Dextrin-assisted gel electromembrane extraction of chiral drugs: Improving the extraction efficiency and investigation of enantioselectivity of extraction.

The present study investigates the use of dextrins (maltodextrin, ß-cyclodextrin, and hydroxypropyl-ß-cyclodextrin) to improve the efficiency of the agarose-based gel electromembrane extraction technique for extracting chiral basic drugs (citalopram, hydroxyzine, and cetirizine). Additionally, it examines the enantioselectivity of the extraction process for these drugs. To achieve these, dextrins were incorporated into either the sample solution, the membrane, or the acceptor solution, and then the extraction procedure was performed. Enantiomers were separated and analyzed using a capillary electrophoresis device equipped with a UV detector. The results obtained under the optimal extraction conditions (sample solution pH: 4.0, acceptor solution pH: 2.0, gel membrane pH: 3.0, agarose concentration: 3 % w/v, stirring rate: 1000 rpm, gel thickness: 4.4 mm, extraction voltage: 62.3 V, and extraction time: 32.1 min) indicated that incorporating dextrins into either the sample solution, membrane or the acceptor solution enhances extraction efficiency by 17.3-23.1 %. The most significant increase was observed when hydroxypropyl-ß-cyclodextrin was added to the acceptor solution. The findings indicated that the inclusion of hydroxypropyl-ß-cyclodextrin in the sample solution resulted in an enantioselective extraction, yielding an enantiomeric excess of 6.42-7.14 %. The proposed method showed a linear range of 5.0-2000 ng/mL for enantiomers of model drugs. The limit of detection and limit of quantification for all enantiomers were found to be < 4.5 ng/mL and <15.0 ng/mL, respectively. Intra- and inter-day RSDs (n = 4) were less than 10.8 %, and the relative errors were less than 3.2 % for all the enantiomers. Finally, the developed method was successfully applied to determine concentrations of enantiomers in a urine sample with relative recoveries of 96.8-99.2 %, indicating good reliability of the developed method.

Facile extraction and determination of organophosphorus pesticides using poly (8-hydroxyquinoline) functionalized magnetic multi-walled carbon nanotubes nanocomposite in water, fruits, and vegetables samples.

This study presents a dispersive micro-solid phase extraction (D-µ-SPE) approach for extracting and determining of two organophosphorus pesticides (OPPs), including diazinon and chlorpyrifos as model analytes in various samples. For this purpose, we synthesized, characterized, and utilized magnetic multi-walled carbon nanotubes coated with poly 8-hydroxyquinoline (MWCNTs/Fe3O4@PHQ) as a novel sorbent. The impact of various parameters, including sorbent type, sample pH, sample volume, sorbent amount, desorption solvent (type and volume), extraction time, and ionic strength on the extraction efficiency was investigated and optimized. Following the extraction, the desorbed pesticides in acetone were analyzed using gas chromatography with an FID detector. Under the optimized experimental conditions, the proposed method showed excellent linearity in the range of 3-1000 µg/L, low detection limit (0.9-1.5 µg/L), good relative recoveries (86-101.5 %), and high precision (RSD < 6.5 %). Finally, the applicability of this method was evaluated by analyzing the target OPPs in a variety of real samples, and obtained satisfactory results.

Dispersive magnetic solid phase extraction of triazole fungicides based on polybenzidine/magnetic nanoparticles in environmental samples.

A polybenzidine-modified Fe3O4@SiO2 nanocomposite was successfully synthesized through a chemical oxidation method and employed as a novel sorbent in dispersive magnetic solid phase extraction (DMSPE) for the preconcentration and determination of three triazole fungicides (TFs), namely diniconazole, tebuconazole, and triticonazole in river water, rice paddy soil, and grape samples. The synthesis method involved a polybenzidine self-assembly coating on Fe3O4@SiO2 magnetic composite. Characterization techniques such as FT-IR, XRD, FESEM, EDX, and VSM were used to confirm the correctness of the synthesized nano-sorbent. The target TFs were determined in actual samples using the synthesized nanocomposite sorbent in combination with gas chromatography-flame ionization detection (FID). Several variables were carefully optimized , including the sample pH, sorbent dosage, extraction time, ionic strength, and desorption condition (solvent type, volume, and time). Under the optimized experimental conditions, the method exhibited linearity in the concentration range 5-1000 ng mL-1 for triticonazole and 2-1000 ng mL-1 for diniconazole and tebuconazole. The limits of detection (LOD) for the three TFs were in the range 0.6-1.5 ng mL-1. The method demonstrated acceptable precision with intra-day and inter-day relative standard deviation (RSD) values of less than 6.5%. The enrichment factors ranged from 248 to 254. Finally, the method applicability was evaluated by determining TFs in river water, rice paddy soil, and grape samples with recoveries in the range 90.5-106, indicating that the matrix effect was negligible in the proposed DMSPE procedure.

