In-situ growth of covalent organic framework on stainless steel needles as solid-phase microextraction probe coupled with electrospray ionization mass spectrometry for rapid and sensitive determination of tricyclic antidepressants in biosamples.

Tricyclic antidepressants (TCAs) including amitriptyline (AT), doxepin (DOX) and nortriptyline (NT) are the first-line drugs for the clinical treatment of depression; however, monitoring TCA concentrations in biological fluids and tissues is necessary to improve therapeutic effect and determine the cause of death in patients. It is of great significance to develop a rapid and sensitive method for real-time monitoring of TCAs in various biosamples. In this work, we fabricated a novel covalent organic framework (COF) based solid-phase microextraction (SPME) probe by an in-situ step-by-step strategy, which was obtained by sequentially modifying 1,3,5-tri (4-aminophenyl) benzene (TPB) and 2, 5-divinylbenzaldehyde (DVA) on the surface of polydopamine layer. The TPB-DVA-COF-SPME probe possessed high specific surface area (1244 m2·g - 1), regular pores (3.23 nm), good hydrophobicity and stability, resulting in efficient enrichment for TCAs. Furthermore, the combination of TPB-DVA-COF-SPME probe and ambient electrospray ionization mass spectrometry system (ESI/MS) was firstly proposed for rapid and sensitive determination of TCAs in biosamples. As a result, the developed method exhibited low limits of detection (LODs) (0.1-0.5 µg∙L - 1), high enrichment factors (39-218), and low relative standard deviations (RSDs) for one probe (1.2-3.8%) and probe-to-probe (2.0-3.7%). Benefiting from these outstanding performance, TPB-DVA-COF-SPME probe was further successfully applied to biosamples (i.e., serum, liver, kidney, and brain) with excellent reusability, indicating the promising applicability of the TPB-DVA-COF-SPME-ESI/MS as a powerful tool for drug monitoring.

On-Chip Electromembrane Surrounded Solid Phase Microextraction for Determination of Tricyclic Antidepressants from Biological Fluids Using Poly(3,4-ethylenedioxythiophene)-Graphene Oxide Nanocomposite as a Fiber Coating.

In the present study, on-chip electromembrane surrounded solid phase microextraction (EM-SPME) was employed in the determination of tricyclic antidepressants (TCAs), including amitriptyline, nortriptyline, imipramine, desipramine, maprotiline, and sertraline, from various biological fluids. In this regard, poly(3,4-ethylenedioxythiophene)-graphene oxide (PEDOT-GO) was electrodeposited on an SPME fiber as a conductive coating, then the fiber played the acceptor-electrode role during the extraction. Thus, the immigration of the analytes under the influence of an electric field and their absorption onto the fiber coating were accomplished simultaneously. Under the optimized conditions, the limits of detection for the target analytes were acquired in the range of 0.005-0.025 µg L-1 using gas chromatography-mass spectrometry. The linearity of the method was 0.010-500 µg L-1 for the imipramine and sertraline, 0.025-500 µg L-1 for the amitriptyline, nortriptyline, and desipramine, and 1.000-250 µg L-1 for the maprotiline (R2 ≥ 0.9984). Moreover, this method provided suitable precision and fiber-to-fiber reproducibility, with RSDs ≤ 8.4%. The applicability of the proposed setup was eventually investigated for extraction of the drugs from human bone marrow aspirate, urine, plasma, and well water samples, in which satisfactory relative recoveries, from 93-105%, were obtained.

Investigation of the performance of cross-linked poly(acrylic acid) and poly(methacrylic acid) as efficient adsorbents in SPE columns for simultaneous preconcentration of tricyclic antidepressants in water samples.

