Computer aided-molecular design and synthesis of a high selective molecularly imprinted polymer for solid-phase extraction of furosemide from human plasma

Highly selective molecularly imprinted polymers (MIPs) for solid-phase extraction and determination of furosemide in human plasma have been designed and prepared. In order to study the intermolecular interactions in the pre-polymerization mixture and to find a suitable functional monomer in MIP preparation, a computational approach was developed. It was based on the comparison of the binding energy of the complexes between the template and functional monomers. Having confirmed the results of computational method, three MIPs were synthesized with different functional monomers, i.e. acrylamide (AAM), 4-vinylpiridine (4-VP) and acrylonitrile (ACN), and then evaluated using Langmuir-Freundlich (LF) isotherm. Using the MIP prepared by AAM as functional monomer, a molecularly imprinted solid-phase extraction procedure followed by high performance liquid chromatography with ultraviolet detector (MISPE-HPLC-UV) was developed for selective extraction and determination of furosemide in human plasma. For the proposed MISPE-HPLC-UV method, the linearity between responses (peak area) and concentration was found over the range of 75-3500 ng mL⁻¹ with a linear regression coefficient (R²) of 0.997. The limit of detection (LOD) and quantification (LOQ) in plasma were 12.9 and 43.3 ng mL⁻¹, respectively.     

Development of a highly sensitive and selective hyphenated technique (molecularly imprinted micro-solid phase extraction fiber-molecularly imprinted polymer fiber sensor) for ultratrace analysis of folic acid

A simple polymerization strategy is reported in this work which allows molecularly imprinted polymeric fiber (monolith) fabrication for direct use in sensing devices. This is advantageous for achieving higher degree of enrichment of target analyte (folic acid) from the complex matrices of real samples, without any surface fouling, cross-reactivity, and non-specific (false-positive) contributions. In order to measure serum folic acid at ultratrace level to detect spina bifida, a neural tube defect in mother, and other acute cases of proteomic diseases, the hyphenation between molecularly imprinted micro-solid phase extraction fiber and a complementary molecularly imprinted polymer-carbon composite fiber sensor has been found quite efficient. The primitive diagnosis of many chronic diseases is feasible by estimating folic acid as biomarker, with the detection limit as low as 0.0036 ng mL⁻¹ (relative standard deviation = 0.13%, signal/noise = 3) in human blood serum.     

Solid-phase molecularly imprinted pre-concentration and spectrophotometric determination of isoxicam in pharmaceuticals and human serum

A selective molecularly imprinted polymer (MIP) has been synthesized for isoxicam pre-concentration, followed by its spectrophotometric determination based on hydrogen bonding interactions between examined drug and alizarin yellow GG. This method is able to evaluate isoxicam in range of 1.0 × 10⁻³ to 20.0 μg mL⁻¹, with a limit of determination of 1.0 ng mL⁻¹. The retention capacity and pre-concentration factor of prepared sorbent are 18.5 mg g⁻¹ and 200, respectively; and the prepared MIPs can be reused at least for five times. The MIP capability for isoxicam selection and extraction from the solution is higher than non-imprinted polymer (NIP). Under optimum conditions, this procedure can be successfully applied to assay trace amounts of isoxicam in pharmaceutical and biological samples.     

Development of a group selective molecularly imprinted polymers based solid phase extraction of malachite green from fish water and fish feed samples