Carboxymethylated maltodextrin as a chiral selector for the separation of some basic drug enantiomers using capillary electrophoresis.

In this work, carboxymethylated maltodextrin (Cm-MD) was successfully synthesized as an efficient anionic chiral selector and applied for the enantiomer separation of some basic drugs including tramadol, venlafaxine, verapamil, hydroxyzine, citalopram, fluoxetine, and amlodipine by capillary electrophoresis (CE). The synthesized chiral selector was characterized by the nuclear magnetic resonance and Fourier transform infrared spectrophotometry. Under the optimized Cm-MD modified CE conditions (background electrolyte: phosphate buffer (pH 5.0, 50 mM) containing 5% (w/v) Cm-MD; applied voltage: 20 kV; and capillary column temperature: 25 °C), successful enantiomer separation of all studied chiral drugs were observed. By comparison of Cm-MD and MD for enantiomer separation of the model drugs, it was revealed that Cm-MD exhibits a higher resolution in comparison to the MD modified CE. This enhanced resolution could be attributed to the electrostatic interactions between the cationic drugs and anionic Cm-MD and opposite direction mobility of the host-guest complex relative to the chiral analyte. The optimized Cm-MD modified CE method was successfully used for the assay of the enantiomers of citalopram and venlafaxine in commercial tablets. The proposed method showed the linear range of 5.0-150.0 mg/L and 10.0-150.0 mg/L for both enantiomers of citalopram and venlafaxine, respectively. The limits of quantification were 5.0 and 10.0 mg/L for the enantiomers of citalopram and venlafaxine, respectively. The limit of detection for all enantiomers was found to be < 3.0 mg/L. Intra- and inter-day RSDs (n = 4) were less than 9.7%. The relative errors were less than 9.4% for all enantiomers. The obtained results in this research show that Cm-MD as a new, efficient and inexpensive chiral selector can be used for enantiomer separation of basic drugs using the CE technique.

Miniaturized on-chip electromembrane extraction with QR code-based red-green-blue analysis using a customized Android application for copper determination in environmental and food samples.

A miniaturized on-chip electromembrane extraction device with QR code-based red-green-blue analysis was designed to determine copper in water, food, and soil. The acceptor droplet consisted of ascorbic acid as the reducing agent and bathocuproine as the chromogenic reagent. The formation of a yellowish-orange complex was a sign of copper in the sample. Then, the qualitative and quantitative analysis of the dried acceptor droplet was done by the customized Android app that was developed based on image analysis concepts. In this application, principal component analysis was performed on the data for the first time to reduce the three dimensions, red, green, and blue, to one dimension. The effective extraction parameters were optimized. The limit of detection and limit of quantification were 0.1 µg mL-1. Intra- and inter-assay relative standard deviations ranged between 2.0 and 2.3 % and 3.1-3.7 %, respectively. The calibration range was studied between 0.1 and 25 µg mL-1 (R2 = 0.9814).

Fabrication of Co3O4 quantum dot incorporated polyacrylamide ethylene glycol dimethacrylate as a new fiber for solid phase microextraction and trace determination of organophosphorus pesticides in environmental water samples.

