Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 319
Filtrar
1.
Food Chem ; 339: 128079, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33152872

RESUMO

In this work, an efficient method for the determination of ß-agonists and fluoroquinolones was established, based on a mixed-mode sorbent of magnetic sulfonated covalent organic framework composites. By coupling with HPLC-MS/MS, the main factors that affect the extraction procedure were optimized. Under the optimal conditions, the proposed HPLC-MS/MS method was successfully utilized for the extraction of ß-agonists and fluoroquinolones in milk and pork meat samples. The method showed good linearities (R2 ≥ 0.9916), and low LOQs of 0.1-0.2 ng g-1 for ß-agonists and fluoroquinolones. The adsorption mechanism was investigated with the assistance of quantum chemistry calculation method, and it is worth noting that the sorbent relied mainly on the multiple adsorption mechanisms, including π-π stacking, hydrophobic, electrostatic attraction and hydrogen-bonding interactions. This work not only provides a simple method for the preparation of a mixed-mode sorbent, but also a routine analysis strategy for monitoring the illegal use of ß-agonists and fluoroquinolones.


Assuntos
Agonistas Adrenérgicos beta/análise , Fluoroquinolonas/análise , Análise de Alimentos/métodos , Imãs/química , Estruturas Metalorgânicas/síntese química , Extração em Fase Sólida/métodos , Ácidos Sulfônicos/química , Agonistas Adrenérgicos beta/química , Agonistas Adrenérgicos beta/isolamento & purificação , Adsorção , Animais , Técnicas de Química Sintética , Fluoroquinolonas/química , Fluoroquinolonas/isolamento & purificação , Contaminação de Alimentos/análise , Carne/análise , Estruturas Metalorgânicas/química , Leite/química , Suínos , Fatores de Tempo
2.
Food Chem ; 335: 127631, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32736157

RESUMO

In this work, sodium 4-styrenesulfonate functionalized polyacrylonitrile nanofibers mat (SS/PAN NFM) was firstly prepared and applied as 96-well plate solid-phase extraction adsorbent for quantitative determination of seven ß-agonists residues in pork samples. The functional modification endowed the SS/PAN NFM with superior adsorption performance for target ß-agonists. The adsorption process is spontaneous (ΔG < 0), the initial adsorption rate can reach 6.03-9.09 mg/g/min and the maximum adsorption capacity is calculated to be 48.3 mg/g at 298 K. Moreover, SS/PAN NFM can be reused for 12 times without degradation in adsorption capability. Combined with UPLC-MS/MS, the limits of detection can reach 0.006-0.24 µg/kg, the recoveries ranged from 87.2% to 111% and the relative standard deviations of intra-day and inter-day precisions were in the scope of 1.75%-11.6% and 5.08%-13.5%, respectively. The obtained results fully demonstrated the practicability of this method in preventing the hazard of ß-agonists residues.


Assuntos
Agonistas Adrenérgicos beta/análise , Agonistas Adrenérgicos beta/isolamento & purificação , Análise de Alimentos/métodos , Nanofibras/química , Poliestirenos/química , Carne Vermelha/análise , Extração em Fase Sólida/métodos , Resinas Acrílicas/química , Agonistas Adrenérgicos beta/química , Adsorção , Animais , Contaminação de Alimentos/análise , Limite de Detecção , Suínos
3.
AAPS PharmSciTech ; 21(4): 120, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32323091

RESUMO

The objective of this study was to develop a simpler and more practical quantitative evaluation method of cold flow (CF) in transdermal drug delivery systems (TDDSs). CF was forcibly induced by loading a weight on a punched-out sample (bisoprolol and tulobuterol tapes). When the extent of CF was analyzed using the area of oozed adhesive as following a previously reported method, the CF profiles were looked different between the samples 12 mm in diameter subjected to a 0.5-kg weight and samples 24 mm in diameter subjected to a 2.0-kg weight despite an equal load per unit area (4.42 g/mm2). The width of oozed adhesive around the original sample was suggested to be an index that properly describes the relationship between the load per unit area and the extent of CF. Further, it was clarified that the average CF width over the entire circumference of the sample was the same whether the samples were round or square as long as the sample area and load were the same. We also observed a linear relationship between the CF width and the aspect ratio of oval and rectangular samples. These results indicated that the CF properties of typical TDDS products lacking CF-proof processing at the edges could be determined by testing samples cut from the product rather than the whole TDDS patch. The proposed width measuring method was simple and useful for optimizing the composition of the adhesive and for testing the quality of the product.


