Selective solid‐phase extraction using a molecularly imprinted polymer for the analysis of patulin in apple‐based foods

The aim of this work was to evaluate the use of a molecularly imprinted polymer as a selective solid‐phase extraction sorbent for the clean‐up and pre‐concentration of patulin from apple‐based food products. Ultra high pressure liquid chromatography coupled to ultraviolet absorbance detection was used for the analysis of patulin. The molecularly imprinted polymer was applied, for the first time, to the determination of patulin in apple juice, puree and jam samples spiked within the maximum levels specified by the European Commission No. 1881/2006. High recoveries (>77%) were obtained. The method was validated and found to be linear in the range 2–100 μg/kg with correlation coefficients greater than 0.965 and repeatability relative standard deviation below 11% in all cases. Compared with dispersive solid‐phase extraction (QuEChERS method) and octadecyl sorbent, the molecularly imprinted polymer showed higher recoveries and selectivity for patulin. The application of Affinisep molecularly imprinted polymer as a selective sorbent material for detection of patulin fulfilled the method performance criteria required by the Commission Regulation No. 401/2006, demonstrating the suitability of the technique for the control of patulin at low ppb levels in different apple‐based foods such as juice, puree and jam samples.     

Isolation of aristolochic acid I from herbal plant using molecular imprinted polymer composited ionic liquid‐based zeolitic imidazolate framework‐67

Aristolochic acid I is a toxic compound found in the genus of Aristolochia plants, which are commonly used as herbal cough treatment medicines. To remove the aristolochic acid I in extract efficiently and selectively, a molecularly imprinted polymer composed of ethylimidazole ionic liquid‐based zeolitic imidazolate framework‐67 was synthesized and used as the adsorbent. Under the conditions optimized by the software design expert, the sorbent showed highest adsorption amount of 34.25 mg/g in methanol/water (95:5, v/v) at 39°C for 138 min. The sorbent was then applied to solid phase extraction to isolate aristolochic acid I from the extract of the herbal plant Fibraurea Recisa Pierre. 0.043 mg/g of aristolochic acid I was obtained after the loading, washing, and elution processes. The limit of detection of 2.41 × 10^?5 mg/mL and good recoveries provided evidence for the accuracy of this method.     

Urinary l‐kynurenine quantification and selective extraction through a molecularly imprinted solid‐phase extraction device

l ‐Kynurenine is an endogenous metabolite generated by the catabolic pathway of l ‐tryptophan and it could be a potential biomarker to test the efficacy of several checkpoint inhibitors that have already reached the clinical trials in the antitumor therapy. Thus, a molecularly imprinted polymer specific for the recognition of this metabolite was synthesized and used as innovative system in solid‐phase extraction technique for the specific extraction and quantification of l ‐kynurenine in human urine. The off‐line system was firstly tested on l ‐kynurenine standard solutions, allowing recoveries up to 97.7% (relative standard deviation = 2.2%) and then applied to fortified and deproteinated human urine samples, where a recovery of 84.1% (relative standard deviation = 3.1%) was obtained. The method was validated and it revealed a good linearity in the range of 0.157–20 μg/mL (r² = 0.9992). The optimized procedure demonstrated a good feasibility on biological samples, allowing a ready quantification of l ‐kynurenine in the human urine, where the metabolite was found at a very low concentration (0.80 μg/mL). The extraction system developed could attract attention of pharmaceutical industries for l ‐kynurenine production as potential drug in the treatment of autoimmune disorders through its extraction and purification from biological matrixes.     

Polydopamine‐coated magnetic molecularly imprinted polymer for the selective solid‐phase extraction of cinnamic acid,ferulic acid and caffeic acid from radix scrophulariae sample