In this paper, a novel solid phase microextraction fiber based on Co3O4 quantum dot incorporated polyacrylamide-co-ethylene glycol dimethacrylate followed by corona discharge ion mobility spectrometry is presented for the trace determination of organophosphorus pesticides in environmental water samples. Ion mobility spectrometry is a comparatively inexpensive, well-known, robust, and easy to operate analytical instrument. This combination would provide a low-cost, fast, selective, and sensitive quantitative system for detection of organophosphorus pesticides. In order to obtain the best extraction efficiency, the optimization of parameters affecting this method was carried out. After optimization, a solution pH of 7.0, extraction temperature of 60 °C, adsorption temperature of 260 °C, extraction time of 30 min, stirring speed of 750 rpm, and ionic strength of 10% w/w were obtained. Consequently, the presented method showed low limits of detection (0.3-0.6 ng mL-1), excellent enrichment factors (PF = 221-263), good linearity (R2 > 0.995), and repeatabilities (intra-day: 3.4 to 4.8%) and (inter-day: 4.7 to 6.1%). The reproducibility (RSD% of fiber to fiber) was also investigated by analyzing three as-prepared fibers under the same conditions and was found to be less than 7.6%. Finally, the developed fiber was used for determination of organophosphorus pesticides in the field samples.

Gelatin microsphere coated Fe3O4@graphene quantum dots nanoparticles as a novel magnetic sorbent for ultrasound-assisted dispersive magnetic solid-phase extraction of tricyclic antidepressants in biological samples.

Gelatin microsphere-coated Fe3O4@graphene quantum dots (Fe3O4@GQD@GM) were designed and synthesized as a novel sorbent via ultrasonic-assisted dispersive magnetic solid-phase extraction (UA-DMSPE) method. The synthesized sorbent was identified and confirmed by FT-IR, XRD, VSM, and SEM techniques. UA-DMSPE was combined with corona discharge ion mobility spectrometry for trace determination of desipramine, sertraline, and citalopram. Effective parameters were considered and optimized. The proposed method, under optimal conditions, showed excellent linearity in different concentration ranges (2-700 ng mL-1, R2 > 0.995), repeatability (RSD < 5.1%), good sensitivity (LODs in the range 0.6-1.5 ng mL-1), high preconcentration factor (PF = 207-218), and acceptable relative recoveries (93.5-101.8%). Eventually, this method was used to determine tricyclic antidepressants in various biological samples. Schematic presentation of the microextraction and monitoring of TCAs by ultrasonic-assisted dispersive magnetic solid phase microextraction-ion mobility spectrometry producer.

A mesoporous nanosorbent composed of silica, graphene, and palladium (II) for ultrasound-assisted dispersive solid-phase extraction of organophosphorus pesticides prior to their quantitation by ion mobility spectrometry.

A new ultrasonic-assisted dispersive solid-phase extraction method using mesoporous nanosorbent composed of silica, graphene, and palladium (II) (M S/G@-SH@Pd (II)), coupled with corona discharge ion mobility spectrometry, was developed for trace determination of organophosphorus pesticides. Initially, the M S/G@-SH@Pd (II) nanosorbent was synthesized and characterized. Then, the nanosorbent was used for the sorption and extraction of organophosphorus pesticides. Under the optimized conditions (pH = 7.0, 15 mg of sorbent, 3 min extraction time, ethanol as desorption agent, 3 min centrifuge time), the proposed technique provided good linearity (R2 > 0.994), repeatability (RSD < 4.6%), low limits of detection (0.15-0.30 ng mL-1), excellent preconcentration factor (PF = 472-478), and high recoveries (93-94%). The method was applied to the determination of organophosphorus pesticides in real water samples. The sorbent was reused in 5 cycles without any considerable loss of activity. Graphical abstract Schematic presentation of design and synthesis of mesoporous nanosorbent composed of silica, graphene, and palladium (II) for ultrasound-assisted dispersive solid-phase extraction of organophosphorus pesticides prior to their quantitation by ion mobility spectrometry.

Simultaneous enantioseparation of nonsteroidal anti-inflammatory drugs by a one-dimensional liquid chromatography technique using a dynamically coated chiral porous silicon pillar array column.

The preparation of a highly efficient chiral liquid chromatography (LC) column is explored by dynamically coating a reversed-phase porous silicon pillar array column with hydroxypropyl-ß-cyclodextrin (Hp-ß-CD) as the chiral selector. Analyte mixtures composed of non-steroidal anti-inflammatory drugs were tested to reveal the enantioseparation potential of the column. The mechanism of chiral discrimination was investigated. The adsorbed Hp-ß-CDs on the column surface experience different interaction with enantiomers. The chiral stationary phase showed satisfying stability and could be easily restored by recovering the selector with sufficient flushing and repeating the loading procedure. The peak capacity of the column was evaluated, and it was found high enough to separate three enantiomer couples using a one-dimensional LC technique.