A solid phase extraction-based (SPE) procedure for simultaneous preconcentration of five tricyclic antidepressants (TCAs), amitriptyline hydrochloride (AMT), nortriptyline hydrochloride (NOR), doxepin hydrochloride (DOX), imipramine hydrochloride (IMI), and clomipramine hydrochloride (CLO) from water samples with determination by HPLC-DAD is proposed. Polymers were characterized by FT-IR, SEM, and thermogravimetric analysis. SPE-based methods were carried out by the preconcentration of 320.0 mL of TCAs at pH 7.0 (buffered with 0.01 mol L-1 phosphate buffer) through 70.0 mg of adsorbent packed into a SPE cartridge, followed by elution with 1.0 mL of ACN : MeOH : acetic acid solution (45 : 45 : 10% v/v). Higher preconcentration factors were obtained ranging from 117.9 to 372.2 and 207.1 to 396.1 by using poly(MAA-co-EGDMA) and poly(AA-co-EGDMA), respectively, yielding lower limits of detection (0.03 to 0.12 µg L-1) and (0.03 to 0.15 µg L-1). These outcomes show satisfactory detectability of SPE-based methods, with slightly better performance using poly(MAA-co-EGDMA). On the other hand, poly(AA-co-EGDMA) was able to preconcentrate TCAs in the presence of humic acid (7.0 mg L-1) without interference. The precision of methods assessed as RSD (%) was very similar, ranging from 1.7% to 16.3% for poly(MAA-co-EGDMA) and 1.7% to 13.4% for poly(AA-co-EGDMA). SPE cartridges packed with the polymers showed high reusability (52 cycles of preconcentration and elution) without losing adsorption efficiency. The methods were applied to determine TCAs in tap, lake, and stream water samples and the accuracy was attested by addition and recovery tests (86.7-116.0%), with determined nortriptyline ranging from 0.48 to 0.52 µg L-1 in lake water samples.

Recent Advances in the HPLC Analysis of Tricyclic Antidepressants in Bio-Samples.

Tricyclic Antidepressants (TCAs) are a group of the main category of antidepressant drugs, which are commonly prescribed to treat major depressive disorder. Determination of TCA drugs is very important for clinical and forensic toxicology, especially for therapeutic drug monitoring in various biofluids. High Performance Liquid Chromatography (HPLC) is a well-established technique for this purpose. A lot of progress has been made in this field since the past 10 years. Novel extraction techniques, and novel materials for sample preparation, novel columns and novel applications of analysis of various biofluids for the determination of TCAs in combination with other drugs are some typical examples. Moreover, advances have been performed in terms of Green Analytical Chemistry principles. Herein, we aim to discuss the developed HPLC methods that were reported in the literature for the time span of 2008-2018.

Simple and green synthesis of carbon dots (CDs) from valerian root and application of modified mesoporous boehmite (AlOOH) with CDs as a fluorescence probe for determination of imipramine.

A novel, sensitive, rapid, and simple fluorescent probe has been developed based on green-synthesized carbon dots (CDs). In this work, CDs have been synthesized from valerian root by hydrothermal method. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) results confirm the formation of CDs with sizes of less than 10 nm. Fluorescence quenching of CDs was due to the aggregation of the negative charges of CDs with the positive charge of imipramine (IMI) and was then used as the signal for determination of IMI. In addition, the cytotoxicity of CDs was determined using the MTT assay. The probe responses under optimum conditions were linear in the range of 1.0-200.0 ng mL-1 with a limit of detection of 0.6 ng mL-1. Afterwards, mesoporous boehmite (MB) was modified with synthesized CDs (CDs/MB). TEM images confirmed MB modification with CDs. In this case, the variations in the fluorescence signal for different concentrations of IMI increased leading to the higher sensitivity for IMI detection. The limit of detection and linear range for determination of IMI with CDs/MB were obtained as 0.2 and 0.5-200.0 ng mL-1, respectively. To evaluate the fluorescent probe, IMI was measured in real samples. Graphical abstract.

Magnetic framework composite as sorbent for magnetic solid phase extraction coupled with high performance liquid chromatography for simultaneous extraction and determination of tricyclic antidepressants.

In this study, magnetic framework composites (MFCs) (Fe3O4@TMU-10) microspheres were successfully fabricated and applied as an effective sorbent for preconcentration of the two model tricyclic antidepressants (TCAs) amitriptyline and imipramine from biological samples. MFCs were fabricated by a step-by-step assembly, novel, simple and efficient strategy. The shell thickness of the Metal-organic frameworks (MOFs) could also be easily controlled by tuning the number of assembly cycles. By coupling magnetic solid-phase extraction (MSPE) with high-performance liquid chromatography with UV detector (HPLC-UV), a simple, reliable, fast, sensitive and cost-effective method for simultaneous determination of TCAs was developed. Under optimal conditions, the preconcentration factors and relative recoveries of the studied compounds were obtained in the range of 43-50 and 90.5-99.0% respectively. The calibration curves were obtained in the range of 5-800 µg L-1 with reasonable linearity (R2 > 0.9904) and the limits of detection (LODs) ranged between 2 and 4 µg L-1 (based on S/N = 3). The relative standard deviations of intra- and inter-day tests ranged from 3.1 to 4.6% and from 4.3 to 5.2%, respectively. The results demonstrate that Fe3O4@TMU-10 core-shell magnetic microspheres combine advantages of MOFs and magnetic nanoparticles, and are the promising sorbents for rapid and efficient extraction of target analytes from urine and plasma complex biological samples.