We describe novel cinnamic acid polydopamine‐coated magnetic imprinted polymers for the simultaneous selective extraction of cinnamic acid, ferulic acid and caffeic acid from radix scrophulariae sample. The novel magnetic imprinted polymers were synthesized by surface imprinting polymerization using magnetic multi‐walled carbon nanotubes as the support material, cinnamic acid as the template and dopamine as the functional monomer. The magnetic imprinted polymers were characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy and vibrating sample magnetometry. The results revealed that the magnetic imprinted polymers had outstanding magnetic properties, high adsorption capacity, selectivity and fast kinetic binding toward cinnamic acid, ferulic acid and caffeic acid. Coupled with high‐performance liquid chromatography, the extraction conditions of the magnetic imprinted polymers as a magnetic solid‐phase extraction sorbent were investigated in detail. The proposed imprinted magnetic solid phase extraction procedure has been used for the purification and enrichment of cinnamic acid, ferulic acid and caffeic acid successfully from radix scrophulariae extraction sample with recoveries of 92.4–115.0% for cinnamic acid, 89.4–103.0% for ferulic acid and 86.6–96.0% for caffeic acid.     

Recent advances and applications of molecularly imprinted polymers in solid‐phase extraction for real sample analysis

Sample pretreatment is essential for the analysis of complicated real samples due to their complex matrices and low analyte concentrations. Among all sample pretreatment methods, solid‐phase extraction is arguably the most frequently used one. However, the majority of available solid‐phase extraction adsorbents suffer from limited selectivity. Molecularly imprinted polymers are a type of tailor‐made artificial antibodies and receptors with specific recognition sites for target molecules. Using molecularly imprinted polymers instead of conventional adsorbents can greatly improve the selectivity of solid‐phase extraction, and therefore molecularly imprinted polymer‐based solid‐phase extraction has been widely applied to separation, clean up and/or preconcentration of target analytes in various kinds of real samples. In this article, after a brief introduction, the recent developments and applications of molecularly imprinted polymer‐based solid‐phase extraction for determination of different analytes in complicated real samples during the 2015‐2020 are reviewed systematically, including the solid‐phase extraction modes, molecularly imprinted adsorbent types and their preparations, and the practical applications of solid‐phase extraction to various real samples (environmental, food, biological, and pharmaceutical samples). Finally, the challenges and opportunities of using molecularly imprinted polymer‐based solid‐phase extraction for real sample analysis are discussed.     

Synthesis of molecularly imprinted polymer adsorbents for solid‐phase extraction of strobilurin fungicides from agricultural products

Molecularly imprinted polymers for strobilurin fungicides were prepared by precipitation polymerization employing azoxystrobin as template molecular together with methacrylic acid monomer and trimethylolpropane triacrylate cross‐linker. Morphological characterization showed molecularly imprinted polymers were uniform spherical particles with about 0.2 μm in diameter, while the morphologies of nonimprinted polymers were irregular bulk. The equilibrium binding and selective experiments proved that molecularly imprinted polymers possessed a higher affinity toward four fungicides compared to nonimprinted polymers and heterogeneous binding sites were found in the molecularly imprinted polymers. Molecularly imprinted solid‐phase extraction conditions, including sample loading solvents, selective washing, and elution solvents, were carefully optimized. The developed method showed good recoveries (70.0–114.0%) with relative standard deviations in range of 1.0–9.8% (n  =  3) for samples (cucumber and peach) spiked at three different levels (10, 50, and 100 μg/ kg). The detection limit (signal/noise = 3) ranged from 0.01 to 0.08 μg/kg. The results demonstrated good potential use of this convenient and highly efficient method for determining trace strobilurin fungicides in agricultural products.     

Selective solid‐phase extraction of artificial chemicals from milk samples using multiple‐template surface molecularly imprinted polymers

A novel multiple‐template surface molecularly imprinted polymer (MTMIP) was synthesized using ofloxacin and 17β‐estradiol as templates and modified monodispersed poly(glycidylmethacrylate‐co‐ethylene dimethacrylate) (P_GMA/EDMA) beads as the support material. Static adsorption, solid‐phase extraction and high‐performance liquid chromatography were performed to investigate the adsorption properties and selective recognition characteristics of the polymer templates and their structural analogs. The maximum binding capacities of ofloxacin and 17β‐estradiol on the MTMIP were 9.0 and 6.6 mg/g, respectively. Compared with the corresponding nonimprinted polymer, the MTMIP exhibited a much higher adsorption performance and selectivity toward three quinolones and three estrogens, which are common drug residues in food. The MTMIP served as a simple and effective pretreatment method and could be successfully applied to the simultaneous analysis of multiple target components in complex samples. Furthermore, the MTMIP may find useful applications as a solid‐phase absorbent in the simultaneous determination of trace quinolones and estrogens in milk samples, as the recoveries were in the range 77.6–98.0%. Copyright © 2015 John Wiley & Sons, Ltd.     