Electrospun terpolymeric nanofiber membrane for micro solid-phase extraction of diazinon and chlorpyrifos from aqueous samples.

The present study deals with the synthesis and electrospining of a new terpolymer nanofiber in order to determine the amount of diazinon and chlorpyrifos in water and fruit juice samples. The synthesized terpolymer and the prepared nanofiber were characterized using 1 H NMR spectroscopy, FTIR spectroscopy, scanning electron microscopy, and gel permeation chromatography. The performance of terpolymer nanofiber, prepared as a sorbent for micro solid phase extraction was investigated for the extraction of diazinon and chlorpyrifos from aquaeous media. Then, the target analytes were desorbed from the coating with an organic solvent and analyzed by gas chromatography with flame ionization detector. Extraction efficiencies were significant (>90%) under the optimum condition. The proposed method also demonstrated good linear dynamic ranges for diazinon and chlorpyrifos (3-250 and 5-200 µg/L), and low limit of detections (0.5 and 0.7 µg/L) respectively. Moreover, under optimum condition for extraction of diazinon and chlorpyrifos, square of correlation coefficients (R2 ) of 0.9978 and 0.9953 and relative standard deviations of 4.6 and 5.1% were achieved, respectively. The recoveries for diazinon and chlorpyrifos were in the range of 85-97%.

Recent advances in microextraction procedures for determination of amphetamines in biological samples.

Amphetamine and its related derivatives have stimulant and hallucinogenic properties. Illegal use of these drugs is an increasing global problem resulting in significant public health and legal problems. Deaths have been reported after intake of these drugs due to overdose. It is important to determine the type and concentration of illicit drugs in biological samples. These compounds are found in complex matrices at low concentration levels. The microextraction techniques are dominant sample preparation procedure and they are widely accepted as the most labor-intensive part of the bioanalytical process. For this purpose, a survey of recent published advances in microextraction procedures for quantification of amphetamines in biological samples found in the different databases from 2008 to date will be conducted.

Ultrasound assisted dispersive solid phase extraction of triazole fungicides by using an N-heterocyclic carbene copper complex supported on ionic liquid-modified graphene oxide as a sorbent.

An ultrasound-assisted method is described for dispersive solid phase extraction of trace levels of triazole fungicides. A sorbent was prepared from an N-heterocyclic carbene copper complex that was supported on ionic liquid-modified graphene oxide. The sorbent was characterized by scanning electron microscopy, transmission electron microscopy, Raman and FT-IR spectroscopy, energy-dispersive X-ray spectroscopy and elemental mapping. The capability of sorption and extraction is mainly based on complexation with Cu (I) ions. The variables affecting extraction were optimized. Following desorption with ethanol, the fungicides were quantified by corona discharge ion mobility spectrometry. Under optimized conditions (solution pH value: 7.0; amount of sorbent: 10 mg; extraction time: 3 min; desorption agent: ethanol), the technique provides good linearity (>0.994), repeatability (RSD < 4.1%), low limits of detection (0.18 ng.mL-1), excellent preconcentration factors (468-476) and high recoveries from spiked environmental water samples (92-94%). The sorbent can be reused over five cycles without significant loss of its activity. Graphical abstract Schematic presentation of design and synthesis of the N-heterocyclic carbene copper complex supported on ionic liquid-modified graphene oxide as a sorbent for triazole fungicides and its application in ultrasound-assisted dispersive solid phase extraction with ion mobility spectrometric detection.

Development and application of SBA-15 assisted electromembrane extraction followed by corona discharge ion mobility spectrometry for the determination of Thiabendazole in fruit juice samples.

A new sample preparation method based on SBA-15 assisted electromembrane extraction coupled with corona discharge ion mobility spectrometer was developed for the determination of Thiabendazole as a model basic pesticide in fruit juice samples. The addition of SBA-15 in the supported liquid membrane in electromembrane extraction system not only can lead to enhancement of the effective surface area, but also introducing the negatively charged silanol groups into supported liquid membrane might improve migration of positively charged analytes toward the supported liquid membrane and finally into the acceptor solution. To investigate the effect of the presence of SBA-15 in the supported liquid membrane on the extraction efficiency, a comparative study was carried out between the conventional electromembrane extraction and SBA-15/electromembrane extraction methods. Under the optimized conditions, SBA-15/electromembrane extraction method showed higher extraction efficiencies in comparison with conventional electromembrane extraction method. SBA-15/electromembrane extraction method exhibited a low limit of detection (0.9 ng/mL), high preconcentration factor (167) and high recovery (83%). Finally, the applicability of SBA-15/electromembrane extraction method was studied by the extraction and determination of Thiabendazole as a model basic pesticide in fruit juice samples.