A group selective molecularly imprinted solid phase extraction (MISPE) for malachite green (MG) from fish water and fish feed samples was developed. Using MG as template molecule, methacrylic acid as functional monomer, ethylene glycoldimethacrylate as linking agent and bulk polymerization as synthetic method, the molecularly imprinted polymers (MIPs) were synthesized and characterized with rebinding experiment. The Scatchard polt's analysis revealed that the template-polymer system showed the two-site binding behavior with dissociation constants of 0.3194 μmol L⁻¹ and 15.70 μmol L⁻¹, respectively. MG and two structurally related compounds, leucomalachite green (LMG) and crystal violet (CV) were employed for selectivity test. The MIPs exhibited the highest selective rebinding to MG, but also displayed 83.0% and 87.5% of cross-reactivity with LMG and CV, demonstrating that MIPs could be used as group recognition sorbents in solid phase extraction. The extraction conditions of MISPE column for MG were optimized. Tap water samples spiked with MG at concentration of 0.5-10 ng mL⁻¹ were extracted by MISPE column and analyzed by high performance liquid chromatography. The recoveries of MISPE column for MG extraction were found to be 76.8-93.7% with the relative standard deviations of 2.12-10.09%, indicating the feasibility of the prepared MIPs for MG extraction. No detectable MG was observed in one fish farming water sample and two fish feed samples; while the MG concentrations in two pet fishpond water samples were found at 1.50 ng mL⁻¹ and 0.67 ng mL⁻¹, respectively.     

Ligandless-dispersive liquid-liquid microextraction of trace amount of copper ions

In the present work, a new ligandless-dispersive liquid-liquid microextraction (LL-DLLME) method has been developed for preconcentration trace amounts of copper as a prior step to its determination by flame atomic absorption spectrometry. In the proposed approach 1,2-dicholorobenzene and ethanol were used as extraction and dispersive solvents, respectively. Some factors influencing on the extraction efficiency of copper and its subsequent determination were studied and optimized, such as the extraction and dispersive solvent type and volume, pH of sample solution, extraction time and salting out effect. Under the optimal conditions, the calibration curve was linear in the range of 1.0 ng mL⁻¹-0.6 μg mL⁻¹ of copper with R² = 0.9985. Detection limit was 0.5 ng mL⁻¹ in original solution (3S_b/m) and the relative standard deviation for seven replicate determination of 0.2 μg mL⁻¹ copper was ±1.4%. The proposed method has been applied for determination of copper in standard and water samples with satisfactory results.     

A novel molecularly imprinted polymer for simultaneous extraction and determination of sudan dyes by on-line solid phase extraction and high performance liquid chromatography

A novel molecularly imprinted polymer was synthesized with attapulgite employed as matrix, which is simple and time-saving. In this method, sudan I was chosen as template molecule, 2-vinylpyridine as functional monomer and ethylene glycol dimethacrylate as cross-linking agent, respectively. The imprinted polymer was characterized by the infrared spectroscopy and transmission electron microscopy. Then the selectivity experiments were performed on sudan dyes and the recognition coefficients for sudan I, sudan II, sudan III and sudan IV were 2.9, 1.9, 1.9 and 2.3, respectively. As the packing material of solid-phase extraction, the imprinted polymer has been applied to on-line concentration of the four sudan dyes in samples from Yellow River water, tomato sauce and sausage. The corresponding analytical methods to determine these sudan dyes have been developed. The limits of detection for these sudan dyes were in the range of 0.01–0.05 ng mL⁻¹ for Yellow River water, 1.0–3.0 ng g⁻¹ for tomato sauce and 0.8–3.0 ng g⁻¹ for sausage.     

Ligandless dispersive liquid-liquid microextraction for the separation of trace amounts of silver ions in water samples and flame atomic absorption spectrometry determination

In this article, a new ligandless dispersive liquid-liquid microextraction method has been developed for preconcentration of trace quantities of silver as a prior step to its determination by flame atomic absorption spectrometry. In the proposed approach, carbon tetrachloride and ethanol were used as extraction and dispersive solvents. Several factors that may be affected on the extraction process, like, extraction solvent, disperser solvent, the volume of extraction and disperser solvent, pH of the aqueous solution and extraction time were optimized. Under the optimal conditions, the calibration curve was linear in the range of 5.0 ng mL⁻¹ to 2.0 μg mL⁻¹ of silver with R² = 0.9995 (n = 9) and detection limit based on three times the standard deviation of the blank (3S_b) was 1.2 ng mL⁻¹ in original solution. The relative standard deviation for eight replicate determination of 0.5 μg mL⁻¹ silver was ±1.5%. The high efficiency of dispersive liquid-liquid microextraction to carry out the determination of silver in complex matrices was demonstrated. The proposed method has been applied for determination of trace amount of silver in standard and water samples with satisfactory results.     