Extraction and determination of tricyclic antidepressants in real samples using air-dispersed liquid-liquid microextraction prior to gas chromatography and flame ionization detection.

In the present research, a novel microextraction method was used based on dispersive liquid-liquid microextraction using low-density solvent for the determination of trace amounts of amitriptyline and doxepin as model compounds in human plasma and spring water samples before gas chromatography and flame ionization detection. The parameters influencing the extraction efficiencies including type of the extracting solvent, volume of the aqueous sample solution (donor phase), volume of the extraction solvent (acceptor phase), the number of air-injection, and the effects of pH and ionic strength were optimized. Under the optimized conditions, the obtained enrichment factors were >80. By plotting peak areas of the sample solutions versus various concentrations of the analytes, calibration curves were obtained which show the linear ranges of 10-3000 ng/mL with correlation coefficients of >0.996. The precision of the method was calculated <4.2 and the limit of detection was 1 ng/mL for two analytes. The proposed microextraction method was used for the extraction of the analytes in environmental water and plasma samples and the calculated relative recoveries were all >91%.

A new carbon paste electrode modified with MWCNTs and nano-structured molecularly imprinted polymer for ultratrace determination of trimipramine: The crucial effect of electrode components mixing on its performance.

A novel carbon nanocomposite paste electrode was prepared and used as a voltammetric sensor for ultratrace determination of trimipramine (TRI) which currently used for the treatment of psychiatric disorders. For this aim, nanoparticles of molecularly imprinted polymer (MIP), synthesized by precipitation polymerization method, and multi-walled carbon nanotubes (MWCNTs) were embedded in a nanocomposite paste electrode. The nanocomposite mixing style demonstrated a significant influence on the final electrode performance. The sensor exhibited linear response range of 1.0 × 10-10-2.5 × 10-8 mol L-1 and very high sensitivity of 2131 µA µâ€¯mol L-1. The lower detection limit of the sensor was calculated to be 4.5 × 10-11 mol L-1 (S/N = 3). This sensor was applied successfully for highly selective determination of TRI in pharmaceutical formulations, urine and serum samples without applying any sample pretreatment.

Estimating environmental fate of tricyclic antidepressants in wastewater treatment plant.

TCAs are known to be toxicants and endocrine disrupting agents. Generally, after being used, TCAs are passed through wastewater treatment plants (WWTPs) to be treated. However, still trace amounts (ng/L to µg/L) of TCAs have been founded even in the treated water. Therefore, the aim of this study is to elucidate the environmental behaviors of TCAs in the sewage water from WWTPs (Jeonju, Korea). For the experiments, seven TCAs (amitriptyline, imipramine, clomipramine, desipramine, protriptyline, nortriptyline, and doxepin) were selected. Hydrolysibility, biodegradability, and adsorbability of the selected seven TCAs were evaluated. Based on the results, it was concluded that TCAs are not readily hydrolyzed in water and also not biodegraded by aerobic sludge. The 60% to 85% of TCAs were adsorbed immediately onto the activated sludge within 1 s via electrostatic and hydrophobic interactions. It was clearly observed that adsorption affinities were dependent on the types of activated sludge (i.e. anaerobic and aerobic sludge). The affinities of aerobic and anaerobic sludge towards the TCAs at trace concentrations e.g., 1 to 10 µg/L, were estimated to be in the range from 0.021 ±â€¯0.000 to 0.087 ±â€¯0.000 L/µg and from 0.001 ±â€¯0.000 to 0.108 ±â€¯0.001 L/µg, respectively.

Suitability of 1-hexyl-3-methylimidazolium ionic liquids for the analysis of pharmaceutical formulations containing tricyclic antidepressants.

