Selective electrochemical detection of antidepressant drug imipramine in blood serum and urine samples using an antimony telluride-graphite nanofiber electrode.

A high-performance imipramine (IMPR) sensor has been developed  based on metal chalcogenide-carbon composite materials. The antimony telluride-graphite nanofiber (Sb2Te3-GNF, hereafter SBT-GNF) composite was synthesized by the hydrothermal method and confirmed by X-ray powder diffraction (XRD) pattern. The morphology, crystalline lattice, and chemical states were characterized by HRTEM, SAED, and XPS analysis. The characterizations confirmed the formation of an effective composite, SBT-GNF. The SBT-GNF was fabricated as a disposable sensor electrode with a screen-printed carbon electrode (SPCE) and examined for the detection of IMPR by differential pulse voltammetry (DPV). The electroanalytical results of SBT-GNF are compared with the SBT and GNF, and the rational design of effective composite is discussed. SBT-GNF/SPCE showed a good linear range (0.01­51.8 µM), sensitivity (1.35 ± 0.1 µA µM-1 cm-2), and low LOD (4 ± 2 nM). Moreover, the SBT-GNF/SPCE revealed high selectivity and high tolerance limit against potential interfering compounds in blood serum and urine samples. Therefore, this electrochemical sensor can be applicable for the detection of tricyclic antidepressant drug IMPR in clinical and pharmaceutical analysis.

Polyoxomolybdate368 /polyaniline nanocomposite as a novel fiber for solid-phase microextraction of antidepressant drugs in biological samples.

A novel solid-phase microextraction fiber was synthesized by coating a stainless steel wire with polyoxomolybdate368 /polyaniline as a sorbent aimed at extraction of amitriptyline, nortriptyline, and doxepin as antidepressant drugs from urine and blood samples. The polyoxomolybdate368 /polyaniline composite coating was applied using electropolymerization process under constant potential. This composition leads to enhanced extraction efficiency of the fiber. Scanning electron microscopy images show that huge three-dimensional structures of polyoxomolybdate368 in composite induced more non-smooth and porous fiber. In order to optimize of the extraction process, a series of variables including concentration of the composite materials, coating thickness, pH, extraction time, salt addition, and stirring rate was investigated and optimum conditions were determined. Analysis of surface morphology and chemical composition was performed. High-performance liquid chromatography was used for separation and evaluation of mentioned antidepressant drugs from the matrixes. The experiments indicated a detection limits of <0.2 ng/L and a linear dynamic range of 0.3-100 ng/L (R2  > 0.994). The relative recovery values were found to be in the range of 92-98%. It was concluded that the purposed fiber is highly efficient in analyzing traces of antidepressant drugs in urine and blood.

Enhanced pseudotargeted analysis using a segment data dependent acquisition strategy by liquid chromatography-tandem mass spectrometry for a metabolomics study of liquiritin in the treatment of depression.

An enhanced pseudotargeted method using a segment data-dependent acquisition mode based on ultra-high performance liquid chromatography-tandem mass spectrometry was developed. This segment data dependent acquisition-based pseudotargeted method could improve the detection of co-eluted ions and extend the coverage of analytes. A set of 502 multiple reaction monitoring channels were obtained by this segment strategy, which was twice the number created by the traditional data-dependent acquisition mode. Compared with the untargeted method, the pseudotargeted profiling demonstrated higher sensitivity and higher precision. More than 90% of the metabolites detected by the enhanced pseudotargeted method had relative standard deviations less than 15%. The segment data dependent acquisition-based pseudotargeted method was successfully applied to the metabolomics study of the depressed rats with the treatment of liquiritin. Forty-seven differential metabolites were screened and five metabolic pathways were found to be related to depression including retinol metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, terpenoid backbone biosynthesis, and lysine degradation. The segment data dependent acquisition-based pseudotargeted method widened the coverage of metabolites with good sensitivity and precision, which exhibited great potential in the discovery of differential metabolites in metabolomics studies.

Multidimensional Liquid Chromatography Employing a Graphene Oxide Capillary Column as the First Dimension: Determination of Antidepressant and Antiepileptic Drugs in Urine.