Assuntos
Adesivos/farmacocinética , Temperatura Baixa , Sistemas de Liberação de Medicamentos/métodos , Terbutalina/análogos & derivados , Adesivos/administração & dosagem , Adesivos/química , Administração Cutânea , Agonistas Adrenérgicos beta/administração & dosagem , Agonistas Adrenérgicos beta/química , Agonistas Adrenérgicos beta/farmacocinética , Avaliação Pré-Clínica de Medicamentos/métodos , Terbutalina/administração & dosagem , Terbutalina/química , Terbutalina/farmacocinética
4.
Environ Toxicol Chem ; 38(11): 2509-2519, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31343770

RESUMO

The fish plasma model (FPM) predicts the fish blood plasma concentration of a pharmaceutical from the water concentration to which the fish is exposed and compares it with the human therapeutic plasma concentration (Hther PC) with the postulate that no adverse toxic effects occur below the Hther PC. The present study provides several lines of evidence supporting the FPM for the beta-adrenergic agonist salbutamol, a small cationic molecule at ambient pH. Salbutamol exhibited very low acute toxicity to early and adult life stages of fish. Biomass reduction in fish early life stages was the most sensitive apical endpoint, with no-observed-effect concentrations (NOECs) in the low mg/L range after continuous exposure for up to 120 d. Given that predicted and measured environmental concentrations are at least 1000-fold lower, the risk of salbutamol in freshwater is deemed very low. Increase in heart beat rate and decrease in total triglyceride content in fish also occurred at the low mg/L range and resembled effects known from humans. This finding supports the FPM assumption of conserved targets in fish with similar functionality. Plasma concentrations measured in adult and juvenile fish exposed to water concentrations at approximately the NOECs exceeded Hther PC and even approached plasma concentrations toxic to humans. This result confirms for salbutamol the FPM hypothesis that no adverse (i.e., population-relevant) toxic effects occur in fish below the Hther PC. Environ Toxicol Chem 2019;38:2509-2519. © 2019 SETAC.


Assuntos
Agonistas Adrenérgicos beta/sangue , Albuterol/sangue , Monitoramento Ambiental , Peixes/sangue , Modelos Biológicos , Agonistas Adrenérgicos beta/química , Albuterol/química , Animais , Biomassa , Frequência Cardíaca
5.
Mikrochim Acta ; 186(8): 552, 2019 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-31325046

RESUMO

Copper(II) polyphthalocyanine (CuPPc) was combined with graphitic carbon nitride (g-C3N4) to form a heterojunction with enhanced photoelectrochemical (PEC) signal. A sensitive PEC method was developed for determination of ractopamine based on a PEC inner filter effect between gold nanoparticles (AuNPs) and the g-C3N4/CuPPc. A gold electrode was modified with g-C3N4/CuPPc and the DNA was linked to the AuNPs. Initially, the PEC signal is weak due to the inner filter effect between the AuNPs and g-C3N4/CuPPc. In the presence of ractopamine, it interacts with the aptamer and the complementary chain (C chain) is released. This triggers the entropy-driven cyclic amplification and results in the release of the substrate B chain (SB chain) from three-dimensional DNA stabilizer. The probe is released from the electrode due to the interaction of probe DNA and the SB chain. As a result, the PEC signal increases linearly in the 0.1 pmol·L-1 to 1000 pmol·L-1 ractopamine concentration range. The detection limit is 0.03 pM, and the relative standard deviation is 3.4% (at a 10 pmol·L-1 level; for n = 11). The method has been successfully applied to the determination of ractopamine in pork samples. Graphical abstract Schematic presentation of detection method based on PEC inner filter effect between AuNPs and the g-C3N4/CuPPc being fabricated for ractopamine. 3D DNA was used as stabilizer to decrease the PEC blank signal.