The reversed-phase chromatographic behaviour of six tricyclic antidepressants (amitryptiline, clomipramine, doxepin, imipramine, nortryptiline and maprotiline) was examined in this work with acetonitrile-water mobile phases, in the absence and presence of the ionic liquids 1-hexyl-3-methylimidazolium chloride and 1-hexyl-3-methylimidazolium tetrafluoroborate, which have interesting features for the separation of basic compounds, in terms of peak shape combined with reduced retention. Tricyclic antidepressants are low polarity drugs that strongly associate to the alkyl chains of conventional stationary phases. They are also positively charged in the usual working pH range (2-8) in reversed-phase liquid chromatography, due to their strong basic character. In consequence, they may interact with the residual ionised silanols present in conventional silica-based stationary phases, which is translated in stronger retention, and tailed and broad peaks. A simple chromatographic procedure for the control of tricyclic antidepressants in pharmaceutical formulations was developed using a C8 column and a mobile phase containing 30% acetonitrile/10 mM 1-hexyl-3-methylimidazolium chloride at pH 3, with UV detection. Intra- and inter-day precisions were usually below +1.0%, and intra- and inter-day bias (trueness) ranged between ‒2.1% and +2.4%, and between ‒3.0% and +2.3%, respectively. Sample preparation was simple and only required solubilisation and filtration previous to injection.

Pharmacokinetic study of tianeptine and its active metabolite MC5 in rats following different routes of administration using a novel liquid chromatography tandem mass spectrometry analytical method.

Tianeptine is an atypical antidepressant with a unique mechanism of action and recently it has been also reported that its major metabolite, compound MC5, possesses pharmacological activity similar to that of the parent drug. The current study aims to investigate the pharmacokinetics (PK) of both tianeptine and MC5 after intravenous or intraperitoneal administration of the parent drug as well as the metabolic ratio of MC5 in rats. To achieve these goals an LC-MS/MS method using the small sample volume for the quantitation of tianeptine and its active metabolite MC5 in rat plasma and liver perfusate has been developed and validated. Following an intravenous administration of tianeptine pharmacokinetic parameters were calculated by non-compartmental analysis. The average tianeptine volume of distribution at steady state was 2.03 L/kg and the systemic clearance equaled 1.84 L/h/kg. The mean elimination half-lives of tianeptine and MC5 metabolite were 1.16 and 7.53 h, respectively. The hepatic clearance of tianeptine determined in the isolated rat liver perfusion studies was similar to the perfusate flow rate despite the low metabolic ratio of MC5. Mass spectrometric analysis of rat bile indicated that tianeptine and MC5 metabolite are eliminated with bile as glucuronide and glutamine conjugates. Bioavailability of tianeptine after its intraperitoneal administration was 69%. The PK model with a metabolite compartment developed in this study for both tianeptine and MC5 metabolite after two routes of administration may facilitate tianeptine dosage selection for the prospective pharmacological experiments.

Metabolism and bioactivation of the tricyclic antidepressant amitriptyline in human liver microsomes and human urine.

AIM: Amitriptyline is a widely used tricyclic antidepressant, but the metabolic studies were conducted almost 20 years ago using high-performance liquid chromatography coupled with ultraviolet detector or radiolabeled methods. RESULTS: First, multiple ion monitoring (MIM)- enhanced product ion (EPI) scan was used to obtain the diagnostic ions or neutral losses in human liver microsome incubations with amitriptyline. Subsequently, predicted multiple reaction monitoring (MRM)-EPI scan was used to identify the metabolites in human urine with the diagnostic ions or neutral losses. Finally, product ion filtering and neutral loss filtering were used as the data mining tools to screen metabolites. Consequently, a total of 28 metabolites were identified in human urine after an oral administration using LC-MS/MS. CONCLUSION: An integrated workflow using LC-MS/MS was developed to comprehensively profile the metabolites of amitriptyline in human urine, in which five N-acetyl-l-cysteine conjugates were characterized as tentative biomarkers for idiosyncratic toxicity.

Dispersion of hydrophobic magnetic nanoparticles using ultarsonic-assisted in combination with coacervative microextraction for the simultaneous preconcentration and determination of tricyclic antidepressant drugs in biological fluids.

