Analytical Methods for Detection and Quantification of Neurotransmitters: History
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Contributor:
Bruno P. Guiard
,
Guillaume Gotti

Recognized for its speed and selectivity, high-precision liquid chromatography with an electrochemical detector (HPLC-ECD) enables direct analysis of intracerebral microdialysis samples without complex derivatization. Various chromatographic methods, including reverse phase (RP), are explored for neurotransmitters (NTs) and metabolites separation. 

  • HPLC
  • electrochemical detection
  • monoamine
  • neurotransmitters
  • serotoninergic system
  • dopaminergic system

1. Introduction

Monoamine neurotransmitters (NTs) are a class of NTs that include brain chemicals involved in the transmission of signals between nerve cells, or neurons. The two main types of monoamine NTs are catecholamines and indolamines: catecholamines include dopamine (DA), norepinephrine (NE), and epinephrine (E) and indolamines include serotonin (5-hydroxytryptamine or 5-HT).
These monoamine NTs play a crucial role in the regulation of various physiological and behavioral processes, such as the regulation of mood, sleep, appetite, reward, attention, and stress. Imbalances in the functioning of monoamine NTs are associated with various neurological and psychiatric disorders.

2. Analytical Methods for Detection and Quantification of NTs and Metabolites

The analysis methods have been developed for the detection and quantification of NTs in vivo to understand specific neurotransmission dysfunctions in neurodegenerative diseases or in psychiatric disorders.

2.1. Gas Chromatography and Capillary Electrophoresis

Gas chromatography (GC) [1][2] and capillary electrophoresis (CE) [3][4] are analytical techniques used in these research areas. However, they have several drawbacks: GC requires the use of compound derivatization to make them more volatile [5], and CE is a limited technique for the analysis of complex mixtures. HPLC, on the other hand, allows for the analysis of biological samples from microdialysis without the need for chemical derivatization or extraction steps.

2.2. HPLC

Since the late 1980s, research teams led by Donzanti et al. [6], Peinado et al. [7], and Rogers et al. [8] have focused their studies on the detection of amino acid neurotransmitters, particularly γ-aminobutyric acid (GABA), achieving a sensitivity of about 0.1 nM. HPLC analysis of NTs is characterized by its speed and selectivity. Typically, a reverse-phase (RP) system is used to separate NTs due to their hydrophobic nature. For instance, Bidel et al. developed an HPLC method for the separation of monoamines and their metabolites. They achieved a total elution time of about 12 min, a minimum resolution between each peak of 2.2, and a number of theoretical plates (N) ranging from 2900 to 3800 [9]. These values are largely sufficient to validate the use of HPLC.
By way of comparison, Reinhoud et al. developed a UHPLC method similar conditions under reverse phase conditions, enabling the separation of NTs in a 12 min run time elution. The columns of UHPLC have smaller particle sizes. Consequently, chromatographic peaks will be finer and better defined, allowing for improved separation of compounds. Moreover, the number of theoretical plates in this study has been estimated to be close to 200,000 [10].
More recently, hydrophilic interaction liquid chromatography (HILIC) columns have been employed [11][12]. These columns offer reduced system pressure, allowing for enhanced flow rates and shorter analysis times. For example, in the study by Zhou et al., the use of a low-granularity column (1.7 µm) combined with a flow rate of 0.4 mL min−1 is employed. These experimental conditions result in very short analysis times, on the order of 4 min. It is noteworthy that the Multiple Reaction Monitoring (MRM) mode of the mass spectrometer enhances the selectivity of the measurements [13].
The utilization of HILIC column necessitates coupling with mass spectrometry because of its incompatibility with the salts used with the electrochemical detection.

