Determination Of Non-steroidal Anti-inflammatory Drugs Research Articles

A high-throughput sample preparation approach for the determination of nonsteroidal anti-inflammatory drugs in urine samples through membrane-based microextraction employing a green supramolecular solvent

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of drugs with antipyretic, analgesic, and anti-inflammatory effects widely used worldwide. This study aimed at developing an environmentally friendly and high-throughput sample preparation method for the determination of six NSAIDs in urine samples followed by high-performance liquid chromatography coupled to diode-array detection (HPLC-DAD). The experimental workflow consisted of hollow-fiber microporous membrane liquid-liquid extraction (HF-MMLLE) using a supramolecular solvent immobilized into the porous of polypropylene hollow membranes (1 cm length). These membranes were attached to a 96-well plate system to permit multiple extractions simultaneously. Under the optimized conditions, limits of detection (LODs) and limits of quantification (LOQs) ranged from 6.06 to 30.3 µg/L and from 20 to 100 µg/L, respectively. The linear ranges varied from 20 to 1000 µg/L for indomethacin and diclofenac, from 50 to 1000 µg/L for ketoprofen and ibuprofen, and from 100 to 1000 µg/L for naproxen and fenoprofen. The coefficients of determination (R²) ranged from 0.9735 to 0.9997. Intraday precision ranged from 6.13 to 20.11 %, interday precision varied from 2.87 to 20.72 %, and accuracy ranged from 92.49 to 126.89 %. Moreover, the recently proposed Sample Preparation Metric of Sustainability (SPMS) was employed to evaluate the greenness of the sample preparation technique resulting in a score of 8.0, which is highly satisfactory according to the concepts of green analytical chemistry.

Fast and efficient extraction and determination of nonsteroidal anti-inflammatory drugs using poly(8-hydroxyquinoline)-coated magnetic graphene oxide nanocomposite prior to capillary electrophoresis analysis in wastewater, breast milk, and urine samples.

In this study, magnetic graphene oxide coated with poly(8-hydroxyquinoline) was successfully synthesized, characterized, and utilized as a novel sorbent for the ultrasonic-assisted dispersive magnetic solid-phase extraction of naproxen and ibuprofen. These analytes served as representative analytes for two nonsteroidal anti-inflammatory drugs in various real samples. Characterization techniques, such as IR, X-ray powder diffraction, field emission scanning electron microscopy, energy-dispersive X-ray-mapping, and Brunauer-Emmett-Teller (BET), were used to confirm the correctness synthesis and preparation of the nanocomposites. Effective parameters on the extraction efficiency were investigated to maximize the analytical performance of the developed method. The dynamic range (1-1000µgL-1), coefficients of determination (R2≥0.997), the limits of detection (0.3-1.0µgL-1), and limit of quantification (1.0-3.0µgL-1), intra-day and inter-day precisions (3.5%-7.2%) were achieved. The method validation results showed extraction recovery ranging from 80.4% to 96.0% and preconcentration factors ranging from 137 to 140.

EVALUATION OF GREENNESS PROFILES OF VARIOUS DEVELOPED METHODS FOR THE DETERMINATION OF COMMONLY USED NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs) IN ENVIRONMENTAL WATERS

Objective: In our study, it was aimed to make a comparative analysis of the environmental impact profiles of two approaches including Gas Chromatography (GC) and Liquid Chromatography (LC) methods, which are frequently used techniques for the determination of non-steroidal anti-inflammatory drugs (NSAIDs) and their metabolites in environmental water samples. Material and Method: The evaluation of the methods' environmental impact was performed using National Environmental Methods Index Label (NEMI), Analytical Eco-scale, Analytical GREEnness Metric (AGREE), and Green Analytical Procedure Index (GAPI). Result and Discussion: The routine analysis of NSAIDs in environmental waters is carried out, resulting in a significant volume of chemical waste. In recent times, there has been a growing significance attributed to environmentally conscious analytical methodologies and the evaluation of methodologies through a green lens to confront this challenge. There is no statistically significant difference in terms of environmental impact profile was observed between the two methods compared.