A two-step sample preparation technique based on dispersive micro solid-phase extraction combined with coacervative microextraction is presented for preconcentration and determination of tricyclic antidepressant drugs in biological samples. An important feature of the method is the application of hydrophobic magnetic nanoparticles, which in combination with coacervative microextraction method enables development of rapid and efficient extraction procedure in order to achievement of a high extraction efficiency. Simultaneous optimization by experimental design lead to improvement of method with low cost which supply useful information about interaction among variables. Under the optimized conditions, a linear range of 5-1000ngmL(-1) with detection limits from 0.51 to 1.4ngmL(-1) were obtained for target analytes. The method was successfully used for the determination of analytes in biological fluids (plasma and urine) with relative recoveries in the range of 89-105% (RSDs<3.5%).

Determination of tricyclic antidepressants in biota tissue and environmental waters by liquid chromatography-tandem mass spectrometry.

This work describes the optimization, validation, and application in real samples of accurate and precise analytical methods to determine tricyclic antidepressants (TCAs), including amitriptyline, nortriptyline, imipramine, and clomipramine in different environmental matrices, such as water (estuary, seawater, and wastewater treatment plant effluent) and biota (fish muscle, fish liver, and mussels), which would lead to supplement the scarce information on the presence of TCAs in aquatic organisms. The analysis step performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was fully optimized to improve the sensitivity of the separation and detection steps. The extraction of solid samples was accomplished using focused ultrasonic solid-liquid extraction (FUSLE), which required a low amount of sample (0.5 g), solvent (7 mL acetonitrile/H2O, 95:5 v/v) and short extraction time (30 s). In the optimisation of the clean-up step, mixed mode solid-phase extraction (SPE) using a strong cation exchanger rendered clean extracts and the best results in terms of extraction efficiency and matrix effect. The same SPE mode was also used for the extraction and pre-concentration of TCAs from environmental water matrices. The methods afforded satisfactory apparent recovery values (86-122%) and repeatability (RSD < 5%), regardless of the matrix. Finally, the developed methods were applied to the analysis of real samples from the Biscay Coast, where TCAs were detected in both water and biota samples up to 25.9 ng/L and 1.8 ng/g, respectively. Up to our knowledge, this is the first work using FUSLE for the determination of TCAs and one of the few analyzing TCAs in biota samples.

[The determination of amitriptyline and its metabolite, nortriptyline, in the biological objects of the corpse by the high-performance liquid chromatography technique].

Tricyclic antidepressants are among the preparations that most frequently cause intoxication in adults and children; moreover, poisoning with these substances not infrequently has a fatal outcome. Medications belonging to this group, such as amitriptyline, are extensively used to manage manifestations of depression, anxiety, migraine, neuropathic pain, and hyperactivity syndrome. Amitriptyline overdosage causes non-specific symptoms of intoxication, and its clinical picture does not allow to identify the nature of a psychotropic xenobiotic. Of primary importance in connection with this is to establish the cause of intoxication or death by the clinical toxicological and forensic medical methods based on the results of the fast identification and quantitation of amitriptyline in biological materials including blood, urine, hepatic tissues, etc. The authors describe the method for the determination of amitriptyline and its principal physiological metabolite nortriptyline in biological objects with the help of high performance liquid chromatography (HPLC).

[The identification and quantitative measurement of mirtazapine isolated from the biological material by high performance liquid chromatography].

The present study was designed to estimate the effectiveness of isolation of mirtazapine from the liver, blood, and urine. The conditions were developed for the identification and quantitative measurement of the isolated mirtazapine with the use of high performance liquid chromatography and detection from the UV-spectrum and mass-spectrometry. The retention time of mirtazapine isolated from the liver was 2.88 +/- 0.08 min. The straight-line equation within the range of mirtazapine concentrations from 1 to 20 mc/ml was characterized by the dependence: Y = 3.25 x 10(4)X - 6.27 x 10(3) (r = 0.9997). The study showed that it is possible to isolate 46.44 +/- 1.89% of mirtazapine present in the liver and 50.4 +/- 1.05% from blood using extraction by acetonitrile acidified with an 1 M hydrochloric acid solution. Chloroform extraction from urine at pH 7.0-8.0 releases 90.22 +/- 1.88% of mirtazapine.

Application of electro-enhanced solid phase microextraction combined with gas chromatography-mass spectrometry for the determination of tricyclic antidepressants in environmental water samples.