2.3. Detection of NTs and Their Metabolites

Various types of detectors can be employed, including fluorescence detectors (FLD) [14][15][16], mass spectrometry (MS) [17][18][19], sensors and biosensors [20][21][22] or electrochemical detector (ECD). ECD holds an advantage over MS detectors due to its lower operating cost and easy maintenance. For instance, weekly polishing of a glassy carbon (GC) working electrode with alumina powder is adequate to maintaining a reflective surface, thereby enhancing result repeatability and reproducibility.
ECD has also been extensively utilized for the detection and quantification of NTs and their metabolites [23][24][25][26]. It proves to be a straightforward and sensitive method for quantifying small amounts of NTs. One of its notable benefits is its simplicity and minimal maintenance.
Several types of electrochemical detectors exist, including coulometric and amperometric detectors. The principle of the coulometric detector lies in the measurement of the current charge produced during electrolysis at a constant potential. Compounds are then oxidized or reduced almost entirely. Coulometric detectors are less sensitive to variations in flow rate and temperature than amperometric detectors. However, electrodes are easily contaminated due to their large electrolysis surface area. The measurement of the charge during the electrochemical reaction is based on Faraday’s law (Equation (1)).
Q=n F NO      (1)
with Q the charge (C or A s), n the number of electrons exchanges during the electrochemical detection, F the Faraday’s constant (96,485 C mol−1) and NO the number of moles of the O compound.
Amperometric detection generally provides high sensitivity and the response remains linear over a wide range of concentrations. For these reasons, they are more widespread than coulometric detectors. Compared to coulometric detection, electrolysis consumes only about 10% of the analyte. The value of the measured current in an amperometric detector depends on the geometry of the electrode used (Table 1).
Table 1. Limiting current equation as a function of geometry electrode used during the amperometric detection [27].
Electrode Geometry Limiting Current Equation
Tubular i=1.61nFCO(DA/r)2/3ν1/3
Planar, parallel flow in channel i=1.47nFCO(DA/b)2/3ν1/3
Planar, perpendicular flow i=0.903nFCOD2/3ν−1/6A3/4U1/2
Wall jet i=0.898nFCOD2/3ν−5/12a−1/2A3/8ν3/4
With: i the intensity (A), CO concentration of the O compound (mol cm−3), D the diffusion coefficient (cm2 s−1), A the electrode area (cm2), r radius of the tubular electrode (cm), ν average volume flow rate (cm3 s−1), b channel height (cm), U flow velocity (cm s−1) and a diameter of jet intel (cm).
Regardless of the detector used, the number of electrons exchanged determines the measured current during the analysis. In case of detecting 5-HT, the number of electrons exchanges is 2 during the oxidation.
For electroactive compounds, charge can be correlated with the moles of the considered compound, extending to concentration. It is crucial to emphasize that the number of electrons exchanged in the electrochemical reaction is contingent on the applied potential. If the overvoltage is insufficient, then the electrochemical reaction remains incomplete.
ECD has some limitations: this detector is not universal and compounds must be electroactive to be detectable. In the same domain, GABA, a neurotransmitter involved in neurodegenerative diseases [28][29], can be analyzed by HPLC-ECD. However, GABA is not electroactive and requires chemical derivatization. In the Panrod et al. study, two derivatization pathway involving aldehydes moieties have been employed to be able to detect GABA [30]. Therefore, the development of a single analytical method for all NTs with an electrochemical detector appears to be challenging in light of the mentioned limitations.
The two most frequently employed working electrode materials are GC and boron-doped diamond (BDD). These materials showcase diverse physicochemical characteristics: the BDD electrode boasts the largest electrochemical window, facilitating the detection of numerous electroactive compounds. However, as indicated in the study by Zhang et al. in 2016, a high overpotential seems to reduce the peak area of the analytes. The sensitivity of electrode passivation is higher for a BDD electrode compared to a GC electrode [31]. Consequently, it seems that reproducibility is superior with a GC electrode.
The GC electrode exhibits a narrower electrochemical window compared to the BDD electrode. Consequently, the analysis range is restricted, and the oxidation of water impedes the detection of compounds with high oxidation potentials [32]. Analyzing compounds with potentials involving reduction is impossible due to the reduction of dissolved oxygen [33]. Ultimately, the choice between the two electrodes depends on the application when the compounds have relatively low oxidation potentials. Then, it is preferable to use a GC working electrode.
To enhance the sensitivity of NTs detection, two optimizations are considered: firstly, increasing the surface-to-volume ratio of the electrochemical cell, and secondly, using a modified electrode material to enhance its physicochemical characteristics. In the study by Xu et al., the working electrode on GC is modified through an electrochemical reaction with poly(para-aminobenzoic acid) (P-pABA) [34]. With a 0.7 V vs. Ag/AgCl potential detection, the sensitivity of measurement improved from 8.5 nA to 23 nA, 11 nA to 23 nA, 7 nA to 16 nA, 9 nA to 25 nA and 4 nA to 23 nA for 5-HIAA, 5-HT, DA, DOPAC and HVA, respectively. Augmenting sensitivity enhances the quantification of NTs.
In conclusion, the ECD is widely employed for the detection of monoamines due to its user-friendly nature and low maintenance cost. Its sensitivity enables the quantification of very low concentrations of NTs. To expand the capabilities of this detector, it would be possible to develop chemical derivatizations either directly on the compounds or on the electrode surface. These chemical modifications could induce a broader spectrum of applications.