Simultaneous chiral separation of tramadol and methadone in tablets, human urine, and plasma by capillary electrophoresis using maltodextrin as the chiral selector.

The stereoselective analysis and separation of racemic drugs play an important role in pharmaceutical industry to eliminate the unwanted isomer and find the right therapeutic control for the patient. Present study suggests a maltodextrin-modified capillary electrophoresis method for a single-run chiral separation of two closely similar opiate pain relief drugs: tramadol (TRA) and methadone (MET). The best separation method possible for the both enantiomers was achieved on an uncoated fused-silica capillary at 25°C using 100 mM phosphate buffer (pH 8.0) containing 20% (w v-1 ) maltodextrin with dextrose equivalent of 4-7 and an applied voltage of 16 kV. Under optimal conditions, the baseline resolution of TRA and MET enantiomers was obtained in less than 12 minutes. The relative standard deviations (n = 3) of 20 µg mL-1 TRA and MET were 2.28% and 3.77%, respectively. The detection limits were found to be 2 µg mL-1 for TRA and 1.5 µg mL-1 for MET. This method was successfully applied to the measurement of drugs concentration in their tablets, urine, and plasma samples.

Development of a modified partial filling method in capillary electrophoresis using two chiral plugs for the simultaneous enantioseparation of chiral drugs: Comparison with mixed chiral selector capillary electrophoresis.

In this study, a chiral CE method was developed based on the partial filling technique with two chiral plugs for the simultaneous enantioseparation of some racemic drugs, including baclofen, carvedilol, cetirizine, chlorpheniramine, citalopram, fluoxetine, hydroxyzine, propranolol, tramadol, trihexyphenidyl. This method of capillary filling involves the application of two adjacent chiral plugs containing the same BGE, but with different chiral selectors in the plugs for the enantioseparation of a mixture of drugs which cannot be separated with single or mixed chiral selectors. By using this method, each plug can separate the enantiomers independently (same as a single chiral selector modified CE) and the possible interactions between the chiral selectors would be inhibited. The best results were obtained using a fused silica capillary (60cm×50µm id (50cm effective length)) with phosphate buffer (100mM, pH 3.0) containing 10mM hydroxypropyl-α/ß-cyclodextrin and 10% (w/v) maltodextrin and detected by UV at 214nm. The influence of the length and order of the chiral plugs on the enantioresolution was also studied and optimized. The proposed method was compared with a mixed chiral selector-CE system with a combination of hydroxypropyl-α-cyclodextrin/hydroxypropyl-ß-cyclodextrin and maltodextrin in the BGE. According to the results, the modified partial filling method is a simple and efficient method for the simultaneous chiral separation and offers appropriate migration times and resolutions compared to the results obtained from mixed chiral selector CE.

Evaluation of the synergistic effect with amino acids for enantioseparation of basic drugs using capillary electrophoresis.

The synergistic effect of two acidic amino acids, aspartic and glutamic acid, on the electrophoretic enantioseparation of four basic drugs was evaluated in the BGE containing a CD and at different pHs. Chlorpheniramine, hydroxyzine, propranolol and tramadol were used as the basic model drugs. However, no enantioseparations were achieved with a BGE containing sole amino acid, but the combined use of an acidic amino acid and a CD showed improved enantioseparations (synergistic effect) compared with the single CD system. The results demonstrated that at optimized pH, the electrostatic interactions of the anionic amino acids with the positively charged basic drugs could result in a decrease of the analyte migration velocity and it consequently improved the enantioseparation. The effective parameters such as the amino acid and chiral selector type and concentration, buffer pH, applied voltage, and capillary temperature were optimized. Favorable enantiomeric resolution and migration times of the model drugs were achieved with a 100 mM phosphate buffer solution (pH 3.0) containing 5.0 mM HP-α-CD/HP-ß-CD and 20 mM aspartic acid with an 18 kV applied voltage at 25°C. 1 H NMR experiments were also carried out in a mixture of an analyte and CD in the absence and presence of aspartic acid. The NMR results were consistent with the results obtained by CE which showed the synergistic effect of amino acid.

