include histamine, tyramine, cadaverine, putrescine, etc., mainly through protein degradation and microbial action in dairy products [19].

2.2. Formation Mechanism and Influence Factors

Due to the action of microorganisms such as proteases, peptidases, and amino acid decarboxylases in aquatic products, proteins are broken down into amino acids, which then undergo decarboxylation reactions to generate biogenic amines. Figure 1 shows the specific procedure. However, some aquatic products do not contain amino acid decarboxylases. In this case, aldehydes and ketones undergo amination reactions with amino groups to generate biogenic amines [20]. In most cases, biogenic amines are formed through decarboxylation reactions under the action of amino acid decarboxylases. Substrate amino acids are exchanged through membrane anti-transporters in extracellular media, and then biogenic amines are synthesized in the cytoplasm. For example, if the exchanged substrate amino acid is tryptophan, serotonin will be synthesized in the cytoplasm [21]. Figure 2 shows the main formation process of biogenic amines. In general, though there are few exceptions, such as putrescine being comprised of arginine and cadaverine being comprised of lysine, precursor amino acid names typically match those of biogenic amines. For example, tyrosine is the source of tyramine, while histidine is the source of histamine.

Some internal and external factors affect the generation of biogenic amines, such as pH, temperature, oxygen supply, and water activity. At the same time, if there are inadequate hygienic conditions for processing and storing food, aquatic products are prone to microbial contamination and the production of biogenic amines. When hygiene conditions are poor, there are various microorganisms in the environment that can rapidly grow under suitable conditions. They may also interact with each other to accelerate the production of biogenic amines. Under temperature conditions, microbial growth, and enzyme activity were inhibited with the decrease in temperature, and the generation of biogenic amines was effectively reduced. When the temperature is too high, the bacteria that produce biogenic amines can be killed, which greatly inhibits the generation of biogenic amines [22]. The optimal temperature range is 20–37 °C [23]. For pH, biogenic amines are more easily produced under acidic conditions. The main reason is that the optimal pH of amino acid decarboxylase is 4.0–5.5. Therefore, under acidic conditions, the content of amino acid decarboxylase gradually increases, causing biogenic amines like tyramine, histamine, and putrescine to significantly increase in content [24]. Oxygen supply also has a great impact on the biosynthesis of biogenic amines. Various bacteria produce different amounts of biogenic amines under different oxygen supply conditions. For example, the amount of putrescine produced by Enterobacter cloacae significantly decreases under anaerobic conditions, while the amount of putrescine synthesized by Klebsiella pneumoniae is less, but the synthesis amount of putrescine has significantly increased under anaerobic conditions [25]. It is worth noting that these influencing factors do not exist alone but work together to promote or inhibit the production of biogenic amines. At the same time, biogenic amines are thermally stable, which means that if the raw material itself contains biogenic amines, they are difficult to remove when products are being heated up, such as pasteurization and cooking. Therefore, biogenic amines are easily absorbed by the human body, posing a health hazard.

2.3. Hazard of Biogenic Amines

The global demand for aquatic products is gradually increasing, but a large amount of waste may be generated during the processing of aquatic products [26]. Excessive intake or accumulation of biogenic amines in the human body can produce a variety of diseases or health problems. They can cause negative physiological responses, like abdominal cramping, headaches, palpitations, vomiting, respiratory system disorders, and other symptoms of poisoning.

2.3.1. Excessive Intake and Accumulation of Biogenic Amines

Normally, biogenic amines intake from aquatic products can be rapidly broken down through amine oxidase or binding, but if certain populations are allergic to biogenic amines or take drugs containing monoamine inhibitors, the normal decomposition process of biogenic amines can be disrupted, leading to their continuous accumulation in the human body [25]. For example, drinking alcohol or taking enzyme drugs and antidepressants that inhibit histamine metabolism are more likely to cause histamine poisoning in humans [19]. When only histamine is ingested if consumed in small amounts, it may not cause harm at lower levels, but sometimes the body may ingest multiple biogenic amines simultaneously. Interactions occur between different biogenic amines like cadaverine and putrescine, which can suppress the activity of histamine oxidase, thus increasing histamine content and enhancing the toxicity of food [19,27,28].

After ingesting biogenic amines, they may accumulate continuously in the body. When biogenic amines accumulate to a certain concentration that exceeds the body’s metabolic capacity, it can lead to biogenic amines poisoning. Histamine is the most toxic and can make blood vessels dilate, resulting in an obvious decrease in blood pressure. Next is tyramine, which can promote vasoconstriction. It can induce norepinephrine release and promote adverse reactions of histamine to increase blood pressure [29]. It is worth noting that various biogenic amines, combined with nitrogen, can produce carcinogens such as nitrite and enhance the poisonousness of tyramine and histamine [30]. For fish and other aquatic products, such as tuna, sardines, mackerel, salmon, etc., bacteria-rich muscle histidine in fish can multiply under appropriate temperatures, and the muscle histidine can be converted into histamine [31].

2.3.2. Poisoning of Biogenic Amines

Histamine poisoning, also known as scombroid fish poisoning, has the strongest toxic effect [31]. The main symptoms of poisoning include facial, neck, and upper arm flushing, urticaria, gastrointestinal symptoms, headache, and difficulty swallowing [32]. The incubation period of histamine poisoning is relatively short, usually 20–30 min, and the severity of symptoms is manifested as low or moderate [33]. Due to the fact that the symptoms of histamine poisoning are sometimes similar to allergy symptoms, histamine poisoning can be determined by measuring plasma histamine levels or whether high histamine foods have been consumed [34]. According to literature reports, the number of histamine poisoning cases caused by consuming tuna has been increasing year by year from 2014 to 2017 [33].

Tyramine poisoning, also known as cheese reaction, is characterized by elevated blood pressure, palpitations, and headaches, and it can occur 30 min after ingestion of food and several hours later [35]. Due to the potential interaction between monoamine oxidase inhibitors (MAOI) and tyramine toxicity, it is necessary to pay attention to whether the population is taking MAOI-related drugs [36]. Tyramine plays an important role in the gastrointestinal tract, and an increase in tyramine levels in the gastrointestinal tract may induce the release of inflammatory prostaglandins, leading to pro-inflammatory outcomes [37].

2.4. Control Methods for Biogenic Amines Excessive Accumulation in Aquatic Products

The methods for controlling excessive accumulation of biogenic amines are mainly through two methods: one is to avoid new biogenic amines appearing, and the other is to degrade the synthesized biogenic amines. Figure 3 shows the main control methods.

To inhibit the production of biogenic amines, three methods can be adopted: the first is to control the breakdown of amino acids, the second is to inhibit the propagation of microorganisms like amine-producing bacteria, and the third is to reduce the activity of amino acid decarboxylase.