Assuntos
Agonistas Adrenérgicos beta/análise , Grafite/química , Indóis/química , Nanopartículas Metálicas/química , Compostos de Nitrogênio/química , Compostos Organometálicos/química , Fenetilaminas/análise , Agonistas Adrenérgicos beta/química , Aptâmeros de Nucleotídeos/química , DNA/química , Técnicas Eletroquímicas , Contaminação de Alimentos/análise , Ouro , Luz , Fenetilaminas/química , Processos Fotoquímicos , Carne de Porco/análise
6.
Mikrochim Acta ; 186(8): 515, 2019 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-31280384

RESUMO

A visualization strategy is described for the detection of clenbuterol (CLB). It is using of antibody against dsDNA and G-quadruplex/hemin labeled on a metal organic framework of type MIL-101(Fe) (G-quadruplex/hemin-anti-DNA/MIL-101) acting as a peroxidase mimetic, and magnetic beads modified with aptamer and complementary DNA (MB/Apt-cDNA) as capture probes. The detection reagent was prepared via the reactions between the double stranded DNA (Apt-cDNA) in capture probes and anti-DNA in peroxidase mimetic. In the presence of CLB, the aptamer on the magnetic beads preferentially binds CLB, and the peroxidase mimetic is released to the supernatant after magnetic separation. The released peroxidase mimetic can catalyze the TMB/H2O2 chromogenic system under mild conditions. This leads to the development of a blue-green coloration whose absorbance is measured at 650 nm. The detection limit is as low as 34 fM of CLB. The method was applied to the determination of CLB in pork samples and gave results that were consistent with data obtained with an ELISA kit. Graphical abstract A visualization strategy is described for the detection of clenbuterol. The selectivity of detection system for clenbuterol is excellent compared with other interferents. The method was applied to the determination of CLB in pork samples.


Assuntos
Agonistas Adrenérgicos beta/análise , Clembuterol/análise , Contaminação de Alimentos/análise , Carne Vermelha/análise , Suínos , Agonistas Adrenérgicos beta/química , Animais , Anticorpos/química , Aptâmeros de Nucleotídeos/química , Biomimética , Clembuterol/química , Colorimetria , DNA/química , DNA/imunologia , Quadruplex G , Hemina/química , Ferro/química , Fenômenos Magnéticos , Estruturas Metalorgânicas/química , Peroxidase/química
7.
Electrophoresis ; 40(21): 2828-2836, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31238386

RESUMO

In this study, a simple and effective method was developed for the enantiomeric analysis of five ß-agonists (terbutaline, clorprenaline, tulobuterol, clenbuterol, and salbutamol) in water samples using deep eutectic solvent (DES) based dispersive liquid-liquid microextraction and chiral LC-MS. In such a framework, different kinds of hydrophobic DESs were tailored to examine their extraction ability for five ß-agonists from aqueous sample. After an initial screening, the primary factors affecting the extraction recovery of DES based dispersive liquid-liquid microextraction, such as hydrogen-bond acceptor/hydrogen-bond donor ratio, DES volume, type and volume of disperser solvent and so on, were investigated and optimized. Finally, the established method was validated and found to be linear, precise, and accurate. The method was successfully applied to analyze the five ß-agonists in water samples, which will help better understand the behavior of individual enantiomer and make accurate risk assessment on the ecosystem.


Assuntos
Agonistas Adrenérgicos beta/análise , Cromatografia Líquida de Alta Pressão/métodos , Microextração em Fase Líquida/métodos , Espectrometria de Massas/métodos , Poluentes Químicos da Água/análise , Agonistas Adrenérgicos beta/química , Agonistas Adrenérgicos beta/isolamento & purificação , Interações Hidrofóbicas e Hidrofílicas , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Solventes/química , Estereoisomerismo , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação
8.
J Labelled Comp Radiopharm ; 62(11): 707-712, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31215663

RESUMO

A medicinal chemistry program to develop potent and selective LABA compounds required the synthesis of both carbon-14 and stable-isotope labelled materials.  Carbon-14 labelled AZD7307 was successfully synthesised in 6 steps from [14C]chloroacetyl chloride in an overall radiochemical yield of 10%. In addition, the synthetic route of a stable labelled isotopomer of AZD7307 is also described and synthesised in four linear steps from [13C6]cyclohexylamine hydrochloride in an overall yield of 12%.