Preparation of a stoichiometric molecularly imprinted polymer for auramine O and application in solid‐phase extraction

We describe a stoichiometric approach to the synthesis of molecularly imprinted polymers specific for auramine O. Using the stoichiometric interaction in molecular imprinting, no excess of binding sites is necessary and binding sites are only located inside the imprinted cavities. The free base of the template was obtained to facilitate the interaction with the monomers. Itaconic acid was selected as the functional monomer, and stoichiometric ratio of the interaction with the free base was investigated. The molecularly imprinted polymer preparation conditions such as cross‐linker, molar ratio, porogen were optimized as divinylbenzene, 1:2:20 and chloroform/N,N‐dimethylformamide, respectively. Under the optimum conditions, a good imprinting effect and very high selectivity were achieved. A solid‐phase extraction method was developed using the molecularly imprinted polymers as a sorbent and extraction procedure was optimized. The solid‐phase extraction method showed a high extraction recovery for auramine O in its hydrochloride form and free form compared to its analogues. The results strongly indicated that stoichiometric imprinting is an efficient method for development of high selectivity molecularly imprinted polymers for auramine O.     

Preconcentration of indapamide from human urine using molecularly imprinted solid‐phase extraction

A simple, sensitive, and selective molecularly imprinted solid‐phase extraction and spectrophotometric method has been developed for the clean‐up and preconcentration of indapamide from human urine. Molecularly imprinted polymers were prepared by a non‐covalent imprinting approach using indapamide as a template molecule, 2‐(trifluoromethyl) acrylic acid as a functional monomer, ethylene glycol dimethacrylate as a crosslinker, N,N‐azobisisobutyronitrile as a thermal initiator and acetonitrile as a porogenic solvent. A non‐imprinted polymer was also prepared in the same way, but in the absence of template. Molecularly imprinted polymer and non‐imprinted polymer sorbents were dry‐packed into solid‐phase extraction cartridges. Eluates from cartridges were analyzed using a spectrophotometer for the determination of indapamide by referring to the calibration curve in the range 0.14–1.50 μg/mL. Preconcentration factor, limit of detection, and limit of quantification were 16.30, 0.025 μg/mL, and 0.075 μg/mL, respectively. A relatively high imprinting factor (9.3) was also achieved and recovery values for the indapamide spiked into human urine were in the range of 80.1–81.2%. In addition, relatively low within‐day (0.17–0.42%) and between‐day (1.1–1.4%) precision values were obtained as well. The proposed molecularly imprinted solid‐phase extraction and spectrophotometric method was successfully applied to selective extraction, preconcentration, and determination of indapamide from human urine samples.     

Preparation of chitosan‐based molecularly imprinted material for enantioseparation of racemic mandelic acid in aqueous medium by solid phase extraction

An S‐mandelic acid imprinted chitosan resin was synthesized by cross‐linking chitosan with glutaraldehyde in 2% acetic acid solution. S‐Mandelic acid imprinted chitosan resin was used to enantioselectively separate racemic mandelic acid in aqueous medium. When keeping the pH of sample solution (100 mM Tris‐H₃PO₄) at 3.5 and adsorption time at 40 min, the enantiomer excess of mandelic acid in supernatant was 78.8%. The adsorption capacities of S‐mandelic acid imprinted chitosan resin for S‐ and R‐mandelic acid were determined to be 29.5 and 2.03 mg/g, respectively. While the adsorption capacities of non‐imprinted cross‐linked chitosan for S‐ and R‐mandelic acid were 2.10 and 2.08 mg/g, respectively. The result suggests that the imprinted caves in S‐mandelic acid imprinted chitosan resin are highly matched with S‐mandelic acid molecule in space structure and spatial arrangement of action sites. Interestingly, the enantiomer excess value of mandelic acid in supernatant after adsorption of racemic mandelic acid by R‐mandelic acid imprinted cross‐linked chitosan was 25.4%. The higher enantiomer excess value by S‐mandelic acid imprinted chitosan resin suggests that the chiral carbons in chitosan and the imprinted caves in S‐mandelic acid imprinted chitosan resin combine to play roles for the enantioselectivity of S‐mandelic acid imprinted chitosan resin toward S‐mandelic acid. Furthermore, the excellent enantioselectivity of S‐mandelic acid imprinted chitosan resin toward S‐mandelic acid demonstrates that using chiral chitosan as functional monomer to prepare molecularly imprinted polymers has great potential in enantioseparation of chiral pharmaceuticals.     