A fast and efficient method for the determination of tricyclic antidepressants using electro-enhanced solid phase microextraction (SPME) coupled to gas chromatography-mass spectrometry (GC-MS) has been developed. One advantage of this approach is that the mass transfer of target analytes from the sample solution to an SPME fiber can be accelerated by the electrical field, improving extraction selectivity and efficiency. In the present work, the target analytes extracted to the SPME fiber were thermally desorbed in the GC injection port after extraction. Under the optimized extraction conditions, the developed method exhibited low limits of detection (between 0.079 and 0.296µg/L) and good linearity over the concentration range of between 1 and 500µg/L with coefficients of determination (r(2)) of between 0.993 and 0.999. The relative standard deviations were lower than 9.2% for all analytes. The proposed method was applied to extract tricyclic antidepressants in environmental water samples.

Applying quantitative structure-activity relationship (QSAR) methodology for modeling postmortem redistribution of benzodiazepines and tricyclic antidepressants.

Postmortem redistribution (PMR) constitutes a multifaceted process, which complicates the interpretation of drug concentrations by forensic toxicologists. The present study aimed to apply quantitative structure-activity relationship (QSAR) analysis for modeling PMR data of structurally related drugs, 10 benzodiazepines and 10 tricyclic antidepressants. For benzodiazepines, an adequate QSAR model was obtained (R(2) = 0.98, Q(2) = 0.88, RMSEE = 0.12), in which energy, ionization and molecular size exerted significant impact. For tricyclic antidepressants, an adequate QSAR model with slightly inferior statistics (R(2) = 0.95, Q(2) = 0.87, RMSEE = 0.29) was established after exclusion of maprotiline, in which energy parameters, basicity character and lipophilicity exerted significant contribution. Thus, QSAR analysis could be used as a complementary tool to provide an informative illustration of the contributing molecular, physicochemical and structural properties in PMR process. However, the complexity, non-static and time-dependent nature of PMR endpoints raises serious concerns whether QSAR methodology could predict the degree of redistribution, highlighting the need for animal-derived PMR data.

Application of a new fiber coating based on electrochemically reduced graphene oxide for the cold-fiber headspace solid-phase microextraction of tricyclic antidepressants.

A new fiber based on the electrochemical reduction of graphene oxide was prepared on a copper wire for solid-phase microextraction (SPME) applications. The prepared fiber was used for the SPME and gas chromatographic analysis of tricyclic antidepressants (TCADs), including amitriptyline, trimipramine, and clomipramine. The feasibility of direct-immersion and headspace modes of SPME for the determination of TCADs was studied. The effects of four parameters including pH, salt content, extraction temperature with and without cooling the fiber, and extraction time were investigated. The comparison showed that headspace cold fiber SPME results in the best outcome for the extraction of TCADs. Under the optimized conditions of this mode, the calibration curves were linear between 2.0 and 500 ng/mL and the detection limits were between 0.30 and 0.53 ng/mL. The intraday and interday RSDs obtained at 20 ng/mL (n = 5), using a single fiber, were 5.5-9.0 and 7.5-9.8, respectively. The fiber to fiber repeatability (n = 4), expressed as the RSD, was between 12.8 and 13.2% at a 20 ng/mL concentration level. The method was successfully applied to the analysis of TCADs in plasma samples showing recoveries from 73 to 96%.

Electrochemical screening of biomembrane-active compounds in water.

Interactions of biomembrane-active compounds with phospholipid monolayers on microfabricated Pt/Hg electrodes in an on-line high throughput flow system are demonstrated by recording capacitance current peak changes as rapid cyclic voltammograms (RCV). Detection limits of the compounds' effects on the layer have been estimated from the data. Compounds studied include steroids, polycyclic aromatic hydrocarbons, tricyclic antidepressants and tricyclic phenothiazines. The results show that the extent and type of interaction depends on the-(a) presence and number of aromatic rings and substituents, (b) presence and composition of side chains and, (c) molecular shape. Interaction is only indirectly related to compound hydrophobicity. For a selection of tricyclic antidepressants and tricyclic phenothiazines the detection limit in water is related to their therapeutic normal threshold. The sensing assay has been tested in the presence of humic acid as a potential interferent and in a tap water matrix. The system can be applied to the screening of putative hazardous substances and pharmaceuticals allowing for early detection thereof in the water supply. The measurements are made in real time which means that potentially toxic compounds are detected rapidly within <10 min per assay. This technology will contribute greatly to environment safety and health.