2.4. Limit of Detection and Quantification

By convention, the limit of detection (LOD) and limit of quantification (LOQ) are established at signal-to-noise ratios of 3 and 10, respectively. The linear range (L.R.) denotes the measurement zone where the device-recorded signal is directly proportional to the quantity or concentration of the substance being measured.
Table 2 compiles the various values of LOD, LOQ, and the linear range for the NTs and their metabolites. Additionally, the different experimental conditions have been reported for informational purposes. The studies are ranked based on the particle size of the chromatographic C18 column used, from smallest to largest. The list of presented publications is not exhaustive. Other articles have been published on the use of HPLC-ECD but they did not detail the analytical development and LOD/LOQ of NTs. Those articles were not included in this summary table. For instance, one can cite several recent works by Guo et al. (2023) [35], Lei et al. (2023) [36], and Wang et al. (2022) [37].
According to these studies, the sensitivity of the targeted molecules can approach values close to 10−9 mol L−1 for HPLC system and less, close to 10−11 mol L−1, in UHPLC cases. As mentioned earlier, the use of columns with small particle sizes refines elution peaks and consequently lowers quantification limits. However, using such columns induces high back pressure. These low values facilitate the collection of microdialysis samples in the range of microliter, enabling real-time monitoring of neurotransmitter concentrations.
In electrochemical detection processes, the use of salts becomes crucial to increase conductivity and consequently achieve optimal performance. Typically, the aqueous phase of the mobile phase incorporates essential components, such as chelating compounds (e.g., sodium citrate, EDTA), which play a role in preventing coagulation [38], an anionic surfactant (sodium dodecyl sulfate, octane sulfonic acid) to prevent interference with lipids and enhance the retention of anionic compounds [39], and finally, a buffer (phosphate, citrate).
Most of the time, the pH of the mobile phase is buffered in an acidic environment. The more acidic the eluent, the faster the compounds will elute. Additionally, some compounds are sensitive and degrade more rapidly at basic pH. For instance, this is the case with DA, which oxidizes at a significant rate under basic pH conditions: the half-life at pH 5.6, 7.1, and 7.4 is 13.5 days, 19.7 min, and 4.95 min, respectively [40].
Moreover, the mobile phase, predominantly consisting of the aqueous phase with salts, is often augmented with methanol and/or acetonitrile. This strategic addition enhances the eluent’s apolar characteristics, ensuring a comprehensive and effective electrochemical detection setup.
Table 2. Recent values of separation, detection and quantification of compounds involved in serotonergic system and their application (non-exhaustive list). All values provided have been standardized to the same unit (mol L−1) for the purpose of comparability.
Reference   HPLC-ECD Conditions Application
Reinhoud et al. (2013) [10] Methods and Application C18 column (1.0 × 100 mm, 1.7 µm particles size)
Flow rate = 50 µL min−1
Column temperature = 37 °C
Injection volume = 5 µL
Mobile phase: 100 mM phosphoric acid, 100 mM citric acid, 8 mM KCl, 0.1 mM EDTA and 2.8 mM OSA.
ACN/H2O (8/92; v/v)
pH = 3