Human mental disorders can be currently classified as one of the most relevant health topics. Including in this are depression and anxiety, which can affect us at any stage of life, causing economic and social problems. The treatments involve cognitive psychotherapy, and mainly the oral intake of pharmaceutical antidepressants. Therefore, the development of analytical methods for monitoring the levels of these drugs in biological fluids is critical. Considering the current demand for sensitive and automated analytical methods, the coupling between liquid chromatography and mass spectrometry, combined with suitable sample preparation, becomes a useful way to improve the analytical results even more. Herein we present an automated multidimensional method based on high-performance liquid chromatography-tandem mass spectrometry using a lab-made, graphene-based capillary extraction column connected to a C8 analytical column to determined five pharmaceutical drugs in urine. A method enhancement was performed by considering the chromatographic separation and the variables of the loading phase, loading time, loading flow, and injection volume. Under optimized conditions, the study reports good linearity with R2 > 0.98, and limits of detection in the range of 0.5-20 µg L-1. Afterward, the method was applied to the direct analysis of ten untreated urine samples, reporting traces of citalopram in one of them. The results suggest that the proposed approach could be a promising alternative that provides direct and fully automated analysis of pharmaceutical drugs in complex biological matrices.

Microextraction by packed sorbent followed by ultra high performance liquid chromatography for the fast extraction and determination of six antidepressants in urine.

The growing use of antidepressants in recent years has led to their increasing presence in forensic analyses. In this work, microextraction by packed sorbent followed by ultra-performance liquid chromatography with photodiode array detection provided a fast method for determining the antidepressants mirtazapine, venlafaxine, escitalopram, fluoxetine, fluvoxamine, and sertraline in human urine. The microextraction conditions (viz., type of sorbent, number of draw-eject extraction cycles or strokes, sample volume and pH, and type and volume of washing solution and eluent) were optimized by using an experimental design. The ensuing analytical method was validated in terms of linearity (25-1000 ng/mL urine), limit of detection (lower than 7.1 ng/mL), limit of quantification (25 ng/mL), precision (4.7-15.1% as relative standard deviation), and accuracy (80.4-126.1% as mean recovery for four replicate determinations). The proposed method allowed the six target antidepressants to be determined at concentrations from therapeutic to toxic levels. The application to small volumes (300 µL) of urine afforded fast extraction of the analytes and provided results on a par with those of existing clinical and forensic alternatives.

Extraction of antidepressant drugs in biological samples using alkanol-based nano structured supramolecular solvent microextraction followed by gas chromatography with mass spectrometric analysis.

In the present study, a supramolecular solvent was formed from reverse micelle aggregates of octanol. The proposed supramolecular solvent was used for rapid extraction of some antidepressants drugs including amitriptyline, imipramine, desipramine, maprotiline, sertraline, and doxepin from biological samples. Alkanol-based supramolecular solvents have a unique array of physicochemical properties, making them a very attractive alternative to replace organic solvents in analytical extractions. The parameters affecting the extraction of target analytes (i.e., the volume of tetrahydrofuran and octanol as the major components comprising the supramolecular solvent, chain length of alkanols, sample solution pH, salt addition, and ultrasonic time) were investigated and optimized by factor by factor optimization method. Under the optimum conditions, preconcentration factors of 470, 490, 460, 385, 370, and 430 were obtained for amitriptyline, doxepin, imipramine, desipramine, maprotiline, and sertraline, respectively. The linear ranges and coefficients of determination (R2 ) were obtained in the range of 0.01-100 µg/L and 0.9974-0.9991, respectively. Also the limits of detection (S/N = 3) of 0.003-0.03 µg/L, and precisions (n = 5) of 4.9-8.9% were calculated. Finally, the method was successfully applied for the extraction of antidepressant drugs in biological samples, and relative recoveries in the range of 91-102% were obtained.

Carbon nanotube-modified monolithic polymethacrylate pipette tips for (micro)solid-phase extraction of antidepressants from urine samples.