Solar energy-based electromembrane extraction using agarose gel for the determination of nonsteroidal anti-inflammatory drugs from biological samples: An environmentally friendly strategy

This paper presents the application of solar energy as a renewable resource in gel electromembrane extraction (G-EME). The extraction driving force (electrical field) generated from solar energy is stored through photovoltaic panels and significantly contributes to reducing the emission of greenhouse gasses. Moreover, the replacement of the polypropylene membrane and organic extracting solvents with biodegradable agarose membrane and the aqueous extracting solutions makes the presented approach compatible with the principles of green chemistry. Naproxen (NAP) and ibuprofen (IBF) were extracted from urine samples to the aqueous acceptor phase containing an anode electrode situated on the other side of the agarose gel membrane. Acceptable linearity was obtained in the concentration ranges of 6–100 and 9–100 μg. L − 1 with detection limits of 2 and 3 μg. L − 1 for NAP and IBF, respectively.

Study the Effect of Zwitterionic Hydrophilic Interaction for Simultaneous Determination of Non-Steroidal Anti-Inflammatory Drugs in Dosage Forms

Flurbiprofen and ketorolac are non-steroidal anti-inflammatory drugs (NSAIDs) that include both hydrophilic and hydrophobic functional groups in their structures. By connecting sulfobetaine molecules to polystyrene-divinylbenzene particles, two ZIC-HILIC stationary phases (ZIC-SB1 and ZIC-SB4) were developed for chromatographic separation of NSAIDs with varying chain lengths using Ultraviolet as detection. The different chain lengths of the stationary phases are utilized to investigate the retention behaviour of NSAIDs. Simultaneous quantification methods for ZIC-HILIC were developed. Flurbiprofen and ketorolac exhibited high precision with a small relative standard deviation (RSD) value of 0.48%, linear ranges of 0.015-6 and 0.06-4.5 ppm and detection limits of 0.009-0.006 and 0.01-0.008 ppm with a coefficient of determination (R2) of 0.9995-0.9997 for the ZIC-SB1 and ZIC-SB4 stationary phases, respectively. Statistical testing was used to compare the approaches to the British Pharmacopoeia protocol, and no difference in accuracy was discovered.

Efficient determination of non-steroidal anti-inflammatory drugs by micellar electrokinetic chromatography in wastewater.

Recently, non-steroidal anti-inflammatory drugs (NSAIDs) have been increasingly used in humans and animals. Despite being effective against a wide variety of diseases, they pose a threat to aquatic environments. In the current work, a highly efficient, selective, and sensitive micellar electrokinetic chromatography (MEKC) method was developed for the determination of five NSAIDs in environmental water samples. The optimal separation BGE was 15 mM borate buffer (pH 9), 90 mM SDS, and 10% methanol at a separation voltage of 15 kV and a hydrodynamic injection of 10 mbar for 5 s. The results presented in this study provide a higher number of theoretical plates N > 780 000 with excellent RSDs of 0.1-1.5% and great sensitivity (3-15 μg L-1) for NSAIDs. To validate this method, the solid phase extraction method was optimized using two different cartridges (C18 and Oasis HLB); the results showed excellent recoveries (73-111.6%) for all the analytes in wastewater samples.

A Facile and in situ Preparation Technique for Solid-Phase Microextraction Fibers with MOFs Coating