Detection: GC working electrode (+0.65 V vs. Ag/AgCl)		 Development of analytical method for the determination of monoamines concentrations and application to a microdialysis in a prefrontal cortex.
Detection (mol L−1)   5-HT 5-HIAA DA DOPAC HVA
LOD 8.3 × 10−11 3.5 × 10−11 4.2 × 10−11 5.0 × 10−11 4.7 × 10−11
Ferry et al. (2014) [41] Methods and Application C18 column (0.32 × 100 mm, 1.9 µm particles size)
Flow rate = 8.5 µL min−1
Column temperature = 40 °C
Injection volume = 1 µL
Mobile phase: 140 mM potassium phosphate, 8 mM KCl, 0.1 mM EDTA, 6 mM OSA.
MeOH/H2O (6/94; v/v)
pH = 5 (adjusted with 10 mM NaOH)
Detection: GC working electrode (+0.45 V vs. Ag/AgCl)		 Development of analytical method for the determination of monoamines concentrations and application to microdialysis in the dorsal hippocampus
Detection (mol L−1)   5-HT DA 3-MT
LOD 1.5 × 10−9 7.5 × 10−10 1.5 × 10−9
LOQ 5.0 × 10−9 2.5 × 10−9 5.0 × 10−9
Schou-Pedersen et al. (2016) [42] Methods and Application C18 column (4.6 × 100 mm, 2.6 µm particles size)
Flow rate = 0.8 mL min−1
Column temperature = 30 °C
Injection volume = 20 µLMobile phase: 70 mM potassium dihydrogen phosphate, 2 mM OSA, 0.1 mM EDTA.
MeOH/H2O (10/90; v/v)
pH = 3.12 (adjusted with 1 M citric acid)
Detection: Porous graphite working electrode
(+0.40 V vs. Pd)		 Development of chromatographic method for the quantification of monoamine NTs from sub-regions of guinea pig brain (intracellular and extracellular).
Detection (mol L−1)   5-HT 5-HIAA DOPAC DA HVA
LOQ 8.8 × 10−9 3.8 × 10−9 3.6 × 10−9 1.0 × 10−8 1.2 × 10−8
L.R. 8.8 × 10−9–1.0 × 10−6 3.8 × 10−9–1.0 × 10−6 3.6 × 10−9–1.0 × 10−6 1.0 × 10−8–7.5 × 10−7 1.2 × 10−8–5.0 × 10−7
Van Dam et al. (2014) [43] Methods and Application C18 column (1.0 × 250 mm, 3.0 µm particles size)
Flow rate = 40 µL min−1
Column temperature = from 30 °C to 36 °C
Injection volume = 50 µL
Mobile phase: 8 mM KCl, 50 mM phosphoric acid, 50 mM citric acid, 0.1 mM EDTA, from 1.8 to 2.2 mM OSA.
MeOH/H2O (from 13/87 to 17/83; v/v)
pH = from 3.0 to 3.6 (adjusted with NaOH)
Detection: GC working electrode (from +0.63 V to +0.67 V vs. Ag/AgCl)		 Development of analytical method for the quantification of biogenic amines and metabolites in human brain tissue.
Detection (mol L−1)   5-HT 5-HIAA DOPAC DA HVA
L.R. 5.3 × 10−10–1.8 × 10−7 2.2 × 10−10–7.7 × 10−8 2.8 × 10−10–1.6 × 10−7 2.7 × 10−10–1.8 × 10−7 5.8 × 10−10–3.2 × 10−7
Pantiya et al. (2024) [44] Methods and Application C18 column (3.0 × 500 mm, 2.6 µm particles size)
Flow rate = 0.5 mL min−1
Column temperature = 25 °C
Injection volume = 25 µLMobile phase: 130 mM sodium phosphate monobasic, 20 mM orthophosphoric acid, 2 mM sodium dodecyl sulfate, 50 µM EDTA. ACN, MeOH, H2O (5/10/95; v/v/v)
pH = 3.2 (adjusted with phosphate buffer)
Detection: GC working electrode (+0.50 V vs. Ag/AgCl)		 Development of analytical method for the quantification of NTs and metabolites in brain mice microdialysates.
Detection (mol L−1)   5-HT 5-HIAA DA HVA
LOD 3.1 × 10−10 5.4 × 10−10 3.7 × 10−10 4.1 × 10−10
LOQ 3.9 × 10−10 5.8 × 10−10 4.2 × 10−10 4.3 × 10−10
Allen et al. (2017) [45] Methods and Application C18 column (3.2 × 150 mm, 3.0 µm particles size)
Flow rate = 0.6 mL min−1
Column temperature = N/A
Injection volume = 40 µLMobile phase: 100 mM sodium acetate, 20 mM citric acid, 0.38 mM sodium octyl sulfate, 0.15 mM EDTA.
ACN/H2O (5/95; v/v)
pH = 3.3 (adjusted with glacial acetic acid)
Detection: Dual working electrode (−0.22 V and +0.375 V)		 Development of analytical method for the quantification of monoamines and metabolites in brain tissue of mice.