This work evaluates the potential of methacrylate monoliths with multi-walled carbon nanotubes incorporated into the polymeric network for the extraction of antidepressants from human urine. The method is based on a micropipette solid-phase extraction tip containing a hybrid monolithic material covalently attached to the polypropylene housing. A polymer layer made from poly(ethylene dimethacrylate) was bound to the inner surface of a polypropylene tip via UV grafting. The preparation of the monolith and the microextraction steps were optimized in terms of adsorption capacity. Limits of detection ranged from 9 to 15 µg·L-1. The average precision of the method varied between 3 and 5% (intra-tips), and from 4 to 14% (inter-tips). The accuracy of the method was evaluated through a recovery study by using spiked samples. Graphical abstract Hybrid polymer monoliths containing multi-walled carbon nanotubes (MWCNTs) were prepared in pipette tips by photo-polymerization approach. The extraction devices were used for the extraction of antidepressants in urine samples.

Carbon Nanohorn Suprastructures on a Paper Support as a Sorptive Phase.

This article describes a method for the modification of paper with single-wall carbon nanohorns (SWCNHs) to form stable suprastructures. The SWCNHs form stable dahlia-like aggregates in solution that are then self-assembled into superior structures if the solvent is evaporated. Dipping paper sections into a dispersion of SWCNHs leads to the formation of a thin film that can be used for microextraction purposes. The coated paper can be easily handled with a simple pipette tip, paving the way for disposable extraction units. As a proof of concept, the extraction of antidepressants from urine and their determination by direct infusion mass spectrometry is studied. Limits of detection (LODs) were 10 ng/L for desipramine, amitriptyline, and mianserin, while the precision, expressed as a relative standard deviation, was 7.2%, 7.3%, and 9.8%, respectively.

Magnetic micro-solid-phase extraction based on magnetite-MCM-41 with gas chromatography-mass spectrometry for the determination of antidepressant drugs in biological fluids.

A new facile magnetic micro-solid-phase extraction coupled to gas chromatography and mass spectrometry detection was developed for the extraction and determination of selected antidepressant drugs in biological fluids using magnetite-MCM-41 as adsorbent. The synthesized sorbent was characterized by several spectroscopic techniques. The maximum extraction efficiency for extraction of 500 µg/L antidepressant drugs from aqueous solution was obtained with 15 mg of magnetite-MCM-41 at pH 12. The analyte was desorbed using 100 µL of acetonitrile prior to gas chromatography determination. This method was rapid in which the adsorption procedure was completed in 60 s. Under the optimized conditions using 15 mL of antidepressant drugs sample, the calibration curve showed good linearity in the range of 0.05-500 µg/L (r2  = 0.996-0.999). Good limits of detection (0.008-0.010 µg/L) were obtained for the analytes with good relative standard deviations of <8.0% (n = 5) for the determination of 0.1, 5.0, and 500.0 µg/L of antidepressant drugs. This method was successfully applied to the determination of amitriptyline and chlorpromazine in plasma and urine samples. The recoveries of spiked plasma and urine samples were in the range of 86.1-115.4%. Results indicate that magnetite micro-solid-phase extraction with gas chromatography and mass spectrometry is a convenient, fast, and economical method for the extraction and determination of amitriptyline and chlorpromazine in biological samples.

Separation and identification of antidepressants by acrylate-based monolithic column capillary electrochromatography with UV detection.

This paper details a method for separation and identification of six antidepressant compounds using an acrylate-based porous monolithic capillary. Detection takes place using CEC coupled with UV or mass spectrometric detection. The CEC-UV method provides an effective and efficient method for the separation and identification of the analytes. Spiked urine samples were utilized to check method capability, and a liquid-liquid extraction procedure was developed to perform sample extraction. Detection limits ranged from 10 to 30 ng/mL.

Glycine functionalized multiwall carbon nanotubes as a novel hollow fiber solid-phase microextraction sorbent for pre-concentration of venlafaxine and o-desmethylvenlafaxine in biological and water samples prior to determination by high-performance liquid chromatography.