For the propagation of producing amines bacteria and the activity of decarboxylase, one significant influencing factor is temperature, as both low and high temperatures can have significant impacts on decarboxylase and bacteria. At low temperatures, the enzyme bioactivity and growth of amine-producing bacteria decrease significantly. When ultra-low temperature conditions are reached, 5% to 30% of the water in the microbial cytoplasm begins to freeze, causing the concentration of cytoplasm to gradually increase [38]. When the temperature rises to 60 °C, the growth of amine-producing bacteria can also be inhibited [39]. WANG et al. [40] used brine immersion freezing (BIF) to treat tuna during the processing of canned tuna. The study found that yields of most bioactive substances were low at different stages of processing. Gardini et al. [41] found that low pH is also an effective method to inhibit the production of biogenic amines, and the generation amount increased with the increase in pH.

For canned aquatic products, various kinds of additives such as sodium chloride, sucrose, glucose, NaCl, glycine, lactic acid, citric acid, and sorbic acid were used to avoid the generation of biogenic amines. Food additives mainly inhibit the production of biogenic amines by suppressing the biological activity of amine-producing bacteria [42]. Jae-Hyung et al. [43] used seven different food additives, and the results showed that the glycine treatment group had the most significant decrease in the content of putrescine, cadaverine, and histamine.

Natural extracts such as cinnamon oil extract [44] can be added appropriately to effectively control the production of biogenic amines. In addition, Li et al. [45] found that natural proanthocyanidins have a significant inhibitory effect on putrescine, cadaverine, and tyramine, and this inhibitory mechanism is mainly achieved by affecting the undesirable microbial community and inhibiting microbial activity.

If aquatic products have been processed into canned products, it is difficult to directly remove the synthesized biogenic amines by using traditional refrigeration methods. Therefore, WANG et al. [40] studied the Maillard reaction of glucose with histamine by using fluorescence intensity and UV–VIS spectroscopy. Research has shown that the histamine content in canned tuna is significantly reduced, and the toxicity of Maillard reaction products is also significantly decreased.

2.5. Maximum Residual Limits of Biogenic Amines in Water Bodies

To ensure food safety, biogenic amine detection and management are essential. The safety standard for histamine in aquatic products varies from country to country. The US Food and Drug Administration (FDA) has defined a guidance level of histamine, and the limit of tyramine and β-phenylethylamine in aquatic products is 100–800 and 30 mg/kg [46], respectively. The EU regulates the healthy level of histamine for certain fish species at 100 mg/kg [46].

Table 2. Biogenic amine content of aquatic products (mg/kg).

Aquatic Products	Histamine	Cadaverine	Putrescine	Dopamine	Serotonin	Reference
Belt fish	2.6	24.2	15.9			[47]
Octopus	3.2	25.5	18.3			[47]
Common mackerel	1.9	1.4	0.4	<0.03		[48]
Common mullet	1.7	1.7	0.4	<0.03		[48]
Grass carp	2.51	0.90	1.32			[49]
Swimming crab	2.1	10.6	17.3	<0.1	0.1	[50]
Common sea squirt	3.4	18.7	12.5	<0.1	1.6	[50]
Chum salmon	1.4	<0.1	1.8	5.0	<0.1	[50]
Japanese scallop	<0.1	2.5	2.9	<0.1	<0.1	[50]
Silver pomfret	<0.1	<0.1	<0.1	<0.1	<0.1	[50]
Mackerel	2.3	4.8	0.9	1.6	1.2	[51]
Tuna	0.1	0.4	0.5	1.2	0.6	[51]

represents the content of various biogenic amines in common aquatic products.

3. Sample Pre-Treatment Technology

Sample collection, sample pre-processing, analysis and detection, data processing, and reporting results are the four main steps of a comprehensive sample analysis process. The statistical results show that sample pre-treatment in these four steps takes up a considerable amount of time, some even accounting for 70% or more of the entire process. Therefore, in recent years, research on sample pre-treatment methods and techniques has attracted the attention of analysts. The application of appropriate sample pretreatment technology can effectively improve the accuracy, precision, sensitivity, selectivity, and analysis speed of the analytical method, reduce or eliminate matrix interference, and is also conducive to the enrichment of target compounds. During the pre-treatment process, the reaction characteristics of the sample should also be considered. For aquatic products, because of the abundance of fats, proteins, and other substances they contain, selecting appropriate extractants is also crucial. They can dissolve biogenic amines and precipitate proteins. In recent years, as technology and materials continue to advance, sample pre-treatment technology has also been constantly updated and improved to be more accurate and effective for various sample analyses. Here are five sample pre-treatment techniques: QuEChERS (quick, easy, cheap, effective, rugged, safe) [52], solid-phase extraction (SPE) [53], liquid–liquid extraction (LLE) [54], dispersive liquid–liquid microextraction (DLLME) [55], solid-phase microextraction (SPME) [56]. Each of the five technologies has its own characteristics; for example, LLE uses a large volume of solvents that may further exacerbate environmental problems, while SPME does not require solvents during the extraction process [57].

Table 3. Advantages and disadvantages of different sample pre-treatment technology.

Sample Pre-Treatment Technology	Advantages	Disadvantages	Reference
Liquid–liquid extraction (LLE)	Minimal damage to the analyte; Easy to operate	Time consuming; Low extraction ability; High consumption of organic solvent	[58]
Solid-phase extraction (SPE)	Reduced analysis steps; Easy automation; Using no organic solvents	Time-consuming; Relatively expensive	[59]
Solid-phase microextraction (SPME)	Fast, universal; Solvent-less separation	Fibers used may be broken; Coating can be stripped off; Needle can be bent	[60]
Dispersive liquid–liquid microextraction (DLLME)	Easy to operate; Fast; High preconcentration factor; Environmentally friendly	High consumption of solvents; Partition coefficient decrease	[61]
QuEChERS	Easy to operate; Fast; High cost-effectiveness; Less equipment required; Relatively small amounts of solvents	Limited scope of application; Not very suitable for traditional fermented meat products	[62]

shows more characteristics of each pre-treatment technology.

3.1. Liquid–Liquid Extraction

LLE is extensively utilized in the fields of environmental, food, and biological analysis due to its simple equipment and operation [63,64]. When using the LLE method, salt-assisted LLE is often considered, as it does not need to be used with immiscible and toxic organic solvents, nor does it require severe mechanical oscillation [65]. Liu et al. [54] detected eight biogenic amines in wine using modified LLE; the limit of detection (LOD) and quantification (LOQ) were 0.001–0.050 mg/L and 0.005–0.167 mg/L, respectively. What’s more, the detection time is effectively shortened, the amount of organic reagents is reduced, the cost has been effectively controlled, and the operation is simple and fast, with strong practicality.