In this study, a facile preparation technique for in situ growth of MOFs-based-coated solid-phase microextraction (SPME) fibers is proposed. NH2-MIL-53 can be grown on the Al wire simply by immersing the Al wire in the solution of growth seeds and metal–organic frameworks (MOFs) successively, thereby obtaining the SPME fiber. The as-prepared fiber was combined with gas chromatography flame ionization detection (GC-FID) for the determination of non-steroidal anti-inflammatory drugs (NSAIDs) in water samples. Compared with NH2-MIL-53-coated fiber prepared with the gluing method, MIL-53-coated fiber prepared by in situ self-growth and commercial polyacrylate (PA) fiber, the as-prepared fiber demonstrated the better extraction performance, owing to more exposed adsorption sites and stronger interactions with the target. Moreover, the fiber exhibited a long service life due to multifaceted stability. After optimization of extraction and desorption conditions, the analytical method had a low-detection limit (0.002–0.05[Formula: see text][Formula: see text]g[Formula: see text]L[Formula: see text], a wide linear range (0.01–500[Formula: see text][Formula: see text]g[Formula: see text]L[Formula: see text] and good reproducibility (relative standard deviation [Formula: see text]5.84%) and provided good results for actual water samples. MOFs-based SPME fibers grown on metal wires using a facile in situ technique can maximize the extraction advantage of MOFs coating, which well promotes the application and development of MOFs in solid-phase microextraction technology.

Rapid Determination of Non-Steroidal Anti-Inflammatory Drugs in Urine Samples after In-Matrix Derivatization and Fabric Phase Sorptive Extraction-Gas Chromatography-Mass Spectrometry Analysis.

Fabric phase sorptive extraction (FPSE) has become a popular sorptive-based microextraction technique for the rapid analysis of a wide variety of analytes in complex matrices. The present study describes a simple and green analytical protocol based on in-matrix methyl chloroformate (MCF) derivatization of non-steroidal anti-inflammatory (NSAID) drugs in urine samples followed by FPSE and gas chromatography-mass spectrometry (GC-MS) analysis. Use of MCF as derivatizing reagent saves substantial amounts of time, reagent and energy, and can be directly performed in aqueous samples without any sample pre-treatment. The derivatized analytes were extracted using sol-gel Carbowax 20M coated FPSE membrane and eluted in 0.5 mL of MeOH for GC-MS analysis. A chemometric design of experiment-based approach was utilized comprising a Placket-Burman design (PBD) and central composite design (CCD) for screening and optimization of significant variables of derivatization and FPSE protocol, respectively. Under optimized conditions, the proposed FPSE-GC-MS method exhibited good linearity in the range of 0.1-10 µg mL-1 with coefficients of determination (R2) in the range of 0.998-0.999. The intra-day and inter-day precisions for the proposed method were lower than <7% and <10%, respectively. The developed method has been successfully applied to the determination of NSAIDs in urine samples of patients under their medication. Finally, the green character of the proposed method was evaluated using ComplexGAPI tool. The proposed method will pave the way for simper analysis of polar drugs by FPSE-GC-MS.

A SPE/LC–MS Method for the Simultaneous Determination of Non-Steroidal Anti-Inflammatory Drugs Using TiO2 Nanotubes Coated with Cetyltrimethylammonium Bromide as Adsorbent

A SPE/LC–MS Method for the Simultaneous Determination of Non-Steroidal Anti-Inflammatory Drugs Using TiO2 Nanotubes Coated with Cetyltrimethylammonium Bromide as Adsorbent

Ultra fast liquid chromatographic analysis of nonsteroidal anti-inflammatory drugs with fluorimetric detection in tap water, urine, and pharmaceutical samples

ABSTRACT A novel analytical method based on ultra-fast liquid chromatography using fluorimetric detector was developed and validated for determination of non-steroidal anti-inflammatory drugs (NSAIDs) (ibuprofen (IBP), etodolac (ETD), dexketoprofen (DKP), sodium diclofenac (SDCF), and naproxen (NPX) in tap water, urine and pharmaceutical samples. Precolumn derivatisation of targeted NSAIDs was carried out with 4-bromomethyl-7-methoxy coumarin (BrMmC) using dibenzo-18-crown-6-ether as reaction catalyst leading to the formation of a fluorescent compound. The obtained fluorescent compound of NSAIDs were measured at excitation wavelength as 325 nm, and emission wavelength of 395 nm. Optimum analytical conditions were carefully studied and improved. C18 column, with the dimensions of 4.0 × 100 mm and 3 µm particle size, was used. Gradient elution with methanol: water 40:60; v/v (eluent A) and acetonitrile 100% (eluent B) were used as mobile phase and flow rate of 0.4 mL/min. The linearity range of the analytes were between 0.01–10.0 µg mL−1. Recovery values obtained from pharmaceutical preparations were found as 100.04%, 99.99%, 100.09%, 99.98% and 100.47% for IBP, ETO, DKP, SDCF, NPX, respectively. LOD values were found to vary between 0.00009 µg mL−1 and 0.00048 µg mL−1 in tap water, urine and pharmaceutical samples. The optimised technique was successfully applied for the determination of NSAIDs in tap water, urine, and pharmaceutical specimen. The specified NSAIDs were not found in real tap water samples.