A hollow fiber solid-phase microextraction method for pre-concentration of venlafaxine and o-desmethylvenlafaxine in biological matrices is described for the first time. The functionalized MWCNTs with an amino acid, glycine, were synthesized and held in the pore of a hollow fiber by sol-gel technique. In order to extract venlafaxine and o-desmethylvenlafaxine from real samples, the hollow fiber was immersed into the sample solution under a magnetic stirring for 20 min. The extracted venlafaxine and o-desmethylvenlafaxine from the fibers were then desorbed with methanol by sonication and analyzed using high-performance liquid chromatography. Important microextraction parameters including pH of donor phase, donor phase volume, stirring rate, extraction time, and desorption conditions such as the type and volume of solvents and desorption time were thoroughly investigated and optimized. The optimized technique provides good repeatability (RSD of the intraday precision 3.7 and 3.4, interday precision of 5.8 and 5.4 %), linearity of (0.1-300 and 0.2-360 ng mL(-1)), low LODs of (0.03 and 0.07 ng mL(-1)), and high enrichment factor of (164 and 176) for venlafaxine and o-desmethylvenlafaxine, respectively. The analytical performance of Gly-MWCNTs as a new SPME sorbent was compared with MWCNTs and carboxylic MWCNTs. The results indicate that Gly-MWCNTs are quite effective for extraction of venlafaxine and o-desmethylvenlafaxine. Feasibility of the method was evaluated by analyzing human urine and real water samples. The results obtained in this work show a promising, simple, selective, and sensitive sample preparation and determination method for biological and water samples.

Magnetic solid phase extraction coupled with desorption corona beam ionization-mass spectrometry for rapid analysis of antidepressants in human body fluids.

Ambient ionization techniques show good potential in rapid analysis of target compounds. However, a direct application of these ambient ionization techniques for the determination of analytes in a complex matrix is difficult due to the matrix interference and ion suppression. To resolve this problem, here we developed a strategy by coupling magnetic solid phase extraction (MSPE) with desorption corona beam ionization (DCBI)-mass spectrometry (MS). As a proof of concept, the pyrrole-coated Fe3O4 magnetic nanoparticles (Fe3O4@Ppy) were prepared and used for the extraction of antidepressants. After extraction, the Fe3O4@Ppy with trapped antidepressants was then directly subjected to DCBI-MS analysis with the aid of a homemade magnetic glass capillary. As the MSPE process is rapid and the direct DCBI-MS analysis does not need solvent desorption or chromatographic separation processes, the overall analysis can be completed within 3 min. The proposed MSPE-DCBI-MS method was then successfully used to determine antidepressants in human urine and plasma. The calibration curves were obtained in the range of 0.005-0.5 µg mL(-1) for urine and 0.02-1 µg mL(-1) for plasma with reasonable linearity (R(2) > 0.951). The limits of detection of three antidepressants were in the range of 0.2-1 ng mL(-1) for urine and 2-5 ng mL(-1) for plasma. Acceptable reproducibility for rapid analysis was achieved with relative standard deviations less than 19.1% and the relative recoveries were 85.2-118.7%. Taken together, the developed MSPE-DCBI-MS strategy offers a powerful capacity for rapid analysis of target compounds in a complex matrix, which would greatly expand the applications of ambient ionization techniques with plentiful magnetic sorbents.

Determination of three antidepressants in urine using simultaneous derivatization and temperature-assisted dispersive liquid-liquid microextraction followed by gas chromatography-flame ionization detection.

This paper presents a fast and simple method for the extraction, preconcentration and determination of fluvoxamine, nortriptyline and maprotiline in urine using simultaneous derivatization and temperature-assisted dispersive liquid-liquid microextraction (TA-DLLME) followed by gas chromatography-flame ionization detection (GC-FID). An appropriate mixture of dimethylformamide (disperser solvent), 1,1,2,2-tetrachloroethane (extraction solvent) and acetic anhydride (derivatization agent) was rapidly injected into the heated sample. Then the solution was cooled to room temperature and cloudy solution formed was centrifuged. Finally a portion of the sedimented phase was injected into the GC-FID. The effect of several factors affecting the performance of the method, including the selection of suitable extraction and disperser solvents and their volumes, volume of derivatization agent, temperature, salt addition, pH and centrifugation time and speed were investigated and optimized. Figures of merit of the proposed method, such as linearity (r(2) > 0.993), enrichment factors (820-1070), limits of detection (2-4 ng mL(-1)) and quantification (8-12 ng mL(-1)), and relative standard deviations (3-6%) for both intraday and interday precisions (concentration = 50 ng mL(-1)) were satisfactory for determination of the selected antidepressants. Finally the method was successfully applied to determine the target pharmaceuticals in urine.