Assuntos
Agonistas Adrenérgicos beta/química , Agonistas Adrenérgicos beta/síntese química , Radioisótopos de Carbono/química , Receptores Adrenérgicos beta 2/metabolismo , Técnicas de Química Sintética , Marcação por Isótopo , Radioquímica
9.
J Med Chem ; 62(10): 5111-5131, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31042379

RESUMO

Starting from the ß-adrenoceptor agonist isoprenaline and beta-blocker carvedilol, we designed and synthesized three different chemotypes of agonist/antagonist hybrids. Investigations of ligand-mediated receptor activation using bioluminescence resonance energy transfer biosensors revealed a predominant effect of the aromatic head group on the intrinsic activity of our ligands, as ligands with a carvedilol head group were devoid of agonistic activity. Ligands composed of a catechol head group and an antagonist-like oxypropylene spacer possess significant intrinsic activity for the activation of Gαs, while they only show weak or even no ß-arrestin-2 recruitment at both ß1- and ß2-AR. Molecular dynamics simulations suggest that the difference in G protein efficacy and ß-arrestin recruitment of the hybrid ( S)-22, the full agonist epinephrine, and the ß2-selective, G protein-biased partial agonist salmeterol depends on specific hydrogen bonding between Ser5.46 and Asn6.55, and the aromatic head group of the ligands.


Assuntos
Agonistas Adrenérgicos beta/química , Antagonistas Adrenérgicos beta/química , Proteínas de Ligação ao GTP/efeitos dos fármacos , Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Carvedilol/síntese química , Carvedilol/química , Catecóis/química , Desenho de Fármacos , Humanos , Ligação de Hidrogênio , Indicadores e Reagentes , Isoproterenol/síntese química , Isoproterenol/química , Ligantes , Camundongos , Modelos Moleculares , Simulação de Dinâmica Molecular , Xinafoato de Salmeterol/farmacologia , beta-Arrestinas/efeitos dos fármacos , beta-Arrestinas/metabolismo
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 219: 444-449, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31063959

RESUMO

Isoxsuprine (ISX) is widely used for cerebral and peripheral vascular diseases. A comparative study was held among different multivariate calibration models for selective determination of a complex mixture of Isoxsuprine and four of its toxic photothermal degradation products that impair kidney and liver functions. The Partial Least Squares (PLS) and Artificial Neural Network (ANN) models were applied on the specific spectrum and on selected wavelengths using genetic algorithm (GA) technique as an efficient variable selection tool. The effect of GA on the model construction and performance was evaluated. The multilevel multifactor experimental design was adopted for the construction of the calibration set. Optimized parameters were used for the development of the different models. The performances of the developed models were assessed by predicting the concentration of eight different mixtures composing the validation set. Results were compared to one another and to the official method using one-way ANOVA statistical test to assure the validity of the constructed models. The lower chance of overfitting offered by ANN minimized the RMSEP relative to the PLS. On the other hand, the application of GA prior to model implementation affected the number of latent variables the prediction ability of both PLS and ANN models. The validated models were successfully applied as stability indicating assay methods for the selective determination of ISX and its photothermal degradation products in ISX raw material and market formulations.


Assuntos
Agonistas Adrenérgicos beta/química , Isoxsuprina/química , Algoritmos , Estabilidade de Medicamentos , Análise dos Mínimos Quadrados , Redes Neurais de Computação , Fotólise , Espectrofotometria Ultravioleta , Temperatura
11.
Artigo em Inglês | MEDLINE | ID: mdl-29571118

RESUMO

An analytical procedure for the analysis of 10 ß-adrenergic agonists (cimaterol, terbutaline, salbutamol, isoxsuprine, ractopamine, cimbuterol, clenbuterol, brombuterol, mabuterol and mapenterol) in pork meat was developed and validated using LC-MS/MS. An automated dispersive pipette extraction (DPX) was employed on a Hamilton Microlab® NIMBUS96® platform to extract the analytes of interest prior to LC-MS/MS analysis. The extraction time was <20 min with a total LC-MS/MS run time of 9.6 min. The method was fully validated in accordance with the international guidelines (European Commission Decision 2002/657/EC and National Standards of People's Republic of China, GB/T 22286-2008) for limit of detection, limit of quantitation, carryover, extraction efficiency, matrix effects, linearity, and within and between-run precision. The proposed method can be successfully used in the routine determination of 10 ß-adrenergic agonists in pork and as a potential solution for compliance monitoring in regulatory laboratories.