Introduction of a Zn-based metal\u2013organic framework @ biomass porous activated carbon as a high-sensitive coating for a stainless steel SPME fiber: application to the simultaneous analysis of nonsteroidal anti-inflammatory drugs

The present study introduces a high-efficiency nanocomposite material featuring a zinc-based metal–organic framework and a novel porous activated carbon derived from bread waste. The prepared nanocomposite, namely Zn-MOF-5@BHPAC, has been synthesized by a low-temperature hydrothermal process and coated onto the surface of a stainless steel wire with epoxy glue. The fabricated fiber has been employed as an SPME fiber applied in the extraction and pre-concentration of some nonsteroidal anti-inflammatory drugs (NSAIDs) before their high-performance liquid chromatography-ultraviolet (HPLC-UV) studies. The characterization studies were performed utilizing field emission scanning electron microscopy, elemental mapping, energy-dispersive X-ray spectroscopy, elemental analyzer, Fourier-transform infrared spectroscopy, and Brunauer–Emmett–Teller surface area analysis. Under the optimal conditions, the method demonstrated low detection limits (LODs, 0.06–0.15 µg L–1), wide linear ranges (LRs, 0.20–380 µg L–1) with good linearity (R2 > 0.991), good precisions (RSDs < 6.95%), and acceptable relative recoveries (RR > 85%). Using the green and affordable biomass of bread as a novel carbon-rich source is an innovative idea provided in this study. In addition, the hybridization of the obtained carbon-based material with the MOF compound to create a new high-capacity sorbent is another strength of the proposed method. Long service lifetime, economic efficiency, environmental friendliness, and high extraction capability were some of the other advantages of the suggested procedure. Therefore, the method can utilize successfully for the simultaneous determination of NSAIDs (as model analytes) in different matrixes.

Lab-In-Syringe with Bead Injection Coupled Online to High-Performance Liquid Chromatography as Versatile Tool for Determination of Nonsteroidal Anti-Inflammatory Drugs in Surface Waters

We report on the hyphenation of the modern flow techniques Lab-In-Syringe and Lab-On-Valve for automated sample preparation coupled online with high-performance liquid chromatography. Adopting the bead injection concept on the Lab-On-Valve platform, the on-demand, renewable, solid-phase extraction of five nonsteroidal anti-inflammatory drugs, namely ketoprofen, naproxen, flurbiprofen, diclofenac, and ibuprofen, was carried out as a proof-of-concept. In-syringe mixing of the sample with buffer and standards allowed straightforward pre-load sample modification for the preconcentration of large sample volumes. Packing of ca. 4.4 mg microSPE columns from Oasis HLB® sorbent slurry was performed for each sample analysis using a simple microcolumn adapted to the Lab-On-Valve manifold to achieve low backpressure during loading. Eluted analytes were injected into online coupled HPLC with subsequent separation on a Symmetry C18 column in isocratic mode. The optimized method was highly reproducible, with RSD values of 3.2% to 7.6% on 20 µg L−1 level. Linearity was confirmed up to 200 µg L−1 and LOD values were between 0.06 and 1.98 µg L−1. Recovery factors between 91 and 109% were obtained in the analysis of spiked surface water samples.