Development and validation of a sensitive spectrofluorimetric method for the determination of amoxapine in human plasma and urine.

A selective and sensitive spectrofluorimetric method was developed and validated for the determination of amoxapine in human plasma and urine. The developed method is based on labeling with 5-dimethylaminonaphthalene-1-sulfonyl chloride (dansyl chloride) and monitoring at 397 nm (excitation)/514 nm (emission). The method was validated for linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, recovery and robustness. The calibration curves were linear over a concentration range of 250-2500 and 50-1250 ng/mL for plasma and urine, respectively. The LOD values were calculated to be 13.31 and 13.17 ng/mL for plasma and urine, respectively. The proposed method was applied to study of amoxapine in human plasma and urine.

An investigation of the antidepressant action of xiaoyaosan in rats using ultra performance liquid chromatography-mass spectrometry combined with metabonomics.

A rapid, highly sensitive, and selective method was applied in a non-invasive way to investigate the antidepressant action of Xiaoyaosan (XYS) using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) and chemometrics. Many significantly altered metabolites were used to explain the mechanism. Venlafaxine HCl and fluoxetine HCl were used as chemical positive control drugs with a relatively clear mechanism of action to evaluate the efficiency and to predict the mechanism of action of XYS. Urine obtained from rats subjected to chronic unpredictable mild stress (CUMS) was analyzed by UPLC-MS. Distinct changes in the pattern of metabolites in the rat urine after CUMS production and drug intervention were observed using partial least squares-discriminant analysis. The results of behavioral tests and multivariate analysis showed that CUMS was successfully reproduced, and a moderate-dose XYS produced significant therapeutic effects in the rodent model, equivalent to those of the positive control drugs, venlafaxine HCl and fluoxetine HCl. Metabolites with significant changes induced by CUMS were identified, and 17 biomarker candidates for stress and drug intervention were identified. The therapeutic effect of XYS on depression may involve regulation of the dysfunctions of energy metabolism, amino acid metabolism, and gut microflora changes. Metabonomic methods are valuable tools for measuring efficacy and mechanisms of action in the study of traditional Chinese medicines.

Development of the first metabolite-based LC-MS(n) urine drug screening procedure-exemplified for antidepressants.

In contrast to GC-MS libraries, currently available LC-MS libraries for toxicological detection contain besides parent drugs only some main metabolites limiting their applicability for urine screening. Therefore, a metabolite-based LC-MS(n) screening procedure was developed and exemplified for antidepressants. The library was built up with MS(2) and MS(3) wideband spectra using an LXQ linear ion trap with electrospray ionization in the positive mode and full-scan information-dependent acquisition. Pure substance spectra were recorded in methanolic solution and metabolite spectra in urine from rats after administration of the corresponding drugs. After identification, the metabolite spectra were added to the library. Various drugs and metabolites could be sufficiently separated. Recovery, process efficiency, matrix effects, and limits of detection for selected drugs were determined using protein precipitation. Automatic data evaluation was performed using ToxID and SmileMS software. The library consists of over 700 parent compounds including 45 antidepressants, over 1,600 metabolites, and artifacts. Protein precipitation led to sufficient results for sample preparation. ToxID and SmileMS were both suitable for target screening with some pros and cons. In our study, only SmileMS was suitable for untargeted screening being not limited to precursor selection. The LC-MS(n) method was suitable for urine screening as exemplified for antidepressants. It also allowed detecting unknown compounds based on known fragment structures. As ion suppression can never be excluded, it is advantageous to have several targets per drug. Furthermore, the detection of metabolites confirms the body passage. The presented LC-MS(n) method complements established GC-MS or LC-MS procedures in the authors' lab.