Detection (mol L−1)   5-HT 5-HIAA DOPAC DA HVA
LOD 1.7 × 10−9 6.5 × 10−10 7.4 × 10−10 8.2 × 10−10 4.1 × 10−10
LOQ 3.6 × 10−9 1.3 × 10−9 1.5 × 10−9 1.6 × 10−9 1.4 × 10−9
L.R. 3.6 × 10−9–1.7 × 10−4 1.3 × 10−9–7.9 × 10−5 1.5 × 10−9–8.9 × 10−5 1.6 × 10−9–2.0 × 10−4 1.4 × 10−9–8.2 × 10−5
Yardimci et al. (2023) [46] Methods and Application C18 column (4.6 × 250 mm, 5.0 µm particles size)
Flow rate = 1 mL min−1
Column temperature = 36 °C
Injection volume = 20 µL
Mobile phase: 35 mM citric acid, 19 mM sodium citrate, 0.16 mM EDTA, 1.1 mM heptasulfonic acid. Glacial acetic acid/tetrahydrofuran/MeOH/H2O
(0.11/0.3/2.5/97.085; v/v/v/v)
pH = 4.9 (adjusted with 10 M NaOH)
Detection: GC working electrode (+0.50 V vs. Ag/AgCl)		 Analysis in hypothalamic and subcortical nuclei
Detection (mol L−1)   5-HT 5-HIAA DA DOPAC
LOQ 5.7 × 10−7 5.2 × 10−7 6.5 × 10−7 6.0 × 10−7
Du et al. (2018) [47] Methods and Application C18 column (4.6 × 250 mm, 5.0 µm particles size)
Flow rate = 1 mL min−1
Column temperature = 25 °C
Injection volume = 20 µL
Mobile phase: 25 mM sodium citrate, 0.01 mM EDTA.
ACN/H2O (5/95; v/v)
pH = 4.5 (adjusted with 1 M acetic acid)
Detection: BDD working electrode (+0.70 V vs. Ag/AgCl)		 Analytical method development
Detection (mol L−1)   5-HT 5-HIAA
LOD 2.1 × 10−8 1.6 × 10−8
LOQ 2.8 × 10−8 4.2 × 10−8
L.R. 2.8 × 10−8–1.1 × 10−6 2.6 × 10−8–2.6 × 10−6
Zhang et al. (2016) [48] Methods and Application C18 column (4.6 × 250 mm, 5.0 µm particles size)
Flow rate = 1 mL min−1
Column temperature = 25 °C
Injection volume = 20 µL
Mobile phase: 25 mM sodium citrate, 0.01 mM EDTA.
ACN/H2O (5/95; v/v)
pH = 4.5 (adjusted with 1 M acetic acid)
Detection: BDD working electrode (+0.70 V vs. Ag/AgCl)		 Determination of the concentrations of monoamines NTs in rat cortex and hippocampus tissues.
Detection (mol L−1)   5-HT 5-HIAA DA DOPAC 3-MT HVA
LOD 2.3 × 10−8 1.1 × 10−8 2.6 × 10−8 1.2 × 10−8 3.6 × 10−8 2.7 × 10−8
LOQ 8.5 × 10−8 3.1 × 10−8 9.8 × 10−8 4.8 × 10−8 1.2 × 10−7 8.2 × 10−8
L.R. 8.5 × 10−8–1.4 × 10−6 3.1 × 10−8–7.9 × 10−7 9.8 × 10−8–2.3 × 10−6 6.0 × 10−8–3.0 × 10−6 1.2 × 10−7–1.8 × 10−6 8.2 × 10−8–1.4 × 10−6
Jiang et al. (2015) [49] Methods and Application C18 column (4.6 × 250 mm, 5.0 µm particles size)
Flow rate = 1 mL min−1
Column temperature = 30 °C
Injection volume = 10 µL
Mobile phase: 50 mM potassium dihydrogen phosphate, 0.1 mM octane sulfonic acid.
MeOH/H2O (5/95; v/v)
pH = N/A
Detection: GC working electrode (+0.70 V vs. Ag/AgCl)		 Development of the analytical method for monoamines NTs in human urine.
Detection (mol L−1)   5-HT DA
LOD 6.1 × 10−8 3.9 × 10−8
Lokhande et al. (2022) [50] Methods and Application C18 column (4.6 × 250 mm, 5.0 µm particles size)
Flow rate = 1.3 mL min−1
Column temperature = 35 °C
Injection volume = 20 µL
Mobile phase: 50 mM potassium dihydrogen phosphate, 0.99 mM SOS and 53 µM EDTA.
MeOH/H2O (12/88; v/v)
pH = 2.5 (adjusted with 85% phosphoric acid)
Detection: BDD working electrode (+0.70 V vs. Ag/AgCl)		 Development of the analytical method for metabolites quantification in human CSF.
Detection (mol L−1)   5-HIAA HVA
LOQ 6.5 × 10−8 6.9 × 10−8
L.R. 6.5 × 10−8–2.6 × 10−6 6.9 × 10−8–2.7 × 10−6
Abreviations: N/A: not available, LOD: limit of detection, LOQ: limit of quantification, L.R.: linear range, EDTA: ethylendiaminetetraacetic acid, OSA: octane sulfonic acid, SOS: sodium octane sulfonate, ACN: acetonitrile, MeOH: methanol.