3.2. Solid-Phase Extraction

SPE can be divided into the following categories: ion exchange SPE, reverse phase SPE, normal phase SPE, and mixed-mode SPE. The most appropriate method can be selected according to the characteristics of the seafood to be tested and the type and characteristics of different biogenic amines. For example, the interaction force in an aqueous phase sample is mainly van der Waals forces, and thus, reverse phase SPE can be used. The main advantages of SPE include a high recovery rate, reduced analysis steps, shortened analysis time, easy automation, compatibility with chromatographic analysis, and reduced use of organic solvents [66]. Sagratini et al. [53] determined eight biogenic amines, including spermine, cadaverine, spermidine, and so on, in fish; the LOD and LOQ were 0.02–0.25 mg/kg and 0.07–0.75 mg/kg.

3.3. Solid-Phase Microextraction

SPME is a relatively new and easily automated technology used for extracting analytes from gas, liquid, and solid matrices [56]. SPME overcomes the disadvantages of traditional sample pre-treatment techniques. It can integrate sampling, extraction, concentration, and injection, greatly accelerating the rate of analysis and detection. Its significant technological advantages are extensively utilized in fields including food, pharmaceutical industry, and environmental analysis. Headspace SPME (HS-SPME) is extensively used for the preparation and analysis of complex samples. This technique has low matrix interference clear spectra and can protect fibers from irreversible damage, which is caused by non-volatile coexisting compounds present in complex matrices [40]. Chen et al. [67] designed a functionalized mesoporous silica-coated SPE Arrow system to determine six biogenic amines, and the results showed that the LOD and LOQ were 1.1–26.8 μ g L⁻¹ and 3.5–89.3 μ g L⁻¹, respectively. HS-SPME is also applied to extract and determine the contents of putrescine, histamine, and tyramine in canned aquatic products. Figure 4 shows the application of SPME in recent years.

3.4. Dispersive Liquid–Liquid Microextraction

DLLME is environmentally friendly, fast, simple, and easy. Figure 5 shows the basic process of applying the DLLME method, with red wine as the sample. Zhang et al. [55] used CHCl₃ as the extractant, and the dispersant was methanol. The results showed that the linear relationship performs well. The LOD and LOQ were at a low level, which was 1.77 and 5.33 μ g kg⁻¹, respectively.

3.5. QuEChERS

QuEChERS is a widely used sample pre-treatment technique, which is essentially a sample pretreatment method formed by a combination of oscillation extraction, LLE for preliminary purification, and matrix dispersion SPE for purification. Compared with traditional methods (LLE, SPE), the QuEChERS method has many advantages, such as simple and fast operation, high cost-effectiveness, less equipment required, use of inert materials and relatively small amounts of solvents, etc. [62]. Guo et al. [52] researched the pollution characteristics of seven biogenic amines in eight types of canned sea fish samples. The study used carbon sphere QuEChERS mixed dispersion SPE coupled with high-performance liquid chromatography (HPLC) to analyze and determine the samples. The experimental data indicated that the experiment had a high recovery rate (92.3–97.7%), LOD, and LOQ of seven biogenic amines were 7.2–10.8 mg/kg and 24–36 mg/kg, respectively. Therefore, with this technique, biogenic amines in canned fish can be accurately detected.

4. Detection Techniques of Biogenic Amines

With the advancement of technology, there are diverse methods for detecting biogenic amines, including direct and indirect detection methods. The indirect detection methods do not directly identify biogenic amines but rather measure the activity of amine-producing bacteria. This type of method is extremely unstable and susceptible to various factors, such as the environment. On the contrary, direct detection methods yield more accurate results and can classify different biogenic amines with higher credibility. This review mainly introduces several specific methods for detecting biogenic amines. Figure 6 shows the classification of several detection methods in this review.

4.1. Indirect Detection Technique of Biological Amines

The type of biogenic amines in aquatic products can be judged indirectly by detecting the amount and type of bacteria that can produce amines, including microbiological and molecular biology methods. Compared with the direct detection technology of biogenic amines, indirect detection technology is fast and simple, but its accuracy and specificity are poor. In addition, finding amine-producing bacteria does not always mean that a biogenic amine in aquatic products is present, and even if it is, it is unclear how much. The generation of biogenic amines is also influenced by environmental factors.

4.1.1. Microbiological Method

Proteins in aquatic products are broken down by microorganisms, such as proteases and peptidases, to form amino acids and other chemical substances. Free amino acids undergo decarboxylation reactions to produce biogenic amines. Therefore, indirect detection technology can determine biogenic amines by detecting the categories and quantities of microorganisms present in aquatic products. If amine-producing bacteria can grow in food, then it is highly likely that biogenic amines will be detected. When biogenic amines degrade, they can restrain the reproduction of harmful bacteria, degrade nitrites, and provide a good taste [68]. In aquatic products, the main amine-producing bacteria are Hafnia alvei, Klebsiella variicola, Proteus vulgaris, Morganella psychrotolerans, Morganella morganii, Pantoea agglomerans, Enterobacter aerogenes, Photobacterium phosphoreum, Acinetobacter baumannii, which are all Gram-negative contaminants [21]. Generally, selective culture media are used to identify amine-producing bacteria, and then alkaline biogenic amines are stained with the acid–base indicator bromocresol violet to screen for amine-producing bacteria [69]. However, there may be some alkaline metabolites [70] in the medium, which are produced by the complex metabolic processes of microorganisms. They can affect the identification results and cause false positives, so it is necessary to adjust the composition of the culture medium according to the specific type of biogenic amines. Therefore, although microbiological methods can detect biogenic amines, they have significant limitations and are susceptible to external interference.

4.1.2. Molecular Biology Method

Compared with traditional methods, molecular biology methods are rapid, scientific, and reliable, and no culture is required. Before biogenic amines are produced, it can predict whether a food will produce biogenic amines [71]. Multiple PCR technology has become increasingly popular in recent years, and it can simultaneously and rapidly detect multiple amine-producing bacteria [72]. In raw fish products, histamine can be produced because Gram-negative bacteria are present in the gut. The histamine in tuna and mackerel is produced by the decarboxylation of histidine decarboxylase (HDC), which exists in muscle tissue during the breakdown process [71]. Therefore, it is essential to efficiently detect bacteria that can produce histidine in order to prevent microbial invasion and reproduction and high-level histamine production during the storage and processing of aquatic products [71]. Takahashi et al. [73] designed a technique by PCR for rapid determination of bacteria that can generate histamine and is Gram-negative. What’s more, they used single-strand conformation polymorphism (SSCP) technology to analyze the amplification products of the HDC gene for identification. The method collected 37 strains that can produce histamine and 470 strains that cannot produce histamine from fish and determined their histamine formation content using paper chromatography. Strains of P. phosphoreum, Proteus vulgaris, E. aerogenes, Enterobacter amnigenus, M. morganii, R. planticola, Hafnia alvei, P. damselae were positive by detecting by PCR, while the 470 strains that cannot produce histamine did not produce any amplification products.