Electrospray ionization-ion mobility spectrometry as a detection system for three-phase hollow fiber microextraction technique and simultaneous determination of trimipramine and desipramine in urine and plasma samples.

A novel method based on three-phase hollow fiber microextraction technique (HF-LPME) coupled with electrospray ionization-ion mobility spectrometry (ESI-IMS) was developed for the simultaneous determination of two antidepressant drugs (trimipramine and desipramine) in urine and plasma samples. The effects of various parameters such as type of organic solvent, composition of donor and acceptor phase, stirring rate, salt addition, extraction time, and temperature were investigated. Under the optimized conditions, the relative standard deviation was in the range of 5-6%, and the method quantitation limit (MQL) of utilizing HF-LPME/ESI-IMS was 5 µg/L for both drugs. The relative recoveries obtained by the proposed method from urine and plasma samples were in the range 94% to 97% for trimipramine and 92% to 96% for desipramine. Finally, the feasibility of the proposed method was successfully confirmed by extraction and determination of trace amounts of trimipramine and desipramine in biological samples without any significant matrix effect.

Ultrasound-assisted emulsification microextraction based on solidification of floating organic droplet combined with HPLC-UV for the analysis of antidepressant drugs in biological samples.

Ultrasound-assisted emulsification microextraction based on the solidification of floating organic droplet combined with high-performance liquid chromatography-ultra violet (HPLC-UV) detection was applied for the extraction and determination of fluoxetine, citalopram, and venlafaxine as antidepressants drugs in biological samples. In total, 30 µL of undecanol was injected slowly into a glass-centrifuge tube containing 5 mL alkaline sample solution that was located inside the ultrasonic water bath. The formed emulsion was centrifuged and the fine droplets of solvent were floated at the top of the test tube. The test tube was then cooled in an ice bath and the solidified solvent transferred into a conical vial; it melted quickly at room temperature. Then the analysis of the extracts was carried out by high-performance liquid chromatography. Under optimal conditions, the preconcentration factors were between 174 and 316. Detection limits (LODs) of 3 µg/L were obtained and the calibration graphs were linear within the range of 10-1000 µg/L. Finally, the feasibility of the proposed method was successfully confirmed by extraction and determination of the antidepressant drugs in human urine and plasma samples in the range of microgram per liter and suitable results were obtained.

Sensitive determination of Fluoxetine and Citalopram antidepressants in urine and wastewater samples by liquid chromatography coupled with photodiode array detector.

A new analyte separation and preconcentration method for the trace determination of antidepressant drugs, Fluoxetine (FLU) and Citalopram (CIT) in urine and wastewaters, was developed based on HPLC-DAD analysis after magnetic solid phase extraction (MSPE). In the proposed method, FLU and CIT were retained on the newly synthetized magnetic sorbent (Fe3O4@PPy-GO) in the presence of buffer (pH 10.0) and then were desorbed into a lower volume of acetonitrile prior to the chromatographic determinations. Before HPLC analysis, all samples were filtered through a 0.45 µm PTFE filter. Experimental parameters such as interaction time, desorption solvent and volume, and pH were studied and optimized in order to establish the detection limit, linearity, enrichment factor and other analytical figures of merit under optimum operation conditions. In the developed method, FLU and CIT were analyzed by diode array detector at the corresponding maximum wavelengths of 227 and 238 nm, respectively, by using an isocratic elution of 60% pH 3.0 buffer, 30% acetonitrile, and 10% methanol. By using the optimum conditions, limit of detections for FLU and CIT were 1.58 and 1.43 ng mL-1, respectively, while the limit of quantifications was 4.82 and 4.71 ng mL-1, respectively. Relative standard deviations (RSD%) for triplicate analyses of model solutions containing 100 ng mL-1 target molecules were found to be less than 5.0 %. Finally, the method was successfully applied to urine (both simulated and real healthy human) and wastewater samples, and quantitative results were obtained in recovery experiments.