This entry is adapted from the peer-reviewed paper 10.3390/molecules29020496

References

  1. Zhang, P.; Wang, B.; Sun, Y.; Gao, J.; Lian, K. Analysis of 5-Hydroxytryptamine and Its Related Indoles in Cerebrospinal Fluid of Leukemic Children by Gas Chromatography-Mass Spectrometry. J. Lab. Med. 2020, 44, 41–45.
  2. Shi, H.; Wang, B.; Niu, L.; Cao, M.; Kang, W.; Lian, K.; Zhang, P. Trace Level Determination of 5-Hydroxytryptamine and Its Related Indoles in Amniotic Fluid by Gas Chromatography–Mass Spectrometry. J. Pharm. Biomed. Anal. 2017, 143, 176–182.
  3. Tsai, H.; Whang, C. Capillary Electrophoresis of Monoamines and Catechol with Indirect Chemiluminescence Detection. Electrophoresis 1999, 20, 2533–2538.
  4. Benturquia, N.; Couderc, F.; Sauvinet, V.; Orset, C.; Parrot, S.; Bayle, C.; Renaud, B.; Denoroy, L. Analysis of Serotonin in Brain Microdialysates Using Capillary Electrophoresis and Native Laser-Induced Fluorescence Detection. Electrophoresis 2005, 26, 1071–1079.
  5. Hattox, S.E.; Murphy, R.C. Mass Spectrometry and Gas Chromatography of Trimethylsilyl Derivatives of Catecholamine Related Molecules. Biol. Mass Spectrom. 1978, 5, 338–345.
  6. Donzanti, B.A.; Yamamoto, B.K. An Improved and Rapid HPLC-EC Method for the Isocratic Separation of Amino Acid Neurotransmitters from Brain Tissue and Microdialysis Perfusates. Life Sci. 1988, 43, 913–922.
  7. Peinado, J.M.; McManus, K.T.; Myers, R.D. Rapid Method for Micro-Analysis of Endogenous Amino Acid Neurotransmitters in Brain Perfusates in the Rat by Isocratic HPLC-EC. J. Neurosci. Methods 1986, 18, 269–276.
  8. Rogers, K.L.; Philibert, R.A.; Allen, A.J.; Molitor, J.; Wilson, E.J.; Dutton, G.R. HPLC Analysis of Putative Amino Acid Neurotransmitters Released from Primary Cerebellar Cultures. J. Neurosci. Methods 1987, 22, 173–179.
  9. Bidel, F.; Corvaisier, S.; Jozet-Alves, C.; Pottier, I.; Dauphin, F.; Naud, N.; Bellanger, C. An HPLC-ECD Method for Monoamines and Metabolites Quantification in Cuttlefish (Cephalopod) Brain Tissue: Biogenic Monoamines and Metabolites in Cuttlefish (Cephalopod) Brain. Biomed. Chromatogr. 2016, 30, 1175–1183.
  10. Reinhoud, N.J.; Brouwer, H.-J.; Van Heerwaarden, L.M.; Korte-Bouws, G.A.H. Analysis of Glutamate, GABA, Noradrenaline, Dopamine, Serotonin, and Metabolites Using Microbore UHPLC with Electrochemical Detection. ACS Chem. Neurosci. 2013, 4, 888–894.
  11. Tufi, S.; Lamoree, M.; De Boer, J.; Leonards, P. Simultaneous Analysis of Multiple Neurotransmitters by Hydrophilic Interaction Liquid Chromatography Coupled to Tandem Mass Spectrometry. J. Chromatogr. A 2015, 1395, 79–87.
  12. Chirita, R.-I.; West, C.; Finaru, A.-L.; Elfakir, C. Approach to Hydrophilic Interaction Chromatography Column Selection: Application to Neurotransmitters Analysis. J. Chromatogr. A 2010, 1217, 3091–3104.
  13. Zhou, G.-S.; Yuan, Y.-C.; Yin, Y.; Tang, Y.-P.; Xu, R.-J.; Liu, Y.; Chen, P.-D.; Yin, L.; Duan, J.-A. Hydrophilic Interaction Chromatography Combined with Ultrasound-Assisted Ionic Liquid Dispersive Liquid–Liquid Microextraction for Determination of Underivatized Neurotransmitters in Dementia Patients’ Urine Samples. Anal. Chim. Acta 2020, 1107, 74–84.
  14. Boulghobra, A.; Bonose, M.; Billault, I.; Pallandre, A. A Rapid and Sensitive Method for the Quantification of Dopamine and Serotonin Metabolites in Cerebrospinal Fluid Based on UHPLC with Fluorescence Detection. J. Chromatogr. B 2022, 1200, 123264.
  15. De Benedetto, G.E.; Fico, D.; Pennetta, A.; Malitesta, C.; Nicolardi, G.; Lofrumento, D.D.; De Nuccio, F.; La Pesa, V. A Rapid and Simple Method for the Determination of 3,4-Dihydroxyphenylacetic Acid, Norepinephrine, Dopamine, and Serotonin in Mouse Brain Homogenate by HPLC with Fluorimetric Detection. J. Pharm. Biomed. Anal. 2014, 98, 266–270.
  16. Zhao, H.-X.; Mu, H.; Bai, Y.-H.; Yu, H.; Hu, Y.-M. A Rapid Method for the Determination of Dopamine in Porcine Muscle by Pre-Column Derivatization and HPLC with Fluorescence Detection. J. Pharm. Anal. 2011, 1, 208–212.