Determination of dicofol in aquatic products using molecularly imprinted solid-phase extraction coupled with GC-ECD detection

The novel molecularly imprinted microsphere (MIM) that could be applied as special sorbent was synthesized by aqueous suspension polymerization using 1,1-bis(4-chlorophenyl)-1,2,2,2-tetrachloroethane (α-chloro-DDT) as the dummy template. The obtained MIM exhibited good recognition and selectivity to dicofol and it was successfully applied as selective sorbent of solid-phase extraction for the determination of dicofol from aquatic products. At the optimum conditions of the molecularly imprinted solid-phase extraction (MISPE) coupled with GC-ECD, good linearity for dicofol was achieved in a range of 0.4-100 ng g⁻¹ (r² = 0.9995) and the recoveries at three spiked levels were ranged from 85.8% to 101.2% for aquatic products with the relative standard deviation (RSD) less than 5.6%. The presented MISPE-GC-ECD method exhibited the advantages of simplicity, selectivity and sensitivity, and could be potentially applied to the determination of dicofol in complicated aquatic products.     

Molecularly imprinted polymer microspheres prepared by Pickering emulsion polymerization for selective solid-phase extraction of eight bisphenols from human urine samples

The bisphenol A (BPA) imprinted polymer microspheres were prepared by simple Pickering emulsion polymerization. Compared to traditional bulk polymerization, both high yields of polymer and good control of particle sizes were achieved. The characterization results of scanning electron microscopy and nitrogen adsorption–desorption measurements showed that the obtained molecularly imprinted polymer microsphere (MIPMS) particles possessed regular spherical shape, narrow diameter distribution (30–60 μm), a specific surface area (S_BET) of 281.26 m² g⁻¹ and a total pore volume (V_t) of 0.459 cm³ g⁻¹. Good specific adsorption capacity for BPA was obtained in the sorption experiment and good class selectivity for BPA and its seven structural analogs (bisphenol F, bisphenol B, bisphenol E, bisphenol AF, bisphenol S, bisphenol AP and bisphenol Z) was demonstrated by the chromatographic evaluation experiment. The MIPMS as solid-phase extraction (SPE) packing material was then evaluated for extraction and clean-up of these bisphenols (BPs) from human urine samples. An accurate and sensitive analytical method based on the MIPMS-SPE coupled with HPLC-DAD has been successfully established for simultaneous determination of eight BPs from human urine samples with detection limits of 1.2–2.2 ng mL⁻¹. The recoveries of BPs for urine samples at two spiking levels (100 and 500 ng mL⁻¹ for each BP) were in the range of 81.3–106.7% with RSD values below 8.3%.     

Novel molecularly imprinted polymer prepared by nanoattapulgite as matrix for selective solid-phase extraction of diethylstilbestrol

Using nanoattapulgite as matrix, both diethylstilbestrol surface molecularly imprinted polymer and non-imprinted polymer were synthesized in this work. Compared with each other, the diethylstilbestrol surface molecularly imprinted polymer is superior to non-imprinted polymer in adsorption capacity, selectivity and mass transfer property. The maximum static adsorption capacities of diethylstilbestrol surface molecularly imprinted polymer, non-imprinted polymer and nanoattapulgite for diethylstilbestrol was 105.14, 78.54 and 28.50 mg g⁻¹, respectively. As the packing material of solid-phase extraction, the diethylstilbestrol surface molecularly imprinted polymer has been applied to concentrating diethylstilbestrol in pond water and fish samples. A corresponding analytical method to determine diethylstilbestrol has been developed. The limit of detection for diethylstilbestrol in pond water sample and fish samples were 3 μg L⁻¹ and 15 μg kg⁻¹.     

Highly selective molecular recognition and high throughput detection of melamine based on molecularly imprinted sol-gel film

Multimode reader has been generally applied in immunoassay, and in the proposed paper, the 96 well micro-plate was modified with molecularly imprinted melamine sol-gel film, based on which the highly selective and high throughput detection of melamine was achieved. Melamine was imprinted into silica sol-gel films directly using phenyltrimethoxysilane and methyltrimethoxysilane as functionalized organosilicon precursors. The binding characteristic of the imprinted film to melamine was evaluated by equilibrium binding experiments and the morphology was studied by scanning electronic microscope (SEM). Scatchard analysis was carried out to estimate the binding parameters of the imprinted film. The proposed method exhibited excellent selectivity because of specific recognition of MM by molecularly imprinted film. Under the optimum conditions, the chemiluminescence (CL) intensity had a linear relationship against the concentration of melamine over the range of 0.1-50 μg mL⁻¹ with a lower detection limit of 0.02 μg mL⁻¹.     

Development of a group-specific immunoassay for sulfonamides: Application to bee honey analysis

A set of haptens has been synthesized in order to raise generic polyclonal antibodies against sulfonamides using different strategies. After the screening of all the immunorreagents, a highly sensitive enzyme-linked immunosorbent assay was set-up for simultaneous determination of six of these antibiotics.The developed procedure allows the screening of: sulfathiazole, sulfamethoxypyridazine, sulfapyridine, sulfamethizole, sulfasalazine and N⁴-phtalylsulfathiazole with good accuracy and precision at level 0.13 ng mL⁻¹ in buffer.The suitability of developed ELISA for its application to honey analysis has been investigated. The antimicrobials were extracted from samples with acetate buffer, and cleaned up by solid phase extraction. The mean recovery found for honey samples, spiked from 1.5 to 4.5 ng mL⁻¹ equivalents of sulfathiazole (24-72 μg sulfathiazole kg⁻¹ honey), was 106%.     

Switching the selectivity of a polyglycerol dendrimer monomolecularly imprinted with d-(−)-fructose

A polyglycerol dendrimer monomolecularly imprinted with d-(−)-fructose (Fru) was synthesized. The dendrimer formed adducts with several monosaccharides, Fru, d-(+)-galactose, d-(+)-glucose, d-(+)-mannose, and methyl-α-d-mannopyranoside (MMan), by removal of four water molecules. The dendrimer preferred Fru in the absence of N,N,N′,N′-tetramethyldiaminomethane (TMDAM), whereas it preferred MMan in the presence of TMDAM.     

Flame atomic absorption spectrometry for the determination of trace amount of rhodium after separation and preconcentration onto modified multiwalled carbon nanotubes as a new solid sorbent

The present article reports on the application of modified multiwalled carbon nanotubes (MMWCNTs) as a new, easily prepared and stable solid sorbent for the preconcentration of trace rhodium ion in aqueous solution. Rhodium ions were complexed with 1-(2-pyridylazo)-2-naphthol (PAN) in the pH range of 3.2-4.7 and then the formed Rh-PAN complex was adsorbed on the oxidized MWCNTs. The adsorbed complex was eluted from MWCNTs sorbent with 5.0 mL of N,N-dimethylformamide (DMF). The rhodium in eluted solution was determined by flame atomic absorption spectrometry (FAAS). Linear range for the determination of rhodium was maintained between 0.16 ng mL⁻¹ and 25.0 μg mL⁻¹ in initial solution. Relative standard deviation for the 10 replicated determination of 4.0 μg mL⁻¹ of rhodium was ±0.97%. Detection limit was 0.010 ng mL⁻¹ in initial solution (3S_bl, n = 10) and preconcentration factor was 120. Sensitivity for 1% absorbance of rhodium (III) was 0.112 μg mL⁻¹. The sorption capacity of oxidized MWCNTs for Rh (III) was 6.6 mg g⁻¹. The effects of the experimental parameters, including the sample pH, flow rates of sample and eluent solution, eluent type, breakthrough volume and interference ions were studied for the preconcentration of Rh³⁺. The proposed method was successfully applied to the extraction and determination of rhodium in different samples.     

Ligandless-solidified floating organic drop microextraction method for the preconcentration of trace amount of cadmium in water samples

In this article, a new ligandless solidified floating organic drop microextraction (LL-SFODME) method has been developed for preconcentration of trace amount of cadmium as a prior step to its determination by flow injection-flame atomic absorption spectrometry (FI-FAAS). The methodology is based on the SFODME of cadmium with 1-dodecanol in the absence of chelating agent. Several factors affecting the microextraction efficiency, such as, pH, sodium dodecylbenzenesulfonate (SDBS) concentration, extraction time, stirring rate and temperature were investigated and optimized. Under optimized experimental conditions an enhancement factor of 205 was obtained for 100 mL of sample solution. The calibration graph was linear in the range of 1.0-25.0 ng mL⁻¹, the limit of detection (3s) was 0.21 ng mL⁻¹ and the limit of quantification (10s) was 0.62 ng mL⁻¹. The relative standard deviation (RSD) for 10 replicate measurements of 10 ng mL⁻¹ cadmium was 4.7%. The developed method was successfully applied to the extraction and determination of cadmium in standard and several water samples and satisfactory results were obtained.     

Molecularly imprinted coated graphene oxide solid-phase extraction monolithic capillary column for selective extraction and sensitive determination of phloxine B in coffee bean

A method was developed to sensitively determine phloxine B in coffee bean by molecularly imprinted polymers (MIPs) coated graphene oxide (GO) solid-phase extraction (GO-MISPE) coupled with high-performance liquid chromatography and laser-induced fluorescence detection (HPLC–LIF). The GO-MISPE capillary monolithic column was prepared by water-bath in situ polymerization, using GO as supporting material, phloxine B, methacrylic acid (MAA), and ethylene dimethacrylate (EDMA) as template, functional monomer, and cross-linker, respectively. The properties of the homemade GO-MISPE capillary monolithic column, including capacity and specificity, were investigated under optimized conditions. The GO-MIPs were characterized by scanning electron microscopy (SEM) and Fourier transform-infrared spectroscopy (FT-IR). The mean recoveries of phloxine B in coffee bean ranged from 89.5% to 91.4% and the intra-day and inter-day relative standard deviation (RSD) values all ranged from 3.6% to 4.7%. Good linearity was obtained over 0.001–2.0 μg mL⁻¹ (r = 0.9995) with the detection limit (S/N = 3) of 0.075 ng mL⁻¹. Under the selected conditions, enrichment factors of over 90-fold were obtained and extraction on the monolithic column effectively cleaned up the coffee bean matrix. The results demonstrated that the proposed GO-MISPE HPLC–LIF method can be applied to sensitively determine phloxine B in coffee bean.     

Micelle-mediated cloud point extraction and spectrophotometric determination of rhodamine B using Triton X-100

A new micelle-mediated cloud point extraction method is described for sensitive and selective determination of trace amounts of rhodamine B by spectrophotometry. The method is based on the cloud point extraction of rhodamine B from aqueous solution using Triton X-100 in acidic media. The extracted surfactant rich phase is diluted with water and its absorbance is measured at 563 nm by a spectophotometer. The effects of different operating parameters such as concentration of surfactant and salt, temperature and pH on the cloud point extraction of rhodamine B were studied in details and a set of optimum conditions were obtained. Under optimum conditions a linear calibration graph in the range of 5-550 ng mL⁻¹ of rhodamine B in the initial solution with r = 0.9991 (n = 15) was obtained. Detection limit based on three times the standard deviation of the blank (3S_b) was 1.3 ng mL⁻¹ (n = 10) and the relative standard deviation (R.S.D.) for 50 and 350 ng mL⁻¹ of rhodamine B was 2.40 and 0.87% (n = 10), respectively. The method was applied for the determination of rhodamine B in soft pastel, hand washing liquid soap, matches tip and textile dyes mixture samples.     

Phase behavior of biodegradable amphiphilic poly(l,l-lactide)-b-poly(ethylene glycol)-b-poly(l,l-lactide)

This study describes the miscibility phase behavior in two series of biodegradable triblock copolymers, poly(l-lactide)-block-poly(ethylene glycol)-block-poly(l-lactide) (PLLA-PEG-PLLA), prepared from two di-hydroxy-terminated PEG prepolymers (M_n = 4000 or 600 g mol⁻¹) with different lengths of poly(l-lactide) segments (polymerization degree, DP = 1.2-145.6). The prepared block copolymers presented wide range of molecular weights (800-25,000 g mol⁻¹) and compositions (16-80 wt.% of PEG). The copolymer multiphases coexistance and interaction were evaluated by DSC and TGA. The copolymers presented a dual stage thermal degradation and decreased thermal stability compared to PEG homopolymers. In addition, DSC analyses allowed the observation of multiphase separation; the melting temperature, T_m, of PLLA and PEG phases depended on the relative segment lengths and the only observed glass transition temperature (T_g) in copolymers indicated miscibility in the amorphous phase.     

Spectrophtometric determination of malachite green in fish farming water samples after cloud point extraction using nonionic surfactant Triton X-100

A novel and sensitive cloud point extraction procedure for the determination of trace amounts of malachite green by spectrophotometry was developed. Malachite green was extracted at pH 2.5 mediated by micelles of nonionic surfactant Triton X-100. The extracted surfactant-rich phase was diluted with ethanol and its absorbance was measured at 630 nm. The effect of different variables such as pH, Triton X-100 concentration, cloud point temperature and time and diverse ions was investigated and optimum conditions were established. The calibration graph was linear in the range of 4-500 ng mL⁻¹ of malachite green in the initial solution with r = 0.9996 (n = 10). Detection limit based on three times the standard deviation of the blank (3S_b) was 1.2 ng mL⁻¹ and the relative standard deviation (R.S.D.) for 20 and 300 ng mL⁻¹ of malachite green was 1.48 and 1.13% (n = 8), respectively. The method was applied to the determination of malachite green in different fish farming and river water samples.     

Piezoelectric quartz crystal sensor for rapid analysis of pirimicarb residues using molecularly imprinted polymers as recognition elements

A new piezoelectric quartz crystal (PQC) sensor using molecularly imprinted polymer (MIP) as sensing material has been developed for fast and onsite determination of pirimicarb in contaminated vegetables. Three MIPs particles have been prepared by conventional bulk polymerization (MIP-B) and precipitation polymerization in either acetonitrile (MIP-P1) or chloroform (MIP-P2). MIP-P2, with uniform spherical shape and mean diameter at about 50 nm, has shown the best performance as the sensing material for PQC sensor. The sensor fabricated with MIP-P2 can achieve a steady-state response within 5 min, a very short response time as compared to MIPs-coated PQC sensor reported in the literature. The sensor developed exhibits good selectivity (low response to those pesticides with similar structures to pirimicarb, such as atrazine, carbaryl, carbofuran and aldicarb) and high sensitivity to pirimicarb with a linear working range from 5.0 × 10⁻⁶ to 4.7 × 10⁻³ mol L⁻¹ (following a regression equation (r = 0.9988) of −ΔF = 0.552 + 1.79 × 10⁶ C), a repeatability (R.S.D., n = 5) of 4.3% and a detection limit (S/N = 3, n = 5) of 5 × 10⁻⁷ mol L⁻¹. The MIP-coated PQC sensor developed is shown to provide a sensitive and fast method for onsite determination of pirimicarb in aqueous extract from contaminated vegetables with satisfactory recoveries from 96 to 103% and repeatability (R.S.D., n = 5) from 4.6 to 7.1% at pirimicarb concentrations ranging from 8.0 × 10⁻⁶ to 2.0 × 10⁻⁴ mol L⁻¹.