Potential of microchip electrophoresis in pharmaceutical analysis: Development of a universal method for frequently prescribed nonsteroidal anti-inflammatory drugs

A novel microchip electrophoresis method with conductivity detection for the determination of nonsteroidal anti-inflammatory drugs (NSAIDs) in several pharmaceutical formulations was developed. The three frequently used NSAIDs – acetylsalicylic acid, diclofenac and ibuprofen were baseline separated on a poly(methyl methacrylate) microchip with coupled separation channels. Elimination of matrix components such as excipients, was realized through online combination of isotachophoresis (ITP) with zone electrophoresis (ZE). ITP-ZE hyphenation can also facilitate preconcentration of target analytes. ITP was carried out in the first separation channel at pH 6.5, while the second channel of the microchip was used for ZE separation and detection of the analytes at pH 7.0. The developed ITP-ZE method was demonstrated to be applicable for direct and reliable determination of NSAIDs in eleven pharmaceutical formulations. The noticeable advantage of this approach is that only simple sample pretreatment (filtration and dilution) is necessary. The method performance parameters, such as linearity (20–250% of nominal concentration of studied NSAIDs in the test samples), accuracy (98–102%) and precision (less than 2% RSD) were obtained. This universal approach is suitable for the determination of frequently used NSAIDs in a single analysis in less than 15 min. In addition to simple sample pretreatment, low running costs and minimal environmental impact could make this method attractive for the analysis of pharmaceutical preparations.

Microstructured optical fibers sensor modified by deep eutectic solvent: Liquid-phase microextraction and detection in one analytical device

A sensitive optical sensor based on hollow core microstructure optical fibers modified with deep eutectic solvent was produced for the first time. An easy procedure for the modification of hollow-core microstructure optical fibers with deep eutectic solvent was developed. Deep eutectic solvents based on natural monoterpenoids and fatty acids were investigated for glass surface modification. The sensor was used for the determination of non-steroidal anti-inflammatory drugs (mefenamic acid, diclofenac, flurbiprofen and ketoprofen) in human urine samples. The mechanism of the sensor response was investigated and discussed. Liquid-phase microextraction of non-steroidal anti-inflammatory drugs was implemented in deep eutectic solvent phase supported in the inner surface of hollow-core microstructure optical fibers followed by transmission spectra measurement in one analytical device. The preconcentration step performed directly in the analytical device allowed to obtain high sensitivity and selectivity. The limits of detection calculated from the calibration plots based on 3σ were 3 μg L−1 for all target analytes.

Restricted access supramolecular solvent based magnetic solvent bar liquid-phase microextraction for determination of non-steroidal anti-inflammatory drugs in human serum coupled with high performance liquid chromatography-tandem mass spectrometry

A hexafluroisopropanol (HFIP)-alkanol supramolecular solvent (SUPRAS) based magnetic solvent bar (MSB) liquid-phase microextraction (LPME) method was proposed for extraction of non-steroidal anti-inflammatory drugs (NSAIDs, including ketoprofen, naproxen, indomethacin and diclofenac) in human serum. The restricted access HFIP-alkanol SUPRAS was prepared by injecting a mixture of HFIP and alkanol into water. A stainless-steel needle was inserted into a piece of hollow fiber to prepare a magnetic bar. Then the magnetic bar was dipped in SUPRAS to impregnate the wall pores of the hollow fiber, followed by placing it into the serum sample for extraction. Only 4 μL of SUPRAS was consumed per bar. The MSB not only functioned for stirring, but also played the role of extraction and magnetic separation. Under the optimal extraction conditions (seven MSBs, extraction time 33 min and stirring rate 730 rpm), which was obtained by one variable-at-a-time and response surface methodology, the novel MSB-LPME was coupled with high performance liquid chromatography-tandem mass spectrometry to determine NSAIDs in human serum. The method showed a good linear relationship (correlation coefficients ≥ 0.9939). Method limits of detection and method limits of quantitation were in the range of 0.25-0.95 μg L-1 and 0.83-3.16 μg L-1, respectively. The recoveries for the spiked human serum samples ranged from 86.8% to 125.1% with intra- and inter-day relative standard deviations less than 9.2% and 18.1%, respectively. Moreover, the method did not require a protein precipitation step, and matrix effects of 72.8%-117.7% showed little interference with mass spectrometry detection, which was due to the double cleanup provided by the restricted access property of SUPRAS and the filtration capacity of hollow fiber. The HFIP-alkanol SUPRAS-based MSB-LPME method proved to be simple, highly efficient and environment-friendly for the pretreatment of serum/plasma.

Dispersive micro-solid phase extraction combined with switchable hydrophilicity solvent-based homogeneous liquid-liquid microextraction for enrichment of non‐steroidal anti‐inflammatory drugs in environmental water samples

Herein, a sensitive and green method combining dispersive micro-solid phase extraction (D-μ-SPE) and homogeneous liquid-liquid microextraction (HLLME) has been developed. Magnetic layered double hydroxide nanoparticals were prepared and used as adsorbents in d-μ-SPE. The fascinating dissolvable characteristic of the material can eliminate elution step without usage of toxic organic solvents. Dipropylamine was used as a pH-triggered switchable hydrophilicity solvent that can change the miscible/immiscible states reversibly, achieving fast two-phase separation. To demonstrate the applicability of proposed method, three non-steroidal anti-inflammatory drugs including ketoprofen, naproxen and tolmetin in water samples were enriched and purified prior to HPLC-UV analysis. The influencing parameters such as pH of sample solution, amount of sorbent, vortex time, type and volume of acidic solution and SHS, volume of NaOH were optimized in detail. The method exhibits good linearity (0.1–50 ng/mL), low limits of detection (0.02–0.05 ng/mL), high precision (RSDs<9.3%) and acceptable accuracy (97.2%-105.7%). Therefore, the presented procedure is fast, sensitive, simple and suitable for determination of non-steroidal anti-inflammatory drugs from aqueous matrices.

In-tube stir bar sorptive extraction based on 3-aminopropyl triethoxysilane surface-modified Ce-doped ZnAl layered double hydroxide thin film for determination of nonsteroidal anti-inflammatory drugs in saliva samples

Athin-film based on 3-aminopropyl triethoxysilane surface-modified Ce-doped zinc-aluminum layered double hydroxide was synthesized on the inner surface of an aluminum tube. It has beenapplied toin-tube stir bar sorptive extraction of nonsteroidal anti-inflammatory drugs in saliva samples followed by high-performance liquid chromatography. The sorbent was characterized by scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and elemental mapping. The extraction parameters including sample pH (4.2), extraction time (10min), stirring speed (800rpm), type of eluent (acidified tetrahydrofuran), eluent volume (100μL), and desorption time (6min) were thoroughly optimized. Under the optimum conditions, limits of detection were found to be less than 5.0ngmL-1. Calibration plots were linear within the range 10-1000ngmL-1 (R2 > 0.9982). Absolute recoveries were calculated in the range 63.5 to 72.4%. The repeatability (intra- and inter-day precision) and reproducibility (tube-to-tube precision) at concentrations of 50, 250, and 500ngmL-1 were less than 7.6% and 9.4%, respectively. The method accuracy based on the relative error was calculated at these concentrations and ranged from - 4.9 to - 9.3% for intra-day relative error (%) and - 6.8 to - 11% for inter-day relative error (%). Finally, the method applicability was examined for the determination of nonsteroidal anti-inflammatory drugs in saliva samples, and good relative recoveries were obtained within the range 86.5 to 95.2%. As a result, the introduced method can be applied as a suitable alternative to measuring nonsteroidal anti-inflammatory drugs in biological fluids. Graphical abstract A surface-modified Ce-doped ZnAl LDH thin film was synthesized on the inner surface of an Al tube and applied for in-tube stir bar sorptive extraction of NSAIDs in saliva.

Determination of Non-Steroidal Anti-Inflammatory Drugs in Animal Urine Samples by Ultrasound Vortex-Assisted Dispersive Liquid–Liquid Microextraction and Gas Chromatography Coupled to Ion Trap-Mass Spectrometry

A low solvent consumption method for the determination of non-steroidal anti-inflammatory drugs (NSAIDs) in animal urine samples is studied. The NSAIDs were extracted with CH2Cl2 by the ultrasound vortex assisted dispersive liquid–liquid microextraction (USVA-DLLME) method from urine samples, previously treated with β-glucuronidase/acrylsulfatase. After centrifugation, the bottom phase of the chlorinated solvent was separated from the liquid matrix, dried with Na2SO4, and derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) + trimethylchlorosilane (TMCS) (99 + 1). After cooling at room temperature, the solution was concentrated under nitrogen flow, and 1 µL of solution was analyzed in gas chromatography/ion trap-mass spectrometry (GC-IT-MS). The enrichment factor was about 300–450 times and recoveries ranged from 94.1 to 101.2% with a relative standard deviation (RSD) of ≤4.1%. The USVA-DLLME process efficiency was not influenced by the characteristics of the real urine matrix; therefore, the analytical method characteristics were evaluated in the range 1–100 ng mL−1 (R2 ≥ 0.9950). The limits of detection (LODs) and limits of quantification (LOQs) were between 0.1 and 0.2 ng mL−1 with RSD ≤4.5% and between 4.1 and 4.7 ng mL−1 with RSD ≤3.5%, respectively, whereas inter- and intra-day precision was 3.8% and 4.5%, respectively. The proposed analytical method is reproducible, sensitive, and simple.

New and sensitive spectrofluorimetric method for the determination of non-steroidal anti inflammatory drugs, etodolac and diclofenac sodium in pharmaceutical preparations through derivatization with 7-fluoro-4-nitrobenzo-2- oxa-1,3-diazole

A rapid, accurate and sensitive method was developed and validated for the determination of non-steroidal anti-inflammatory drugs, etodolac and diclofenac sodium in pharmaceutical preparations. The proposed method was based on the reaction of these drugs with 7-fluoro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-F) in buffer of pH 8.5 to yield a yellow, fluorescent product. The method was validated for specificity, linearity, limit of detection, limit of quantification, precision, accuracy, recovery and robustness. Beer's law is obeyed over the concentration range of 40-600 ng/mL for etodolac, 25-500 ng/mL for diclofenac sodium, respectively. The detection limits were found to be 0.071 ng/mL for etodolac, 0.055 ng/mL for diclofenac sodium, respectively. Statistical analysis of the results has been carried out revealing high accuracy and good precision. The proposed methods were successfully applied for the determination of the drugs in their pharmaceutical preparations with good recoveries. The developed methods were sensitive, accurate and simple. The results obtained by the proposed method were comparable with those obtained by the official method.

One-step hydrothermal synthesis of magnetic nitrogen-doped graphene for magnetic solid-phase extraction of nonsteroidal anti-inflammatory drugs in environmental water samples.

Graphene oxide has received extensive attention because of its unique properties and potential applications. In this study, magnetic nitrogen-doped graphene was prepared by one-step hydrothermal reaction using urea as the dopant and reductant, and ferroferric oxide nanoparticles were in situ deposited on the surface of the nanohybrids. The magnetic nitrogen-doped graphene was characterized using various physical and chemical methods. It was used as a new adsorbent for the magnetic solid-phase extraction of four nonsteroidal anti-inflammatory drugs from the river water. The parameters influencing the extraction efficiency were optimized in detail. Under optimal conditions, this method provided a wide linear range (5-200 ng/mL). The limits of detection were in the range of 1.07-5.10 ng/mL. The recoveries varied from 81.2 to 121.5% with relative standard deviations of less than 10.8%. Overall, we can conclude that the proposed method offers an efficient pretreatment and enrichment and can be successfully applied for the extraction and determination of nonsteroidal anti-inflammatory drugs in complex matrices.