Table 4. Primers used in the PCR assay.

Primer	Target Gene	Sequence	Amplicon Size (bp)
PUT1-F	ornithine decarboxylase	TWYMAYGCNGAYAARACNTAYYYTGT	1440
PUT1-R	ornithine decarboxylase	ACRCANAGNACNCCNGGNGGRTANGG	1440
HIS1-F	histidine decarboxylase	GGNATNGTNWSNTAYGAYMGNGCNGA	372
HIS2-R	histidine decarboxylase	TANGGNSANCCDATCATYTTRTGNCC	531
TDC-F	tyrosine decarboxylase	TGGYTNGTNCCNCARACNAARCAYTA	825
TDC-R	tyrosine decarboxylase	ACRTARTCNACCATRTTRAARTCNGG	825

presents some primer-related information used in the PCR assay.

4.2. Direct Detection Technique of Biological Amines

4.2.1. Chromatography

Chromatography can be used to determine the amounts of biogenic amines present. The following six common chromatographic detection techniques are introduced. They are high-performance liquid chromatography (HPLC), liquid chromatography (LC), ion chromatography (IC), capillary electrophoresis (CE), thin-layer chromatography (TLC), and gas chromatography (GC).

High-Performance Liquid Chromatography Method

The method most frequently employed for quantitative analysis of biogenic amines is HPLC, which can detect biogenic amines sensitively and obtain scientific and reliable data. Each component in a mixture can be identified, separated, and quantified using this method. An HPLC–MS/MS method was established by Nalazek-Rudnicka et al. [74] to identify biogenic amines in alcoholic beverages (beer and wine). It was derivatized with tosyl chloride. The technique had high sensitivity and good reproducibility. In this manner, the majority of biogenic amines can be found. Fu et al. [75] identified eight biogenic amines in aquatic products using HPLC. The findings demonstrated that there was a good linear relationship (r² > 0.999) among phenylethylamine, tryptamine, spermidine, histamine, putrescine, and cadaverine. The maximum LOD value for eight biogenic amines is 0.021 mg kg⁻¹, and the minimum value is 0.007 mg kg⁻¹. The LOQ value range of eight biogenic amines is 0.024–0.069 mg kg⁻¹. The spiked recovery rate was basically between 68% and 123%, indicating that this method can be considered when detecting biogenic amines in multiple aquatic products at once. During the operation of HPLC, due to the lack of suitable chromophores for most biogenic amines, derivatization with reagents such as dansyl chloride (Dns-Cl) and o-phthalaldehyde (OPA) is necessary before the detection of fluorescence or ultraviolet. However, the derivatization process of the current approach is time-consuming and laborious, and the price of Dns-Cl is relatively high [76,77].

Liquid Chromatography Method

The LC method is a commonly used method for detecting biogenic amines, second only to the HPLC method, and it also has high accuracy, sensitivity, and selectivity [78]. The mechanism of separation of LC is grounded in the different partition coefficients of all of the mixtures in the fixed phase and the mobile phase. LC has three categories, including liquid–solid chromatography, liquid–liquid chromatography, and bonded phase chromatography, which are mainly different from stationary phases. In addition, because of the different types of stationary phases, LC is classified into column chromatography, paper chromatography, and thin-layer chromatography. LC with pre- or post-column is mainly applied to biogenic amine separation and quantification [79]. Veciana-Nogues et al. [80] established a post-column derivatization LC method for biogenic amines detection in fish and its products. The method regulated the column and post-column apparatus for reactions under the condition of room temperature. The experiment chose 1 mL/min as the mobile rate of flow, and 0.5 mL/min was used as the derivatization reagent rate of flow. The findings demonstrated that the range of linear of various biogenic amines was 0.25–8.00 mg/L (r² > 0.992), and the recovery rate was between 92% and 103%, indicating that the method has certain accuracy and reproducibility.

The LC–MS method combines liquid chromatography with mass spectrometry. The benefit of using LC–MS is that it does not require derivatization, but it has high instrument costs and strict requirements for operators. Kosma et al. [81] determined β-phenylethylamine, cadaverine, putrescine, histamine, tyramine, and serotonin in trout samples frozen for 15 days. The experimental data indicated that on the 15th day, the concentration of serotonin, histamine, putrescine, and cadaverine was higher at 76.530 mg kg⁻¹, 85.530 mg kg⁻¹, 25.210 mg kg⁻¹, and 15.975 mg kg⁻¹, respectively, while β-phenylethylamine and tyramine had lower content, at 3.230 mg kg⁻¹ and 0.165 mg kg⁻¹, respectively. There is a commercially available derivative reagent, 2,4,6-triethyl-3,5-dimethyl pyrylium trifluoromethane sulfonate (Py-Tag), which can be applied to aquatic products to detect biogenic amines. The significant advantages of Py-Tag include improved sensitivity, short reaction time, and minimal odor [82]. However, the drawback is the narrow range of biogenic amines that can be detected [83]. Py-Tag can selectively react rapidly with primary amine groups on carbon chains containing two or more carbon atoms under alkaline conditions [84]. Figure 7 shows the derivative products of histamine and Py-Tag after derivatization. The experiment showed that the spiked concentration of the sample was from 88% to 104%, and the relative standard deviation was less than 6.1%. The detection of specific biogenic amines can be accomplished with this technique.

Thin-Layer Chromatography Method

TLC plays a great role in quickly separating and qualitatively analyzing small amounts of substances. Aladhadh et al. [85] determined several biogenic amines (spermine, cadaverine, spermidine, tyramine, histamine, and putrescine) in fish from retail stores by TLC method; the experience showed that the content of putrescine (17.28 mg/kg) and cadaverine (10.26 mg/kg) in frozen shrimp was high. Sardines in spicy tomato sauce contained less total biogenic amines, which is about 3.19 mg/kg. Spermidine, spermine, and tyramine were not detected in Jon West salmon. According to the research findings, different aquatic products have varying amounts of biogenic amines. Valls et al. [86] used five different layer solvents, including (a) a mixed solution of ethanol and ammonia, (b) a mixed solution of methanol and ammonia, (c) a mixed solution of chloroform and n-butyl acetate, (d) a mixed solution of chloroform, methanol, and ammonia, and (e) a mixed solution of acetate and ammonia. The separation result of acetone: ammonia solvent, the proportion is 95:5, was the best. Estimating the amount of certain biogenic amines in a sample can be done by comparing its Rf, shape, size, and color. The concentration range that TLC can estimate in this experiment was: the cadaverine content in salted and dried fish was 5–40 mg%, the tyramine content was 10–20 mg%, and the cadaverine, serotonin, and histamine contents in canned fish was 10–20 mg%, 5–10 mg%, and 10–60 mg%, respectively. Therefore, the TLC method can qualitatively and quantitatively analyze biogenic amines in mixtures.