Assuntos
Agonistas Adrenérgicos beta/análise , Automação/métodos , Cromatografia Líquida/métodos , Resíduos de Drogas/análise , Carne/análise , Espectrometria de Massas em Tandem/métodos , Agonistas Adrenérgicos beta/química , Agonistas Adrenérgicos beta/isolamento & purificação , Animais , Fracionamento Químico , Resíduos de Drogas/química , Resíduos de Drogas/isolamento & purificação , Modelos Lineares , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Suínos
12.
Sci Rep ; 7(1): 12319, 2017 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-28951558

RESUMO

Visualization of the G-protein coupled receptor (GPCR) is of great importance for studying its function in a native cell. We have synthesized a series of red-emitting fluorescent probes targeting ß-adrenergic receptor (ßAR) that are compatible with confocal and Stimulated Emission Depletion (STED) microscopy as well as with Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) binding assay in living cells. The probe based on the agonist BI-167107 and fluorescent dye KK114 demonstrates nanomolar binding affinity and up to nine-fold ß2AR selectivity over ß1AR. Carazolol-derived probes are fluorogenic and allow no-wash imaging experiments. STED microscopy of ß2ARs stained at the native expression level on pancreatic CAPAN cells provides two-fold improvement in lateral optical resolution over confocal mode and reveals the formation of receptor microdomains. These probes retain their functional (agonist or antagonist) properties, allowing simultaneous modulation of cyclic adenosine monophosphate (cAMP) levels and receptor internalization as well as imaging receptor localization.


Assuntos
Agonistas Adrenérgicos beta/química , Imagem Molecular/métodos , Sondas Moleculares/química , Receptores Adrenérgicos beta 1/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Linhagem Celular Tumoral , Transferência Ressonante de Energia de Fluorescência/métodos , Corantes Fluorescentes/química , Células HEK293 , Humanos , Microscopia Intravital/métodos , Ligantes , Microscopia Confocal/métodos , Sondas Moleculares/farmacologia
13.
Curr Med Chem ; 24(39): 4340-4359, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28738772

RESUMO

BACKGROUND: Evolution in computer engineering, availability of increasing amounts of data and the development of new and fast docking algorithms and software have led to improved molecular simulations with crucial applications in virtual high-throughput screening and drug discovery. Moreover, analysis of protein-ligand recognition through molecular docking has become a valuable tool in drug design. OBJECTIVE: In this review, we focus on the applicability of molecular docking on a particular class of G protein-coupled receptors: the ß-adrenergic receptors, which are relevant targets in clinic for the treatment of asthma and cardiovascular diseases. RESULTS: We describe the binding site in ß-adrenergic receptors to understand key factors in ligand recognition along with the proteins activation process. Moreover, we focus on the discovery of new lead compounds that bind the receptors, on the evaluation of virtual screening using the active/ inactive binding site states, and on the structural optimization of known families of binders to improve ß-adrenergic affinity. We also discussed strengths and challenges related to the applicability of molecular docking in ß-adrenergic receptors. CONCLUSION: Molecular docking is a valuable technique in computational chemistry to deeply analyze ligand recognition and has led to important breakthroughs in drug discovery and design in the field of ß-adrenergic receptors.


Assuntos
Asma/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Descoberta de Drogas , Simulação de Acoplamento Molecular , Receptores Adrenérgicos beta/metabolismo , Agonistas Adrenérgicos beta/química , Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/química , Antagonistas Adrenérgicos beta/farmacologia , Algoritmos , Asma/metabolismo , Doenças Cardiovasculares/metabolismo , Ensaios de Triagem em Larga Escala , Humanos , Software
14.
Artigo em Inglês | MEDLINE | ID: mdl-28431781

RESUMO

Clenbuterol (Broncodil and trade) is a direct-acting sympathomimetic agent with mainly beta-adrenergic activity and a selective action on ß2 receptors (a ß2 agonist). It has properties similar to those of salbutamol. It is used as a bronchodilator in the management of reversible airways obstruction, as in asthma and in certain patients with chronic obstructive pulmonary disease. The uses, applications, and the synthetic pathways of this drug are outlined. Physical characteristics including: ionization constant, solubility, X-ray powder diffraction pattern, thermal methods of analysis, UV spectrum, IR spectrum, mass spectrum are all produced. This profile also includes the monograph of British Pharmacopoeia, together with several reported analytical methods including spectrophotometric, electrochemical, chromatographic, immunochemical methods, and capillary electrophoretic methods. The stability, the pharmacokinetic behavior, and the pharmacology of the drug are also provided.