Surfactant-assisted electromembrane extraction combined with cyclodextrin-modified capillary electrophoresis for the separation and quantification of Tranylcypromine enantiomers in biological samples.

Surfactant-assisted electromembrane extraction coupled with cyclodextrin-modified capillary electrophoresis was developed for the separation and determination of Tranylcypromine enantiomers in biological samples. This combination would provide a new strategy for selective and sensitive determination of target analytes. The addition of surfactant in the donor solution improved the analyte transport into the lumen of hollow fiber that resulted in an enhancement in the analytes migration into acceptor solution. Optimization of the variables, affecting proposed method, was carried out and best results were achieved with a 175 V potential as driving force of the electromembrane extraction, 2-nitrophenyloctylether as the supported liquid membrane, donor solution containing 0.2 mM Triton X-100 with pH 3 and 0.1 M HCl for acceptor solution. Then, the extract was analyzed using cyclodextrin-modified capillary electrophoresis method for separation of Tranylcypromine enantiomers. The best results were obtained with a phosphate running buffer (100 mM, pH 2.0) containing 7% w/v hydroxypropyl-α-cyclodextrin. Under the optimum conditions, a low limit of detection (3.03 ng/mL), good linearity (R2  > 0.9953), and relative standard deviations below 4.0% (n = 5) were obtained. Finally, this procedure was applied to determine the concentration of Tranylcypromine enantiomers in urine samples with satisfactory results.

All-in-one solid-phase microextraction: Development of a selective solid-phase microextraction fiber assembly for the simultaneous and efficient extraction of analytes with different polarities.

In the present work, for the first time, an all-in-one solid-phase microextraction technique was developed for the simultaneous and efficient extraction of analytes within a vast polarity range. A novel fiber assembly composed of two different steel components each coated with different coatings (polydimethylsiloxane and polyethylene glycol) in terms of polarity by sol-gel technology was employed for the extraction of model compounds of different polarity in a single run followed by gas chromatography with mass spectrometry. Effective parameters in the extraction step and gas chromatography with mass spectrometry analysis were optimized for all model compounds. The detection limits of the developed method for model compounds were below 0.2 ng/L. The repeatability and reproducibility of the proposed method, explained by relative standard deviation, varied between 7.22 and 9.15% and between 7.95 and 14.90 (n = 5), respectively. Results showed that, under random conditions, compared to separate extractions performed by two other differently end-coated components that had not been assembled as the final dual fiber, as two individual fibers; simultaneous, efficient and relatively selective extraction of all model compounds was obtained in a single run by the proposed all-in-one technique. Finally, the optimized procedure was applied to extraction and determination of the model compounds in spiked water samples.

Surfactant-assisted electromembrane extraction combined with capillary electrophoresis as a novel technique for the determination of acidic drugs in biological fluids.

In this paper, for the first time, surfactant-assisted electromembrane extraction coupled with capillary electrophoresis with UV detector was introduced for the extraction of acidic drugs from biological fluids. In this technique, in the presence of the nonionic surfactant in the donor phase, tendency of analyte ions into the supported liquid membrane (SLM) was increased. Naproxen and diclofenac were selected as model acidic drugs. In order to obtain the best extraction efficiency, several factors influencing the extraction efficiency were investigated. Optimal extractions were accomplished with 1-octanol as the SLM, 15 Volt dc potential as the driving force, pH 12 in acceptor solution, and 0.2 mmol/L Triton X-100 with pH 7.4 in donor solution. Equilibrium extraction conditions were obtained after 15 min of operation where the whole assembly agitated at 1000 rpm. Under the optimized conditions, preconcentration factors in the range of 176-184 and recoveries in the range of 88-92% were obtained. The applied method offers acceptable linearity with correlation coefficients higher than 0.9992. Limits of detection of 1.51 ng/mL and 2.42 ng/mL were obtained for naproxen and diclofenac, respectively. Finally, the developed method was successfully applied for the determination of naproxen and diclofenac in different matrices including plasma and urine samples.