  17. Carrera, V.; Sabater, E.; Vilanova, E.; Sogorb, M.A. A Simple and Rapid HPLC–MS Method for the Simultaneous Determination of Epinephrine, Norepinephrine, Dopamine and 5-Hydroxytryptamine: Application to the Secretion of Bovine Chromaffin Cell Cultures. J. Chromatogr. B 2007, 847, 88–94.
  18. Xu, N.; Qiu, C.; Wang, W.; Wang, Y.; Chai, C.; Yan, Y.; Zhu, D. HPLC/MS/MS for Quantification of Two Types of Neurotransmitters in Rat Brain and Application: Myocardial Ischemia and Protection of Sheng-Mai-San. J. Pharm. Biomed. Anal. 2011, 55, 101–108.
  19. Kovac, A.; Somikova, Z.; Zilka, N.; Novak, M. Liquid Chromatography–Tandem Mass Spectrometry Method for Determination of Panel of Neurotransmitters in Cerebrospinal Fluid from the Rat Model for Tauopathy. Talanta 2014, 119, 284–290.
  20. Shao, Z.; Chang, Y.; Venton, B.J. Carbon Microelectrodes with Customized Shapes for Neurotransmitter Detection: A Review. Anal. Chim. Acta 2022, 1223, 340165.
  21. Polo, E.; Kruss, S. Nanosensors for Neurotransmitters. Anal. Bioanal. Chem. 2016, 408, 2727–2741.
  22. Banerjee, S.; McCracken, S.; Hossain, M.F.; Slaughter, G. Electrochemical Detection of Neurotransmitters. Biosensors 2020, 10, 101.
  23. Dicgory, G.L.; Buckett, W.R. An Automated Method to Measure Monoamines and Metabolites Using Elevated Temperature Reversed Phase HPLC with Electrochemical Detection Application to Striatal Dopamine and Hippocampal Serotonin Turnover. J. Pharmacol. Methods 1984, 11, 207–217.
  24. Cannazza, G.; Di Stefano, A.; Mosciatti, B.; Braghiroli, D.; Baraldi, M.; Pinnen, F.; Sozio, P.; Benatti, C.; Parenti, C. Detection of Levodopa, Dopamine and Its Metabolites in Rat Striatum Dialysates Following Peripheral Administration of l-DOPA Prodrugs by Mean of HPLC–EC. J. Pharm. Biomed. Anal. 2005, 36, 1079–1084.
  25. Birch, P.J.; Fillenz, M. Measurement of Noradrenaline Synthesis in Rat Hippocampal Synaptosomes Using HPLC with ECD. J. Neurosci. Methods 1985, 13, 231–238.
  26. Saito, H.; Murai, S.; Abe, E.; Masuda, Y.; Itoh, T. Rapid and Simultaneous Assay of Monoamine Neurotransmitters and Their Metabolites in Discrete Brain Areas of Mice by HPLC with Coulometric Detection. Pharmacol. Biochem. Behav. 1992, 42, 351–356.
  27. Bard, A.J.; Faulkner, L.R. Electrochemical Methods, Fundamentals and Applications; John Wiley & Sons Inc.: New York, NY, USA, 2001; ISBN 0-471-04372-9.
  28. Błaszczyk, J.W. Parkinson’s Disease and Neurodegeneration: GABA-Collapse Hypothesis. Front. Neurosci. 2016, 10, 239.
  29. Nägga, K.; Bogdanovic, N.; Marcusson, J. GABA Transporters (GAT-1) in Alzheimer’s Disease. J. Neural Transm. 1999, 106, 1141–1149.
  30. Panrod, K.; Tansirikongkol, A.; Panapisal, V. Comparison of Validated High-Performance Liquid Chromatography Methods Using Two Derivatizing Agents for Gamma-Aminobutyric Acid Quantification. Thai J. Pharm. Sci. 2016, 40, 203–208.
  31. Narmadha, M.; Noel, M.; Suryanarayanan, V. Relative Deactivation of Boron-Doped Diamond (BDD) and Glassy Carbon (GC) Electrodes in Different Electrolyte Media Containing Substituted Phenols—Voltammetric and Surface Morphologic Studies. J. Electroanal. Chem. 2011, 655, 103–110.
  32. Gotti, G.; Evrard, D.; Gros, P. Simultaneous Electrochemical Detection of Oxygen (O2) and Hydrogen Peroxide (H2O2) in Neutral Media. Int. J. Electrochem. Sci. 2023, 18, 100262.
  33. Gotti, G.; Fajerwerg, K.; Evrard, D.; Gros, P. Kinetics of Dioxygen Reduction on Gold and Glassy Carbon Electrodes in Neutral Media. Int. J. Electrochem. Sci. 2013, 8, 12643–12657.
  34. Xu, F.; Gao, M.; Shi, G.; Wang, L.; Zhang, W.; Xue, J.; Jin, L.; Jin, J. Simultaneous Detection of Monoamines in Rat Striatal Microdialysate at Poly(Para-Aminobenzoic Acid) Modified Electrode by High-Performance Liquid Chromatography. Anal. Chim. Acta 2001, 439, 239–246.
  35. Guo, Y.-X.; Xia, C.-Y.; Yan, Y.; Han, Y.; Shi, R.; He, J.; Wang, Y.-M.; Wang, Z.-X.; Zhang, W.-K.; Xu, J.-K. Loganin Improves Chronic Unpredictable Mild Stress-Induced Depressive-like Behaviors and Neurochemical Dysfunction. J. Ethnopharmacol. 2023, 308, 116288.
  36. Lei, C.; Chen, H.; Chen, K. Effects of Bone Marrow Mesenchymal Stem Cells on Myelin Repair and Emotional Changes of a Cuprizone-Induced Demyelination Model. J. Integr. Neurosci. 2023, 22, 40.
  37. Wang, Z.-X.; Lian, W.-W.; He, J.; He, X.-L.; Wang, Y.-M.; Pan, C.-H.; Li, M.; Zhang, W.-K.; Liu, L.-Q.; Xu, J.-K. Cornuside Ameliorates Cognitive Impairments in Scopolamine Induced AD Mice: Involvement of Neurotransmitter and Oxidative Stress. J. Ethnopharmacol. 2022, 293, 115252.
  38. Kalantary, R.R.; Moradi, M.; Pirsaheb, M.; Esrafili, A.; Jafari, A.J.; Gholami, M.; Vasseghian, Y.; Antolini, E.; Dragoi, E.-N. Enhanced Photocatalytic Inactivation of E. Coli by Natural Pyrite in Presence of Citrate and EDTA as Effective Chelating Agents: Experimental Evaluation and Kinetic and ANN Models. J. Environ. Chem. Eng. 2019, 7, 102906.
  39. Broch, S.C.; Celia García Alvarez-Coque, M.; Broch, S.C.; Esteve-Romero, J.S. Liquid Chromatographic Determination of Some Thiazide Diuretics in Pharmaceuticals with a Sodium Dodecyl Sulfate Mobile Phase. Analyst 1998, 123, 301–306.
  40. Umek, N.; Geršak, B.; Vintar, N.; Šoštarič, M.; Mavri, J. Dopamine Autoxidation Is Controlled by Acidic pH. Front. Mol. Neurosci. 2018, 11, 467.
  41. Ferry, B.; Gifu, E.-P.; Sandu, I.; Denoroy, L.; Parrot, S. Analysis of Microdialysate Monoamines, Including Noradrenaline, Dopamine and Serotonin, Using Capillary Ultra-High Performance Liquid Chromatography and Electrochemical Detection. J. Chromatogr. B 2014, 951–952, 52–57.
  42. Schou-Pedersen, A.M.V.; Hansen, S.N.; Tveden-Nyborg, P.; Lykkesfeldt, J. Simultaneous Quantification of Monoamine Neurotransmitters and Their Biogenic Metabolites Intracellularly and Extracellularly in Primary Neuronal Cell Cultures and in Sub-Regions of Guinea Pig Brain. J. Chromatogr. B 2016, 1028, 222–230.
  43. Van Dam, D.; Vermeiren, Y.; Aerts, T.; De Deyn, P.P. Novel and Sensitive Reversed-Phase High-Pressure Liquid Chromatography Method with Electrochemical Detection for the Simultaneous and Fast Determination of Eight Biogenic Amines and Metabolites in Human Brain Tissue. J. Chromatogr. A 2014, 1353, 28–39.
  44. Pantiya, P.; Guiard, B.P.; Gotti, G. Sensitive and Fast Detection of Monoamines and Their Metabolites by High-Performance Liquid Chromatography Coupled with an Electrochemical Detector (HPLC-ECD) under Isocratic Conditions. Application to Intracerebral Microdialysis in Mice Treated by Fluoxetine and Atomoxetine. Chromatographia 2024, in press.
  45. Allen, S.A.; Rednour, S.; Shepard, S.; Pond, B.B. A Simple and Sensitive High-performance Liquid Chromatography–Electrochemical Detection Assay for the Quantitative Determination of Monoamines and Respective Metabolites in Six Discrete Brain Regions of Mice. Biomed. Chromatogr. 2017, 31, e3998.
  46. Yardimci, A.; Ertugrul, N.U.; Ozgen, A.; Ozbeg, G.; Ozdede, M.R.; Ercan, E.C.; Canpolat, S. Effects of Chronic Irisin Treatment on Brain Monoamine Levels in the Hypothalamic and Subcortical Nuclei of Adult Male and Female Rats: An HPLC-ECD Study. Neurosci. Lett. 2023, 806, 137245.
  47. Du, T.; Cui, T.; Qiu, H.; Wang, N.; Huang, D.; Jiang, X. Simultaneous Determination of Tryptophan, Kynurenine, Kynurenic Acid and Two Monoamines in Rat Plasma by HPLC-ECD/DAD. J. Pharm. Biomed. Anal. 2018, 158, 8–14.
  48. Zhang, L.; Yang, J.; Luo, Y.; Shang, J.; Jiang, X. Simultaneous Determination of Eleven Compounds Related to Metabolism of Bioamines in Rat Cortex and Hippocampus by HPLC-ECD with Boron-Doped Diamond Working Electrode. J. Pharm. Biomed. Anal. 2016, 118, 41–51.
  49. Jiang, L.; Chen, Y.; Chen, Y.; Ma, M.; Tan, Y.; Tang, H.; Chen, B. Determination of Monoamine Neurotransmitters in Human Urine by Carrier-Mediated Liquid-Phase Microextraction Based on Solidification of Stripping Phase. Talanta 2015, 144, 356–362.
  50. Lokhande, R.V.; Bhagure, G.R.; Dherai, A.J.; Naik, P.R.; Udani, V.P.; Desai, N.A.; Ashavaid, T.F. Analytical Method Validation for Estimation of Neurotransmitters (Biogenic Monoamines) from Cerebrospinal Fluid Using High Performance Liquid Chromatography. Ind. J. Clin. Biochem. 2022, 37, 85–92.
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