Assuntos
Clembuterol , Agonistas Adrenérgicos beta/química , Agonistas Adrenérgicos beta/farmacocinética , Agonistas Adrenérgicos beta/farmacologia , Agonistas Adrenérgicos beta/uso terapêutico , Animais , Asma/tratamento farmacológico , Broncodilatadores/química , Broncodilatadores/farmacocinética , Broncodilatadores/farmacologia , Broncodilatadores/uso terapêutico , Clembuterol/química , Clembuterol/farmacocinética , Clembuterol/farmacologia , Clembuterol/uso terapêutico , Humanos , Estrutura Molecular , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Simpatomiméticos/química , Simpatomiméticos/farmacocinética , Simpatomiméticos/farmacologia , Simpatomiméticos/uso terapêutico
15.
J Agric Food Chem ; 65(19): 3965-3974, 2017 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-28453289

RESUMO

4-[2-(t-Butylamino)-1-hydroxyethyl]phenol (buctopamine, 4), a new ß2 receptor agonist (ß2-agonist), was found to be an adulterant in feed additives for swine in Taiwan, where using ß2-agonists in food-production animals is prohibited. Buctopamine and its metabolite, 4-[2-(t-butylamino)-1-hydroxyethyl]-2-methoxyphenol (mebuctopamine, 2), were detected in swine hair specimens. Authentic compounds 2 and 4 were synthesized with 98.6% and 97.7% purity, respectively, as reference standards for analysis, and both compounds were more hydrophilic than ractopamine and clenbuterol. In a preliminary pharmacological evaluation, compounds 2 and 4 exhibited moderate human ß2 receptor binding affinity and did not show significant affinities for the human α1, α2, ß1, and ß3 receptors. After addition of compounds 2-4 into the ß2-agonist library, a multiresidue analysis of 26 ß2-agonists by using triple quadrupole LC/MS/MS for routine screening conducted by regulatory authorities was established, in which the common limits of quantification for the 26 ß2-agonists in swine feed and hair are 10 and 25 ng/g, respectively. In addition, the illegal use of buctopamine (4) has been effectively prevented. The results of this study are also useful for controlling the illegal use of new ß2-agonists in food-production animals.


Assuntos
Agonistas Adrenérgicos beta/química , Agonistas Adrenérgicos beta/metabolismo , Ração Animal/análise , Cabelo/química , Animais , Aditivos Alimentares/química , Aditivos Alimentares/metabolismo , Cabelo/metabolismo , Estrutura Molecular , Suínos , Taiwan
16.
Food Chem ; 228: 62-69, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28317772

RESUMO

As an ideal biomimetic antibody, molecularly imprinted polymer (MIP) has shown great promise in immunoassays. Here, we developed a covalent imprinting method to prepare MIP artificial antibody towards clenbuterol on the well surface of a microtiter plate. Template molecule (clenbuterol) was splited by hydrolysis with functional monomer and removed by methanol/acetic acid solution, and then three-dimensional cavities were fabricated in the MIP, which can rebind template molecule via hydrogen bond interaction. Using this artificial antibody, we developed a novel biomimetic enzyme-linked immunosorbent assay (ELISA) with excellent sensitivity and specificity. The linear range for clenbuterol was 10-5 to 1000µgL-1, with a detection limit of 10-7µgL-1. Cross reactivity of this MIP artificial antibody to other four structural analogs was less than 0.93%. This method was applied to determine clenbuterol in real samples with satisfactory result, suggesting a promising application of the biomimetic ELISA in food and environmental analysis.