Gas Chromatography Method

By using the various physical characteristics of substances, such as their adsorption capacity, affinity, solubility, and blocking effect, GC is a technique for separating and analyzing different elements in a mixture. Badrul et al. [87] used a GC-flame ionization detector (GC-FID) to detect heptylamine, tyramine, histamine, spermidine and cadaverine in fish, and confirmed the structure of biogenic amines using MS. It can be inferred by experiment that the LODs range of the five biogenic amines were 1.2–2.9 µg/mL, and the LOQs range were 3.98–9.65 µg/mL. High histamine concentrations (5.96 µg/mL) were detected in mackerel, while tyramine was the most detected in this study. In addition, the experience also showed that biogenic amines in fish did not accumulate all the time because of the presence of salt, and the process was effectively inhibited. At the same time, it had a certain preservative effect. Shalaby [88] found that sodium can restrict the accumulation of biogenic amines, and 2% sodium hexametaphosphate can delay the production of histamine. Mah and Hwang [43] revealed that adding salt to vitamin products can lower quantities of biogenic amines. Bonilla et al. [89] studied the “cold on column” GC method for analyzing cadaverine and putrescine, which did not require derivatization treatment. Prepare the tested biogenic amine into a standard mixture and inject it into the GC system 14 times, keeping the chromatographic conditions consistent throughout the experiment. According to the chromatogram, it was found that putrescine was eluted first, which took 6.073 min. Then heptylamine was eluted at 6.638 min, and finally, cadaverine was eluted at 7.031 min. In addition, the experiment had good reproducibility and quantitative analysis results.

Ion Chromatography Method

The principle of IC is to separate the anions and cations present in food at the same time through ion exchange and then carry out qualitative and quantitative analysis. For example, a low-capacity cation exchange resin is poured into the separation column, and an eluent solution of hydrochloric acid is used to analyze cations. At low pH values, all analytes are ionic, making this method especially appropriate for the polar amine analysis [90,91]. Kocar et al. [92] combined IC with MS to detect histamine in aquatic products and separated it using a cation exchange column. This method did not require additional derivatization operations, only pure water ultrasound for 5 min and vortex for 25 min for extraction. Then, by comparing the results with the HPLC detection results, researchers finally conducted a correlation analysis between the two. The experimental results indicated that the histamine content in fresh anchovy (sample 1) detected by IC–MS/MS was 4.51 ± 0.67 mg/kg. In 15% saline-treated anchovy (sample 2), it was 2.59 ± 0.98 mg/kg. In Danish fermented herring (sample 3), it was 11.25 ± 0.49 mg/kg. In Norwegian smoked salmon (sample 4), it was 1.67 ± 0.09 mg/kg. Using HPLC to detect histamine, the contents from sample 1 to sample 4 were 3.45 ± 0.02, 2.42 ± 0.03, 8.98 ± 0.36, and 1.81 ± 0.06 mg/kg, respectively. In addition, according to the correlation analysis, significant similarities were found in 56% of the results (p > 0.05). However, it was found that the correlation between IC–MS/MS and HPLC was poor when detecting other biogenic amines, and further research is needed.

Capillary Electrophoresis Method

CE is a novel form of technology for liquid-phase separation that uses capillary tubes as separation channels and requires an electric field powered by high-voltage direct current to provide power, ensuring the normal operation of the instrument. CE is used for detecting biogenic amines, with simple sample preparation and easy separation but low sensitivity. Therefore, a method combining CE with magnetic solid phase extraction (MSPE) was designed to improve detection sensitivity [93]. At the same time, a new type of MSPE adsorbent was used in the experiment, and Pt–Co–MWCNTs–COOH was created by combining the new magnetic field material Pt–Co with multi-walled carbon nanotubes (MWCNTs), where –COOH can provide more biogenic amine recognition sites for the adsorbent. The results demonstrated a strong linear relationship between peak area and biogenic amine concentration. The intra-day and inter-day precision of peak area was 1.3–9.0% and 2.2–9.6%, respectively. For migration time, the intra-day precision was 0.2–0.8%, while the inter-day precision was 0.7–1.4%, indicating that the accuracy of the MSPE–CE method was effectively improved. Similarly, molecular imprinting solid-phase extraction (MISPE) technology is combined with CE to detect histamine in food [94]. This method prepared a highly selective molecularly imprinted polymer (MIP) as an adsorbent, which has specific recognition sites. The results showed that the LOD and LOQ were 0.087 µg/L and 0.29 µg/L, with good repeatability. These experiments fully consider the limitations of the CE method and combine it with other techniques to improve the shortcomings of the technology itself, simplify sample pretreatment, and thus detect biogenic amines more sensitively and accurately.

4.2.2. Biosensors

A biosensor comprises molecular recognition elements, signal conversion parts, and processors [95]. The working mechanism of a biosensor is to first identify the target analyte and then generate a signal, which is then transformed into signals electrically by the signal conversion part. Certain physical or chemical changes can be caused by the primary functional components, such as microorganisms, enzymes, nucleic acids, and antibodies. In most cases, they can achieve a selective recognition function. The component that converts biological activity signals into electrical signals is a chemical or physical transducer. The output of biosensors is usually magnetic, mechanical, electrical, optical, or thermal signals while also considering whether the detection system is compatible with the sensor platform [96].

Enzymatic Reaction

The principle of using enzyme biosensors to detect biogenic amines is the assimilation of the biosensing electrode near the enzyme. Enzymes have two forms of action: producing electroactive substances or consuming electroactive reactants. In addition, enzyme biosensors can be separated into two kinds: inhibitory sensors and substrate sensors. Substrate biosensors usually assess target substrates and their enzyme reactions, while inhibitor biosensors typically evaluate the reducing activity of substances or enzymes [95,97,98]. Enzyme-based chemiluminescent biosensors have the advantages of speed, wide linear range, ease to operate, low LOD, and no need for monochromatic light [99]. Obervic-Miklikanin and Valzacchi developed two luminescent biosensors based on DAO and putrescine oxidase. Based on the findings, the linear range of the two biosensors was 1–2 mg/L. The LOD of putrescine oxidase biosensors was 0.8 mg/L, and the LOD of DAO biosensors was 1.3 mg/L [100]. Metal nanoparticles (NPs), including gold, platinum, molybdenum, and silver, as well as carbon nanoparticle materials, are known as nanoenzymes. They were widely used in the progress of nanoenzyme-based biosensors for detecting pollutants in food [101]. Kuo et al. [102] developed a sensor according to Ag/Au NPs. Spermine can be detected in urine samples using the sensor, and it can exhibit peroxidase-like and oxidase-like catalytic activity. The findings of the experiment showed that the Ag–Au/AgCl nanosensor exhibited highly efficient catalytic activity, with a linear range of 2.6 nM–8.0 μM and LOD of 0.87 nM. Figure 8 illustrates the basic principle of Ag/Au NPs synthesis.

Sanz-Vicente et al. [103] designed an enzyme colorimetric analysis system to detect biogenic amines in tuna samples. The system uses tyramine oxidase (TAO) as the molecular recognition part and can simultaneously detect histamine and tyramine under pH = 8 conditions. Tyramine could be detected within 30 s, while histamine detection took about 4 min. In addition, the system was also connected to smartphones and did not require specialized training during use. It consumed fewer reagents and was a portable and green detection method.

Immunological Recognition

The principle of immune recognition is to use biogenic amines as antigens and utilize biological components of recognition such as antibodies [104], nucleic acid aptamers [105], molecularly imprinted polymer (MIP) [106], etc., to bind with antigens for the detection of biogenic amines content. Because of its simple structure, histamine cannot stimulate the production of specific antibodies and usually requires derivatization. In recent years, MIPs have been widely used as biological recognition components for detecting biogenic amines due to their stability, robustness, and specific recognition ability. Venkatesh et al. [107] demonstrated a flexible histamine sensing device that can be used to detect histamine in aqueous media, and its mechanism of action was based on impedance spectroscopy and MIP. What’s more, they developed a portable smartphone that was a semi-quantitative histamine sensing device in various aqueous solutions and seafood.

Research has shown that many antibodies against histamine derivatives have been prepared. However, the reaction time for preparing antibodies is relatively long, and side reactions may occur during the experimental process. These issues need to be improved. Xu et al. [108] used enzyme-linked immunosorbent assay (ELISA) to conjugate histamine with fetal bovine ovalbumin or serum albumin as antigen and then injected the conjugate into the subcutaneous tissue of mice. Indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was used to detect the titer of the antiserum. The experiment could establish a standard curve to determine drug remnants, but the disadvantage was that it took a long time to carry out the whole detection [109]. The research results showed that the IC₅₀ value was 1.2 μ g/mL, indicating that the antibody could be used for histamine detection. The LOD (IC₁₀ value) was 89.0 ng/mL, and the range of linear was 100.0 ng/mL to 10.0 μg/mL.

If antibodies are used as biological recognition elements to form an immunosensor, the specificity of the sensor is strong due to its strong antigen–antibody reaction binding ability. Shkodra et al. [110] developed a novel immunosensor for histamine detection, which is according to single-walled carbon nanotubes (SWCNTs). After oxygen plasma treatment, histamine is competitively reacted with horseradish peroxidase (HRP)-coupled histamine and antihistamine antibodies. The results indicated that the detection range of histamine using this method was 0.5–50 ng/mL, and the method had high specificity and sensitivity.

4.2.3. Chemo-Sensors

Electrodes and chemical modification of the electrodes are necessary using chemical sensors to detect biogenic amines [111]. Platinum, gold, carbon, and silicon are frequently employed to identify biogenic amines in food and beverage samples [112]. For example, carbon nanotubes (CNTs) have a wide range of applications because of their high chemical and thermal stability [113]. Chemical sensors mainly consider electrochemical sensors, which are fast, simple, and cost-effective. The receptors of electrochemical sensors can be divided into chemical and biological categories; that is, the receptors are chemically or biologically modified, and then the receptors react with the analyte, generating electronic signals from an individual or a collection of analytes to obtain relevant data [112]. There are various methods for modifying receptors to generate electrical signals, such as current analysis, impedance analysis, and potentiometric analysis [114]. The current analysis method determines the concentration of the component by measuring the current generated by the measured component. The potential analysis method includes an electrode that is used to work and a reference electrode, which determines the concentration of the measured component by measuring the potential difference between the two. The impedance method determines the impedance from the analyte, including resistance and reactance.

Nanomaterials

In recent years, metal nanomaterials have become increasingly popular for testing and analysis of food safety. These materials possess distinct optical, electrical, physical, and chemical characteristics; additionally, their size, shape, structure, and surface characteristics can be altered [115]. The specific identification of biogenic amines is a common application for gold nanoparticles, nanorods, and nanoclusters. Du et al. [116] used a colorimetric chemical sensor array according to gold nanoparticles to detect the biogenic amine content produced while the raw fish was deteriorating (tuna). In the experiment, three carboxylate derivatives were used, including 11-mercaptodecanoic acid (S1), 4-mercaptobenzoic acid (S2), and 6-mercaptohexanoic acid (S3), to functionalize AuNPs. AuNPs functionalized with longer alkyl chains of 11-mercaptodecanoic acid can detect high concentrations of analytes [117]. When AuNPs came into contact with biogenic amines due to cross-reactivity interactions, aggregation-induced ultraviolet-visible (UV–VIS) spectral changes resulted in significant color changes in the solution. This experiment prepared two types of AuNPs (IS–AuNPs and DS–AuNPs), where IS–AuNPs were prepared by mixing Na₃Ct (0.65 mmol, 2 mL) with HAuCl₄ (0.25 mmol, 98 mL), while DS–AuNPs were prepared by mixing Na₃Ct (0.65 mmol, 99 mL) with HAuCl₄ (0.25 mmol, 1 mL). The experimental results showed that after surface functionalization with S1, S2, and S3, a slight spectral shift was observed in the extinction spectrum of IS–AuNP and its deep red color could be used for colorimetric sensors. The concentration of histamine gradually increased over time, while there was little change in spermidine and spermine concentrations. Through this method, biogenic amines can be qualitatively and quantitatively analyzed from mixtures and can also be used to detect freshness.

Due to the different aggregation behaviors of target biogenic amines, Abbasi-Moayed et al. [118] utilized AuNP and AgNP to create unique plasma patterns for each biogenic amines to detect and distinguish four biogenic amines, including spermine, spermidine, histamine, and serotonin. Due to the different compositions of AuNP and AgNP, there were significant differences in the color changes produced when exposed to different biogenic amines. Four biogenic amines were classified using principal component analysis–linear discrimination analysis (PCA–LDA). Furthermore, a colorimetric sensor array was designed to accurately distinguish between individual biogenic amines and their mixtures. The experimental results indicated that spermine and spermidine induced rapid aggregation of AuNPs, but they showed significant differences in the aggregation level of AgNPs, which could be used to distinguish spermine and spermidine. Serotonin and histamine hardly caused aggregation of AgNPs, while AuNPs exhibited significantly different aggregation, which could be distinguished by serotonin and histamine. From a color perspective, AgNP has turned from yellow to orange, and AuNP has turned from red to purple. Therefore, this method can distinguish biogenic amines intuitively, quickly, and simply due to the obvious color changes.

Cao et al. [119] developed a nanosystem for ratiometric fluorescence according to upconversion nanoparticles (UCNPs) for efficient detection of histamine in aquatic products. It acted exclusively on histamine by using diazonium ions as a selective chromogenic agent. A combination of azo reagents produced diazonium ions. During this process, UCNPs went through signal transduction. UCNPs have high chemical stability, non-spontaneous fluorescence, and great capacity to penetrate light, and can be used as fluorescent markers in assays [120]. This experiment selected different concentrations of histamine as samples, namely 0, 5, 10, 15, 20, 25, 50, 75, 100, 125, 150, 175, and 200 mg/L, and then added them to Na₂CO₃ and UCNPs solutions, followed by the addition of mixed azo reagents. Finally, the detection of colorimetric and upconversion fluorescence was achieved at room temperature. The experimental results indicated that in the separated emission and absorption spectra within the mixed nanosystem, the two primary fluorescence peaks of UCNP were located at 548 and 664 nm. If histamine was further added, a fresh absorption peak emerged at 548 nm and kept growing until it crossed over with the emission peak of upconversion fluorescence. Therefore, the luminescence intensity ratio I₅₄₈/I₆₆₄ can be applied to ascertain the content of histamine.

pH Sensors

Detecting biogenic amines through pH sensors is a direct, convenient, and easy to observe method. Biogenic amines contain nitrogen elements and have a small molecular weight; they are mostly alkaline. Therefore, pH indicators such as anthocyanins, curcumin, bromophenol blue, bromocresol green, methyl red, etc., can effectively detect biogenic amines. When biogenic amines are present in aquatic products, color changes may appear, and a pH sensor can clearly show this change. Although this method is convenient for observation, it cannot accurately measure the content of biogenic amines and can only provide semi-quantitative information. Usually, the sensitivity is relatively low. Siripongdera et al. [121] used pH-sensitive infectious materials with a pH range of 5.2–6.8 as sensing elements to establish a colorimetric and LDI–MS dual detection platform for screening and quantitative detection of biogenic amines. This method selected bromocresol purple as the pH indicator to make a colorimetric sensor. The initial color of the sensor was yellow, and if it came into contact with alkaline biogenic amines, the color turned purple. The experimental results showed that after 30 min, the sensor for detecting cadaverine underwent a color change. At 8 h, the sensor turned purple instead of yellow when it detected putrescine. Zhong et al. [122] studied a colorimetric sensor array for detecting biogenic amines, which was made of a composite of pH-sensitive infectious materials and nanomaterials. The study showed that due to the existence of functional groups that were acidic on the exterior of nanomaterials, it was easy to combine with alkaline biogenic amines. The concentration of amine vapor generated by the nanoporous structure of nanomaterials/dye composites or substrates, a good linear detection range, and a detection limit were obtained. In addition, the reaction time was effectively shortened. Ding et al. [123] introduced cellulose into polyvinyl alcohol (PVA) and developed a pH sensor for detecting biogenic amines in spoilage shrimp. The color changed from yellow to brown, indicating the strong operability of the sensor. Therefore, using pH sensors to detect biogenic amines has great application prospects, and it can be considered to combine it with other materials for qualitative and quantitative analysis.

Fluorometry

Roth first proposed the use of OPA and reduced agents such as 2-mercaptoethanol (2-ME) to detect primary amino compounds [124]. However, traditional fluorescence detection equipment is expensive, takes a long time to analyze, has low sensitivity, and cannot qualitatively and quantitatively determine the total amount of biogenic amines in food. Therefore, Hasanova et al. [125] designed a fluorescent DTE AuNP/OPA (DTE: 1,4-dithioerythritol) method based on NPs in order to identify biogenic amines. The principle is that under alkaline conditions, one thiol group of DTE is covalently bound to AuNPs, while the other group of –SH is available and participates in the indole reaction between OPA and primary amines. The results showed that the emission spectra of histamine, 2-phenylethylamine, serotonin, and tyramine under 340 nm excitation exhibited a good linear relationship. The LOD range was between 4.20 and 27.1 nM, and this method effectively detected the total biogenic amine content with high operational feasibility. Peat et al. [126] combined a reverse-phase HPLC system with fluorescence to detect the levels of trypsin, 5-hydroxyindoleacetic acid (5-HIAA), 5-hydroxytryptamine (5-HT), dopamine, and norepinephrine in the rat brain. The research indicated that the optimal settings for simultaneously measuring these five substances were a wavelength of excitation of 290nm and a wavelength of emission of 330nm. Norepinephrine had the highest recovery rate (98%), followed by 5-HT, and 5-HIAA had the lowest recovery rate (90%). In addition, through this experiment, the 5-HT content was 1.2 ± 0.13 (n = 6) ng/mg wet tissue, the concentrations of dopamine and 5-HIAA were 7.9 ± 0.68 (n = 6) and 1.3 ± 0.13 (n = 6) ng/mg wet tissue, respectively.

A fluorescent probe CMA–Cl derived from coumarin derivatives was designed and synthesized to detect biogenic primary diamines such as cadaverine and putrescine [127]. Among them, diethylaminocoumarin is a multifunctional fluorescent group. It has some significant advantages, such as more fluorescence quantum, good light stability, and a simple synthesis process. Its visible light range absorption and fluorescence spectra made it useful for visual observation and biogenic amine detection. The detection principle of this fluorescent probe is due to the fact that primary diamines have two groups of amino acids, which can be specifically recognized by aldehyde and chloroquine groups on CMA–Cl and then undergo reactions involving nucleophilic substitution and condensation, causing significant changes in fluorescence intensity. The experimental results showed that the addition of cadaverine at 475 nm exhibited strong blue fluorescence, while the fluorescence intensity varied with the addition of other biogenic amines, indicating a certain selectivity for different biogenic amines. Based on this, the experiment also prepared CMA–Cl loaded test strips to track the content of biogenic primary diamines during fish spoilage. As the exposure time of fish samples to air increases, the degree of spoilage gradually increases, and the biogenic amines concentration gradually increases. The color of the test paper changed from yellow to white, which could achieve convenient and rapid detection of biogenic amines.

In addition, multi-functional molecular assemblies can be used to develop chemo-sensor. Among them, porphyrins can be used as colorimetric and fluorescent chemo-sensor due to their multiple binding sites and unique photophysical properties. Guo et al. [128] introduced a ditopic porphyrin-based chemo-sensor for detecting histamine, which was prepared from tetraphenylporphyrin (TPP) by adding a second binding site during the β–pyrrole functionalization strategy. This sensor had two receptor sites; one was carboxylic acid, and the other was metal zinc ion, which had a strong affinity for histamine and high binding constants. By using sensors to separately identify histamine, histidine, and nicotine, and according to the roughly linear correlation between each component’s concentration and the emission peak ratio, it can be found that histamine was the most sensitive for identification.

Optical Chemo-Sensor Systems

Optical sensors mainly rely on the measurement of absorption rate, while fluorescent sensors combine with specific recognition elements to quantitatively analyze the intensity of fluorescence signals [129]. The absorption ability of biogenic amines in the visible light range is weak because they lack conjugated aromatic π–electron systems and do not have chemical structures that can be used for optical detection [130]. It is usually difficult to directly detect biogenic amines through optical sensors. Therefore, in order to obtain ideal detection performance and make it suitable for optical analysis, it is essential to use chromophores or fluorophore to derive bioamines and convert them into corresponding derivatives [131]. Optical sensors are appropriate for in vivo measurements and remote sensing, even at distances greater than kilometers. A portable sensor system or dipstick sensor has been designed based on various probes, such as reflectometry, luminescence, photometry, surface-enhanced Raman spectroscopy, or total internal reflection ellipsometry (SERS). In addition, compared to photometry and reflectometry, luminescence is more sensitive. It is mainly because luminescence is not affected by excitation light interference during the detection process [132]. Raman signals that are normally weak can increase by multiple orders of magnitude using SERS, aiding in the detection of chemical and biochemical substances [133].

The composition of a reflectometric sensor is simple, consisting of a light source, a filter, and a detector. Among them, the filter was used to select the detection wavelength. Biogenic amines sensing can be read out using a reflectometer and analyzed by using the standard of the International Commission on Illumination (CIE) system [134]. Embedding NIR dyes reactive with biogenic amines into electrospun nanofiber mats to form a reflectometric dipstick sensor and preparing electrospun nanofibers through a straightforward, conventional electrospinning process, which also contains S0378 cyanine dye absorbed at 800 nm [130]. Biogenic amines can undergo a color change by binding with dyes, from green to blue, and dipstick can be used to detect total amine content (TAC). During the experiment, as biogenic amines concentration rose, the blue color gradually deepened. The concentration started from 0.2 mM, and the blue change was most pronounced. Quantitative analysis of biogenic amines revealed that shrimp aged at room temperature were taken as the research object. The solution of biogenic amine was added to a dipstick, and the reflectance of the test paper was measured. Finally, a graph was plotted relative to biogenic amine concentration. The histamine concentration on the 0th, 1st, and 6th day of aging were 7.54 ± 0.96, 12.8 ± 0.8, and 21.7 ± 3.2 µ mol/g, respectively (n = 4).

Combining photometry with CE for indirect detection of biogenic amines [135]. One notable benefit of this approach is that it eliminates the need for derivative processing, saving a lot of time and energy. The experiment indicated that amines can be determined within the range of 0.05–1 µg mL⁻¹, and the recovery rates of several representative biogenic amines are between 90–110%, demonstrating long-term stability and reproducibility.

In the luminescence method, the application of ion covalent organic frameworks (iCOFs) was considered. These represented a novel class of porous material that was made up of ionic and covalent bonds with significant chemical stability, adsorption, and selectivity. A study has designed an iCOF chemo-sensor, which was formed by condensing triamino-guanidine hydrochloride salt (TGH • Cl) and phenanthroline-2,9-dicarbaldehyde (PD) [136]. The iCOF was abbreviated as TGH⁺ • PD. Figure 9 shows its chemical structure and condensation method.

TGH⁺ • PD was easily dispersed in water and served as an electron donor, transferring electrons from phenanthroline to the electron acceptor guanidinium unit, forming intramolecular charge transfer (ICT), which results in a color change (orange). When it bound to the analyte, the fluorescence color changed [136]. The iCOF structure was characterized by a helical fiber morphology [136], which was attributed to the presence of water molecules. They were mainly located near the guanidine unit. In the experiment, the iCOF was treated with heat, and it was found that the helical structure was destroyed. If it came into contact with water molecules again, its morphology could be restored. In order to verify the effectiveness of TGH⁺ • PD in detecting biogenic amines, fresh chicken meat was stored in a sealed beaker at 4 °C. The fluorescence intensity was not significant within two days, mainly due to the low amounts of biogenic amines produced under these conditions. Then, the sealed beaker was transferred to room temperature, and the fluorescence intensity significantly increased, indicating that the iCOF could effectively detect biogenic amines and act as an observing signal for spoilage. In addition, in order to investigate the practicality and convenience of TGH⁺ • PD, its aqueous dispersion was applied to filter paper to prepare a test strip, which was then placed on top of spoiled chicken. As the amine vapor evaporated, the color of the detection strip changed from orange to yellow-green. Interestingly, if the yellow-green test strip was moved to fresh air, its color would change back to the initial orange. This experiment successfully validated the practicality of TGH⁺ • PD and discovered a convenient, easy, and low-cost method for detecting biogenic amines.

5. Conclusions and Future Perspective

Aquatic products are rich in fat and protein. Under suitable conditions, microorganisms can grow and reproduce, inducing the generation of substantial quantities of biogenic amines, leading to the spoilage of aquatic products, and excessive human intake can also cause harm. Therefore, it is crucial to determine the types of biogenic amines and their concentrations in aquatic products. Microbiological and molecular biology methods can be used for the initial detection of biogenic amines due to their inability to be quantitatively analyzed. Chromatography such as HPLC, LC, and GC is widely used and the most common method, but sometimes requires high equipment and operators. Sensors, especially chemo-sensors, are widely developed for their speed, simplicity, and cost-effectiveness. Although nanomaterials have good detection performance for chemical sensors, they have certain specificity for different biogenic amines due to their different aggregation behaviors. The color change caused by the pH sensor through acid–base reaction makes the detection results easy to observe, but this method alone cannot be quantitatively analyzed and has low sensitivity. Similarly, fluorescence analysis has low sensitivity and cannot qualitatively and quantitatively detect total biogenic amines in aquatic products. Therefore, new technologies such as fluorescent probes have been developed to improve these drawbacks. This review summarized various detection methods for biogenic amines, all of which have certain drawbacks that need improvement. This review provides theoretical support for more efficient detection of biogenic amines in the future and making contributions to preserving human health and making sure aquatic products are safe to consume.