Synthesis of molecularly imprinted polypyrrole as an adsorbent for solid‐phase extraction of warfarin from human plasma and urine

The aim of this work was to develop a method for the clean‐up and preconcentration of warfarin from biological sample employing a new molecularly imprinted polymer (MIP) as a selective adsorbent for solid‐phase extraction (SPE). This MIP was synthesized using warfarin as a template, pyrrole as a functional monomer and vinyl triethoxysilane as a cross‐linker. The molar ratio of 1:4:20 (template–functional monomer–cross‐linker) showed the best results. Nonimprinted polymers (NIPs) were prepared and treated with the same method, but in the absence of warfarin. The prepared polymer was characterized by Fourier transmission infrared spectrometry and scanning electron microscopy. An adsorption process (SPE) for the removal of warfarin using the fabricated MIPs and NIPs was evaluated under various conditions. Effective parameters on warfarin extraction, for example, type and volume of elution solvent, pH of sample solution, breakthrough volume and maximum loading capacity, were studied. The limits of detection were in the range of 0.0035–0.0050 µg mL^?1. Linearity of the method was determined in the range of 0.0165–10.0000 µg mL^?1 for plasma and 0.0115–10.0000 µg mL^?1 for urine with coefficients of determination (R²) ranging from 0.9975 to 0.9985. The recoveries for plasma and urine samples were >95%. Copyright © 2015 John Wiley & Sons, Ltd.     

Design of selective molecularly imprinted sorbent for the optimized solid‐phase extraction of S‐pramipexole from the model multicomponent sample of human urine

The objective of this article was to design the selective molecularly imprinted sorbent dedicated to the solid‐phase extraction of S‐pramipexole from the complex matrix such as human urine. For that purpose, S‐2,6‐diamino‐4,5,6,7‐tetrahydrobenzothiazole was used as the template acting as the structural analog of S‐pramipexole and five various monomers were employed in the presence of ethylene glycol dimethacrylate to produce molecularly imprinted polymers. The binding capabilities of resulted polymers revealed that the highest imprinting effect was noted for polymer prepared from the itaconic acid. The comprehensive analysis of morphology and the characterization of binding sites showed not only negligible differences in the extension of surfaces of imprinted and nonimprinted polymers but also higher heterogeneity of binding sites in the imprinted material. Comprehensive optimization of the molecularly imprinted solid‐phase extraction allowed to select the most appropriate solvents for loading, washing, and elution steps. Subsequent optimization of mass of sorbent and volumes of solvents allowed to achieve satisfactory total recoveries of S‐pramipexole from the model multicomponent real sample of human urine that equals to 91.8 ± 3.2% for imprinted sorbent with comparison to only 37.1 ± 1.1% for Oasis MCX.     

Critical comparison of the on‐line and off‐line molecularly imprinted solid‐phase extraction of patulin coupled with liquid chromatography

Reaching trace amounts of mycotoxin contamination requires sensitive and selective analytical tools for their determination. Improving the selectivity of sample pretreatment steps covering new and modern extraction techniques is one way to achieve it. Molecularly imprinted polymers as selective sorbent for extraction undoubtedly meet these criteria. The presented work is focused on the hyphenation of on‐line molecularly imprinted solid‐phase extraction with a chromatography system using a column‐switching approach. Making a critical comparison with a simultaneously developed off‐line extraction procedure, evaluation of pros and cons of each method, and determining the reliability of both methods on a real sample analysis were carried out. Both high‐performance liquid chromatography methods, using off‐line extraction on molecularly imprinted polymer and an on‐line column‐switching approach, were validated, and the validation results were compared against each other. Although automation leads to significant time savings, fewer human errors, and required no handling of toxic solvents, it reached worse detection limits (15 versus 6 μg/L), worse recovery values (68.3–123.5 versus 81.2–109.9%), and worse efficiency throughout the entire clean‐up process in comparison with the off‐line extraction method. The difficulties encountered, the compromises made during the optimization of on‐line coupling and their critical evaluation are presented in detail.     

Preparation and application of molecularly imprinted polymer solid‐phase microextraction fiber for the selective analysis of auxins in tobacco

As signal molecules, auxins play an important role in mediating plant growth. Due to serious interfering substances in plants, it is difficult to accurately detect auxins with traditional solid‐phase extraction methods. To improve the selectivity of sample pretreatment, a novel molecularly imprinted polymer ‐coated solid‐phase microextraction fiber, which could be coupled directly to high‐performance liquid chromatography, was prepared with indole acetic acid as template molecule for the selective extraction of auxins. The factors influencing the polymer formation, such as polymerization solvent, cross‐linker, and polymerization time, were investigated in detail to enhance the performance of indole acetic acid‐molecularly imprinted polymer coating. The morphological and chemical stability of this molecularly imprinted polymer‐coated fiber was characterized by scanning electron microscopy, infrared spectrometry, and thermal analysis. The extraction capacity of the molecularly imprinted polymer‐coated solid‐phase microextraction fiber was evaluated for the selective extraction of indole acetic acid and indole‐3‐pyruvic acid followed by high‐performance liquid chromatography analysis. The linear range for indole acetic acid and indole‐3‐pyruvic acid was 1–100 µg/L and their detection limit was 0.5 µg/L. The method was applied to the simultaneous determination of two auxins in two kinds of tobacco (Nicotiana tabacum L and Nicotiana rustica L) samples, with recoveries range from 82.1 to 120.6%.     

Isolation and determination of estrogens in water samples by solid‐phase extraction using molecularly imprinted polymers and HPLC

Advanced SPE with molecularly imprinted polymers (MIP) was used in this study. A noncovalent imprinting approach was applied to separate 17β‐estradiol, estriol, and estrone from water samples. Polymer material was prepared by bulk polymerization with methacrylic acid as a functional monomer, divinylbenzene and ethyleneglycol dimethacrylate as crosslinkers, and acetonitrile, acetonitrile/toluene (3:1, v/v) or isooctane/toluene (1:99, v/v) as a porogen. We also prepared an MIP film on a silica gel surface with methacrylic acid and ethyleneglycol dimethacrylate as monomers and acetonitrile as a solvent. Qualitative and quantitative hormone analyses were carried out by HPLC with various detection techniques, including UV/visible spectroscopic detection (diode array detection) and electrochemical detection (CoulArray). The results of the study indicate that MIP technology is an excellent method for the quality control of estrogens in environmental analyses with a low quantification limit for 17β‐estradiol of around 26 (diode array detection) and 0.25 ng/mL (electrochemical detection). The proposed method was found to be suitable for routine determinations of the analyzed compound in environmental laboratories.     

Multifiber solid‐phase microextraction using different molecularly imprinted coatings for simultaneous selective extraction and sensitive determination of organophosphorus pesticides

Three types of molecularly imprinted solid‐phase microextraction fibers were fabricated through sol‐gel method using diazinon, parathion‐methyl, and isocarbophos as templates, respectively, and assembled together to construct a multifiber for analysis of organophosphorus pesticides in complex matrices. The multifiber provided large extraction capacity and high imprinting factor up to 3.89. In contrast, the imprinting factor of a single fiber was around 1.6, and the multi‐template imprinted coating showed no selectivity. The multifiber was applied to analyze pesticides in fruits and vegetables. The limits of detection, which ranged from 0.0052 to 0.23 µg/kg, were lower than those obtained by a single molecularly imprinted fiber, and much lower than those reported by other methods. The recoveries of five analytes in spiked apple, cucumber, Chinese cabbage, and cherry tomato samples were 75.1–123.2%. The study shows that the molecularly imprinted multifiber could achieve simultaneous selective extraction and sensitive determination of multiple targets in complex matrices for high‐throughput analysis.     

Determination of melamine in aquaculture feed samples based on molecularly imprinted solid‐phase extraction

This research highlights the application of highly efficient molecularly imprinted solid‐phase extraction for the preconcentration and analysis of melamine in aquaculture feed samples. Melamine‐imprinted polymers were synthesized employing methacrylic acid and ethylene glycol dimethacrylate as functional monomer and cross‐linker, respectively. The characteristics of obtained polymers were evaluated by scanning electron microscopy, Fourier transform infrared spectroscopy and binding experiments. The imprinted polymers showed an excellent adsorption ability for melamine and were applied as special solid‐phase extraction sorbents for the selective cleanup of melamine. An off‐line molecularly imprinted solid‐phase extraction procedure was developed for the separation and enrichment of melamine from aquaculture feed samples prior to high‐performance liquid chromatography analysis. Optimum molecularly imprinted solid‐phase extraction conditions led to recoveries of the target in spiked feed samples in the range 84.6–96.6% and the relative standard deviation less than 3.38% (n = 3). The aquaculture feed sample was determined, and there was no melamine found. The results showed that the molecularly imprinted solid‐phase extraction protocols permitted the sensitive, uncomplicated and inexpensive separation and pre‐treatment of melamine in aquaculture feed samples.     

Determination of macrolide antibiotics residues in pork using molecularly imprinted dispersive solid‐phase extraction coupled with LC–MS/MS

A class‐specific macrolide molecularly imprinted polymer was synthesized by precipitation polymerization using tulathromycin as the template and methacrylic acid as the functional monomer. The polymers revealed different specific adsorption and imprinting factor for macrolides with different spatial arrangement of side chains as well as lactonic ring size. And the molecularly imprinted polymer possessed maximum adsorption capacity (54.1 mg/g) and highest imprinting factor (2.4) toward 15‐membered ring azithromycin. On the basis of molecularly imprinted polymer dispersive solid‐phase extraction, a rapid, selective, and reproducible method for simultaneous determination of seven macrolide antibiotics residues in pork was established by using liquid chromatography with tandem mass spectrometry. At spiking levels of 5, 10, 25, and 100 μg/kg, average recoveries of seven macrolides ranged from 68.6 to 95.5% with intraday and interday relative standard deviations below 8%. The limits of detection and limits of quantification were 0.2–0.5 and 0.5–2.0 μg/kg, respectively.     

分子印迹聚合物固相萃取研究进展

对最新报道的分子印迹聚合物作为固相萃取剂及其在色谱样品前处理方面的应用进行综述和展望,主要包括固相萃取、基质固相分散萃取、固相微萃取、搅拌棒吸附萃取和磁性材料萃取,同时总结了分子印迹聚合物制备技术面临的挑战和问题,提出了可能的解决方案。     

Preparation of hydrophilic molecularly imprinted solid‐phase microextraction fiber for the selective removal and extraction of trace tetracyclines residues in animal derived foods

The present work reported a novel hydrophilic and selective solid‐phase microextraction fiber by improved multiple co‐polymerization method immobilization of tetracycline molecularly imprinted polymer on a stainless steel wire and directly coupled with high‐performance liquid chromatography for sensitive determination of trace tetracyclines residues in animal derived foods. The developed molecularly imprinted polymer coated solid‐phase microextraction fibers were characterized through scanning electron microscopy, Fourier transfer infrared spectroscopy, thermogravimetric analysis, and adsorption experiments, the fiber with cross‐linked and porous structure was observed and high thermal and chemical stability. The maximum adsorption capacity of this fiber with good selectivity reached 2.35 µg/mg in aqueous matrices, and showed good repeatability (relative standard deviation ≤ 6.6%, n = 5) and satisfying reproducibility between fiber to fiber (relative standard deviation ≤ 7.8%, n = 5). Under the optimized solid‐phase microextraction conditions, satisfactory linearity (5–1000 µg/L) and detection limits (0.38–0.72 µg/kg, S/N = 3) for all the tetracyclines were obtained. The practicality of this method was proved by adding tetracycline, oxytetracycline at three levels to milk, chicken, and fish samples with good recoveries of 77.3–104.4%.