Assuntos
Agonistas Adrenérgicos beta/química , Biomimética/métodos , Clembuterol/análise , Clembuterol/química , Impressão Molecular/métodos , Polímeros/química , Agonistas Adrenérgicos beta/análise , Anticorpos
17.
Food Chem ; 227: 315-321, 2017 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-28274437

RESUMO

A selective analytical method based on packed-fiber solid-phase extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (PFSPE-UPLC-MS/MS) has been developed for determination of six ß-agonists (clorprenaline, bambuterol, clenbuterol, brombuterol, mabuterol, and penbuterol) in pork tissue. Polystyrene-polymeric crown ether (PS-PCE) composite nanofibers were fabricated by electrospinning and utilized to prepare the homemade extraction columns. With optimal conditions, all analytes were separated very well and the blank pork did not disturb the determination, and the linearity is good in a range of 5.0µg/kg-25.0µg/kg. The recoveries were 79.3-110.1%. RSDs for intra-day were in the range of 1.5-10.5% and RSDs for inter-day were 4.7-11.8%. Above all, only 5mg of sorbent and 200µL of elution solvent were favorable to directly extract all analytes in a complex matrix. The method is simple and cost-effective, and has the potential to be applied to quantitatively analyze the concentrations of polar species in food samples containing complex matrix.


Assuntos
Agonistas Adrenérgicos beta/química , Agonistas Adrenérgicos beta/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Carne/análise , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Drogas Veterinárias/isolamento & purificação , Compostos de Anilina/análise , Compostos de Anilina/isolamento & purificação , Animais , Clembuterol/análogos & derivados , Clembuterol/análise , Clembuterol/isolamento & purificação , Resíduos de Drogas/química , Resíduos de Drogas/isolamento & purificação , Etanolaminas/análise , Etanolaminas/isolamento & purificação , Contaminação de Alimentos/análise , Limite de Detecção , Nanofibras/análise , Polímeros/análise , Poliestirenos/química , Extração em Fase Sólida/instrumentação , Suínos , Drogas Veterinárias/química
18.
J Chromatogr A ; 1486: 59-67, 2017 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-28049585

RESUMO

Quantitative structure-retention relationship (QSRR) models are developed to predict the retention times of analytes on five hydrophilic interaction liquid chromatography (HILIC) stationary phases (bare silica, amine, amide, diol and zwitterionic), with a view to selecting the most suitable stationary phase(s) for the separation of these analytes. The study was conducted using six ß-adrenergic agonists as target analytes. Molecular descriptors were calculated based only on chemical structures optimized using density functional theory. A genetic algorithm (GA) was then used to select the most relevant molecular descriptors and these were used to build a retention model for each stationary phase using partial least squares (PLS) regression. This model was then used to predict the retention of the test set of target analytes. This process created an optimized descriptor set which enhanced the reliability of the developed QSRR models. Finally, the QSRR models developed in the work were utilized to provide some insight into the separation mechanisms operating in the HILIC mode. Three performance criteria - mean absolute error (MAE), root mean square error of prediction scaled to retention time (RMSEP), and the number of selected descriptors, were used to evaluate the developed models when applied to an external test set of six ß-adrenergic agonists and showed highly predictive abilities. MAE values ranged from 13 to 25s on four of the stationary phases, with a somewhat higher error (50s) being observed for the zwitterionic phase. RMSEP values of 4.88-11.12% were recorded. Validation was performed through Y-randomization and chemical domain applicability, from which it was evident that the developed optimized GA-PLS models were robust. The high levels of accuracy, reliability and applicability of the models were to a large extent due to the optimization of the GA descriptor set and the presence of relevant structural and geometric molecular descriptors, together with descriptors based on important physicochemical properties, which establish a strong connection between retention time and meaningful chemical properties. The present strategy, while it is a pilot study, holds great promise for broader screening of HILIC stationary phases for desired separation, as well as for acquisition of information about molecular mechanisms of separation under chromatographic conditions.


Assuntos
Agonistas Adrenérgicos beta/química , Agonistas Adrenérgicos beta/isolamento & purificação , Cromatografia Líquida/métodos , Interações Hidrofóbicas e Hidrofílicas , Modelos Químicos , Algoritmos , Amidas/química , Aminas/química , Análise dos Mínimos Quadrados , Projetos Piloto , Relação Quantitativa Estrutura-Atividade , Teoria Quântica , Reprodutibilidade dos Testes , Dióxido de Silício/química , Soluções
19.
Chem Biol Drug Des ; 90(1): 119-127, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28054456

RESUMO

The rat fat cell ß-adrenoceptors were investigated by studying the effects of new 1,8-naphthyridine derivatives synthesized starting from 7-amino-2-chloro-3-phenyl-1,8-naphthyridine on lipolysis induced by isoprenaline, and alprenolol. Lipolysis induced by isoprenaline agonist was competitively antagonized by the 1,8-naphthyridine analogue with a 7-hydroxy-2-(4'-methoxybenzylamine)-6-nitro-3-phenyl substituent designated as 3. In contrast, 10, 50, and 100 µm of 7-methoxy and 7-ethoxy derivatives did not modify the concentration-response curve of isoprenaline. A rightward shift of the curve was, however, observed with 50 µm of a 7-methoxy-2-(4'-methoxybenzylamine)-6-amino-3-phenyl substituent designated as 10. The selective ß1 -AR antagonist, 7-hydroxy-4-morpholinomethyl-2-piperazino-1,8-naphthyridine slightly reduced isoprenaline-induced lipolysis only at high doses. Alprenolol-mediated lipolytic effect was antagonized by derivative 3, 10 and the selective ß3 -AR antagonist SR 59,230A, but resistant to the selective ß1 -AR antagonist 7-hydroxy-4-morpholinomethyl-2-piperazino-1,8-naphthyridine. The results provide preliminary pharmacological evidence for the antilipolytic effect of the newly synthesized 1,8-naphthyridine derivatives on rat fat cells. The analogues designated as 3 and 10 were the most potent antagonists of this series.


Assuntos
Antagonistas Adrenérgicos beta/química , Naftiridinas/química , Receptores Adrenérgicos beta/metabolismo , Adipócitos Brancos/citologia , Adipócitos Brancos/efeitos dos fármacos , Adipócitos Brancos/metabolismo , Agonistas Adrenérgicos beta/síntese química , Agonistas Adrenérgicos beta/química , Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/síntese química , Antagonistas Adrenérgicos beta/farmacologia , Alprenolol/farmacologia , Animais , Etanolaminas/farmacologia , Isoproterenol/farmacologia , Lipólise/efeitos dos fármacos , Naftiridinas/síntese química , Naftiridinas/farmacologia , Ratos , Receptores Adrenérgicos beta/química , Tetra-Hidronaftalenos/farmacologia
20.
J Sci Food Agric ; 97(3): 1001-1009, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27247162

RESUMO

BACKGROUND: All ß-agonists are banned as feed additives for growth promotion in animals due to toxic effects on humans after consuming the ß-agonist contaminated meats. Phenylethanolamine A (PA) is a newly emerged ß-agonist. Thus there is a need to develop highly sensitive and specific analytical methods for the detection of PA in food samples. In this study, the monoclonal antibody (mAb) against PA was produced by hybridoma technology and used for the development of enzyme-linked immunosorbent assay (ELISA). RESULTS: The IC50 values and limits of detection (LODs) of the ELISA using homogeneous combination of coating antigen/antibody for PA were 0.16 ng mL-1 and 0.011 ng mL-1 , respectively. The cross-reactive (CR) values of the assay with 14 structurally related ß-agonists were lower than 0.59%. Swine liver and meat samples were spiked with PA at different content and analysed by ELISA. Acceptable recovery rates of 91.40-105.51% and intra-assay coefficients of variation of 1.56-9.92% (n = 3) were obtained. The ELISA for seven spiked samples was confirmed by LC-MS/MS with a high correlation coefficient of 0.9881. CONCLUSION: The proposed mAb-based ELISA was highly sensitive and specific for PA and could be used as a quantitative/screening method for PA analysis in food samples. © 2016 Society of Chemical Industry.


Assuntos
2-Hidroxifenetilamina/análogos & derivados , Agonistas Adrenérgicos beta/análise , Anticorpos Monoclonais/metabolismo , Especificidade de Anticorpos , Resíduos de Drogas/análise , Ensaio de Imunoadsorção Enzimática , Inspeção de Alimentos/métodos , 2-Hidroxifenetilamina/análise , 2-Hidroxifenetilamina/química , 2-Hidroxifenetilamina/metabolismo , Agonistas Adrenérgicos beta/química , Agonistas Adrenérgicos beta/metabolismo , Animais , China , Cromatografia Líquida de Alta Pressão , Reações Cruzadas , Resíduos de Drogas/química , Resíduos de Drogas/metabolismo , Contaminação de Alimentos , Haptenos/química , Haptenos/metabolismo , Limite de Detecção , Fígado/química , Carne/análise , Estrutura Molecular , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray , Sus scrofa , Espectrometria de Massas em Tandem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA