RESUMO
A novel and robust electrochemical sensing tool for the determination of vismodegib (VIS), an anticancer drug, has been developed by integrating the selective recognition capabilities of molecularly imprinted polymer (MIP) and the sensitivity enhancement capability of metal-organic framework (MOF). Prior to this step, the electrochemical behavior of VIS was investigated using a bare glassy carbon electrode (GCE). It was observed that in 0.5 M H2SO4 solution as electrolyte, VIS has an oxidation peak around 1.3 V and the oxidation mechanism is diffusion controlled. The determination of VIS in a standard solution using a bare GCE showed a linear response in the concentration range from 2.5 µM to 100 µM, with a limit of detection (LOD) of 0.75 µM. Since sufficient sensitivity and selectivity could not be achieved with bare GCE, a MIP sensor was developed in the next step of the study. For this purpose, the GCE surface was first modified by drop casting with as-synthesized Co-MOF. Subsequently, a MIP network was synthesized via a thermal polymerization approach using 2-acrylamido-2-methylpropanesulfonic acid (AMPS) as monomer and VIS as template. MOFs are ideal electrode materials due to their controllable and diverse morphologies and modifiable surface properties. These characteristics enable the development of MIPs with more homogeneous binding sites and high affinity for target molecules. Integrating MOFs could help the performance of sensors with the desired stability and reproducibility. Electrochemical analysis revealed an observable enhancement of the output signal by the incorporation of MOF molecules, which is consistent with the sensitivity-enhancing role of MOF by providing more anchoring sites for the attachment of the polymer texture to the electrode surface. This MOF-MIP sensor exhibited impressive linear dynamic ranges ranging from 0.1 to 1.0 pM for VIS, with detection limits in the low picomolar range. In addition, the MOF-MIP sensor offers high accuracy, selectivity and precision for the determination of VIS, with no interference observed from complex media of serum samples. Additionally, in this study, Analytical GREEnness metric (AGREE), Analytical GREEnness preparation (AGREEprep) and Blue Applicability Grade Index (BAGI) were used to calculate the green profile score.
Assuntos
Anilidas , Antineoplásicos , Técnicas Eletroquímicas , Eletrodos , Estruturas Metalorgânicas , Polímeros Molecularmente Impressos , Piridinas , Estruturas Metalorgânicas/química , Polímeros Molecularmente Impressos/química , Piridinas/química , Técnicas Eletroquímicas/métodos , Antineoplásicos/análise , Antineoplásicos/química , Antineoplásicos/sangue , Anilidas/química , Anilidas/análise , Anilidas/sangue , Limite de Detecção , Impressão Molecular , Polímeros/químicaRESUMO
Ostarine, also known as S22 or MK2866 and enobosarm, is a selective androgen receptor modulator (SARM). It has high anabolic potency, in addition to limited androgenic effects. At this time, ostarine has no therapeutic use, but can be abused for performance-enhancing purposes using the oral route, at dosages of 10-25 mg per day. As the drug can easily be obtained via the Internet or some fitness centers, athletes and more and more amateurs can use it without undergoing the deleterious physiological side effects that are generally associated with testosterone-related compounds. Since 2008, the World Anti-Doping Agency (WADA) has prohibited SARMs at-all-times in the category of "other anabolic agents" under section S1.2 of the WADA List. In a case of trafficking/abuse, ostarine was identified in nail (subject 1) and hair (subject 2) by LC/HRMS after incubation of 50 mg of matrix in a pH 9.5 buffer, followed by extraction with organic solvents. The drug was quantitated by LC-MS/MS. Ostarine tested positive at 61 pg/mg (toenails) and 111 pg/mg (fingernails) for subject 1. Ostarine was present at 146, 168, 93, and 101 pg/mg in the 4 × 3 cm hair sections of subject 2, clearly demonstrating long-term use.
Assuntos
Anilidas/análise , Cromatografia Líquida/métodos , Cabelo/química , Unhas/química , Anabolizantes/análise , Dopagem Esportivo/prevenção & controle , Humanos , Espectrometria de Massas/métodos , Detecção do Abuso de Substâncias/métodos , Espectrometria de Massas em Tandem/métodosRESUMO
This study involves spectroscopic analysis of pesticide residues extracted from tomato, one of the most freshly eaten fruit all over the world. In Egypt, tomato can be protected against pests infection by concomitantly spraying three pesticides namely, acetamiprid (AC), flutolanil (FL) and etofenprox (ET). The three pesticides have been simply and efficiently extracted from the fruits and analyzed by applying the following methods: Differential dual wavelength method, where AC, FL and ET were determined by amplitudes subtraction at 264.8-277 nm, 229-241 nm and 225.6 and 243 nm, respectively after obtaining their first derivative spectra. Modified ratio difference method, where the difference in amplitude values at 261.2 and 241 nm, 273.4 and 236.8 nm and 269.8 and 232 nm was used for determination of AC, FL and ET, respectively. The third method includes recording the amplitudes at 284, 293 and 224 nm for AC, FL and ET, respectively, after mean centering of their spectra. The linear ranges were 1-11, 0.2-2.5 and 0.2-2.5 µg mL-1 for AC, FL and ET, respectively. The methods were proven to be green regarding the Eco-Scale calculations. The methods were efficiently applied for determination of AC, FL and ET in their commercial forms and field trials, where the residues were approximately equal to or below their specified maximum residue limits.
Assuntos
Anilidas/análise , Neonicotinoides/análise , Resíduos de Praguicidas/análise , Piretrinas/análise , Solanum lycopersicum/química , Frutas/química , Espectrofotometria Ultravioleta/métodosRESUMO
An increase in the area treated with the fungicide thifluzamide has triggered concerns for soil ecosystem service providers such as earthworms. Here, we assessed effects of thifluzamide on earthworm (Eisenia fetida) biomarker indicators of stress responses and reproduction following exposure to 0, 0.1, 1.0, and 10.0â¯mg of thifluzamide kg-1 soil for 7, 14, 21, and 28â¯d (biomarker indicators) and 30â¯d (reproduction). Growth and reproduction were inhibited by exposure to thifluzamide at 10.0â¯mg/kg, and the activities of succinate dehydrogenase (SDH) and respiratory chain complex II were inhibited by exposure to 1.0 and 10.0â¯mg/kg thifluzamide for the majority of the 28-d experiment. Reactive oxygen species (ROS) increased across all thifluzamide treatments, and the activities of superoxide dismutase (SOD) and glutathione-S-transferase (GST) tended to be inhibited by thifluzamide. Upon exposure to thifluzamide, the activities of catalase (CAT) and guaiacol peroxidase (POD) initially increased and then decreased. Increased levels of malondialdehyde (MDA) were detected only at seven days after exposure, and genotoxicity increased as the thifluzamide concentration increased. The results suggest that thifluzamide presents a potential risk to earthworms at the concentration of 10.0â¯mg/kg, and its use should be moderated to reduce damage to soil ecosystem function.
Assuntos
Anilidas/toxicidade , Oligoquetos/efeitos dos fármacos , Praguicidas/toxicidade , Poluentes do Solo/toxicidade , Tiazóis/toxicidade , Anilidas/análise , Animais , Antioxidantes/metabolismo , Dano ao DNA , Biomarcadores Ambientais/efeitos dos fármacos , Oligoquetos/crescimento & desenvolvimento , Oligoquetos/metabolismo , Oligoquetos/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Praguicidas/análise , Reprodução/efeitos dos fármacos , Poluentes do Solo/análise , Tiazóis/análiseRESUMO
Herein, contaminants remaining in distillate and distillers' stillage were quantitatively measured after distillation. After rice bran powder was contaminated with 10 ppm of lead (Pb) and cadmium (Cd) or 0.02-1.27 ppm of five pesticides (terbufos, fenthion, iprobenfos, flutolanil, and ethoprophos) followed by fermentation, single-stage distillation was performed. In the obtained distillate, no Pb or Cd was found, as expected. However, when the pesticides were added as contaminants, trace-0.05 ppm of some pesticides were detected in the distillate, possibly due to the high vapor pressure (e.g., that of ethoprophos) and contamination amount (e.g., that of flutolanil, terbufos, and fenthion). In contrast, none of the contaminating pesticides were observed in the distilled spirits when a fermented liquefaction contaminated with 0.04-4 ppm of six pesticides (fenthion, terbufos, ethoprophos, iprobenfos, oxadiazon, and flutolanil) was distilled using a pilot-plant scale distillation column, indicating that the pesticides hardly migrate to the distilled spirits.
Assuntos
Bebidas Alcoólicas/análise , Contaminação de Alimentos/análise , Oryza/química , Resíduos de Praguicidas/análise , Anilidas/análise , Cádmio/análise , Destilação , Fention/análise , Fermentação , Chumbo/análise , Organotiofosfatos , Compostos Organotiofosforados/análise , Projetos PilotoRESUMO
A liquid chromatography-mass spectrometry assay was developed and validated for simultaneous quantification of anti-hormonal compounds abiraterone, anastrozole, bicalutamide, Δ(4)-abiraterone (D4A), N-desmethyl enzalutamide, enzalutamide, Z-endoxifen, exemestane and letrozole for the purpose of therapeutic drug monitoring (TDM). Plasma samples were prepared with protein precipitation. Analyses were performed with a triple quadrupole mass spectrometer operating in the positive and negative ion-mode. The validated assay ranges from 2 to 200â¯ng/mL for abiraterone, 0.2-20â¯ng/mL for D4A, 10-200â¯ng/mL for anastrozole and letrozole, 1-20â¯ng/mL for Z-endoxifen, 1.88-37.5â¯ng/mL for exemestane and 1500-30,000â¯ng/mL for enzalutamide, N-desmethyl enzalutamide and bicalutamide. Due to low sensitivity for exemestane, the final extract of exemestane patient samples should be concentrated prior to injection and a larger sample volume should be prepared for exemestane patient samples and QC samples to obtain adequate sensitivity. Furthermore, we observed a batch-dependent stability for abiraterone in plasma at room temperature and therefore samples should be shipped on ice. This newly validated method has been successfully applied for routine TDM of anti-hormonal drugs in cancer patients.
Assuntos
Antineoplásicos Hormonais , Monitoramento de Medicamentos/métodos , Administração Oral , Anastrozol/administração & dosagem , Anastrozol/análise , Androstadienos/administração & dosagem , Androstadienos/análise , Androstenos/administração & dosagem , Androstenos/análise , Anilidas/administração & dosagem , Anilidas/análise , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/análise , Benzamidas , Cromatografia Líquida de Alta Pressão , Humanos , Nitrilas/administração & dosagem , Nitrilas/análise , Feniltioidantoína/administração & dosagem , Feniltioidantoína/análogos & derivados , Feniltioidantoína/análise , Feniltioidantoína/metabolismo , Tamoxifeno/administração & dosagem , Tamoxifeno/análogos & derivados , Tamoxifeno/análise , Espectrometria de Massas em Tandem , Compostos de Tosil/administração & dosagem , Compostos de Tosil/análiseRESUMO
We have developed a simple and sensitive LC-MS/MS analytical method for the determination of residual flutolanil and its principal metabolites, including α,α,α-trifluoro-3'-hydroxy-o-toluanilide (M-4) and its conjugates, in livestock and seafood products. Both flutolanil and its metabolites contain the 2-(trifluoromethyl)benzoic acid (2-TFMBA) moiety. In this method, flutolanil and its metabolites are converted to 2-TFMBA by hydrolysis. The method involves direct hydrolysis with sodium hydroxide at 200°C, acidification, partitioning into a mixture of ethyl acetate-n-hexane (1:9, v/v), clean-up using a strong anion exchange cartridge (InertSep SAX), and then quantification using LC-MS/MS. The optimal conditions for the complete hydrolysis of flutolanil to 2-TFMBA are an incubation time of 6 h and a temperature of 200°C. The developed method was evaluated using seven types of food: bovine samples of muscle, fat, liver and milk, as well as egg, eel, and freshwater clam. Samples were spiked both at 0.01 mg/kg and at the Japanese maximum residue limit (MRL) established for each food type. The validation results show excellent recoveries (88-107%) and precision (< 10%) for flutolanil and M-4. The limit of quantification (S/N ≥ 10) of the developed method is 0.01 mg/kg. The developed method is applicable to the definition of residual flutolanil for animal-based food commodities and MRLs established by the Codex Alimentarius, and will be useful for the regulatory monitoring of residual flutolanil and its metabolites in food products.
Assuntos
Anilidas/análise , Anilidas/metabolismo , Análise de Alimentos , Leite/química , Óvulo/química , Resíduos de Praguicidas/análise , Alimentos Marinhos/análise , Animais , Bivalves , Bovinos , Cromatografia Líquida , Enguias , Resíduos de Praguicidas/metabolismo , Espectrometria de Massas em TandemRESUMO
Flutolanil and pentachloronitrobenzene (PCNB) are fungicides used to control or suppress foliar and soil borne diseases in turf and ornamental crops. On golf courses, sports fields, sod farms and commercial lawns these fungicides are used as preventive treatments to combat snow mold, brown patch and fairy ring. Depending on the aquatic organism, flultolanil and PCNB are considered to be moderately to highly toxic. Therefore runoff or drift from treated areas may be hazardous to organisms in adjacent aquatic sites. This research compared the transport of flutolanil and PCNB with runoff from turfgrass managed as a golf course fairway. The quantity of fungicide transported with runoff and observations reported with the chemographs followed trends in agreement with the chemical properties of the compounds. Overall, we observed the rate of transport for flutolanil was greater than PCNB, which contributed to the more than 12 times larger load (µg/m2) of flutolanil transported off-site at the conclusion of the simulated storm runoff. A better understanding of the off-site transport of pesticides with runoff is needed to make informed decisions on management practices to reduce potential adverse effects on non-target organisms, as well as maintain control of targeted pests in the area of application. In addition, data obtained with this research can be used in model simulations to predict nonpoint source pollution potentials beyond experimental conditions.
Assuntos
Agrostis , Anilidas/análise , Fungicidas Industriais/análise , Golfe , Nitrobenzenos/análise , Poluentes Químicos da Água/análise , Monitoramento AmbientalRESUMO
A laboratory experiment was conducted to investigate the effect of pH on the persistence and the dissipation of the new readymix formulation of bispyribac sodium and metamifop. The experiment was conducted in water of three different pH viz. 4.0, 7.0 and 9.2. The spiking level of both the compounds in water was 1.0 and 2.0 µg/mL. The residues were extracted by a simple, quick and reliable method and quantified by liquid chromatography tandem mass spectrometry (LC-MS/MS). The method was justified based on the recovery study, which was > 85%. The dissipation of both compounds followed first order kinetics. The half-life values ranged between 19.86-36.29 and 9.92-19.69 days for bispyribac sodium and metamifop, respectively. The pH of water has a prominent effect on degradation of both the compounds. The rate of dissipation of both the compounds was highest in water of acidic pH followed by neutral and alkaline pH.
Assuntos
Anilidas/análise , Benzoatos/análise , Benzoxazóis/análise , Herbicidas/análise , Pirimidinas/análise , Poluentes Químicos da Água/análise , Água/química , Cromatografia Líquida , Meia-Vida , Concentração de Íons de Hidrogênio , Cinética , Modelos Teóricos , Espectrometria de Massas em TandemRESUMO
Importance: Recent reports have described the increasing use of nonsteroidal selective androgen receptor modulators, which have not been approved by the US Food and Drug Administration (FDA), to enhance appearance and performance. The composition and purity of such products is not known. Objective: To determine the chemical identity and the amounts of ingredients in dietary supplements and products marketed and sold through the internet as selective androgen receptor modulators and compare the analyzed contents with product labels. Design and Setting: Web-based searches were performed from February 18, 2016, to March 25, 2016, using the Google search engine on the Chrome and Internet Explorer web browsers to identify suppliers selling selective androgen receptor modulators. The products were purchased and the identities of the compounds and their amounts were determined from April to August 2016 using chain-of-custody and World Anti-Doping Association-approved analytical procedures. Analytical findings were compared against the label information. Exposures: Products marketed and sold as selective androgen receptor modulators. Main Outcomes and Measures: Chemical identities and the amount of ingredients in each product marketed and sold as selective androgen receptor modulators. Results: Among 44 products marketed and sold as selective androgen receptor modulators, only 23 (52%) contained 1 or more selective androgen receptor modulators (Ostarine, LGD-4033, or Andarine). An additional 17 products (39%) contained another unapproved drug, including the growth hormone secretagogue ibutamoren, the peroxisome proliferator-activated receptor-δ agonist GW501516, and the Rev-ErbA agonist SR9009. Of the 44 tested products, no active compound was detected in 4 (9%) and substances not listed on the label were contained in 11 (25%). In only 18 of the 44 products (41%), the amount of active compound in the product matched that listed on the label. The amount of the compounds listed on the label differed substantially from that found by analysis in 26 of 44 products (59%). Conclusions and Relevance: In this limited investigation involving chemical analyses of 44 products marketed as selective androgen receptor modulators and sold via the internet, most products contained unapproved drugs and substances. Only 52% contained selective androgen receptor modulators and many were inaccurately labeled.
Assuntos
Anabolizantes/química , Comércio , Rotulagem de Medicamentos , Internet , Substâncias para Melhoria do Desempenho/química , Receptores Androgênicos , Acetamidas/análise , Aminofenóis/análise , Anilidas/análise , Aprovação de Drogas , Tráfico de Drogas , Nitrilas/análise , Pirrolidinas/análise , Estados Unidos , United States Food and Drug AdministrationRESUMO
Triafamone, a sulfamide herbicide, has been extensively utilized for weed control in rice paddies in Asia. However, its fate and transformation in the environment have not been established. Through a rice paddy microcosm-based simulation trial combined with multiple spectroscopic analyses, we isolated and identified three novel metabolites of triafamone, including hydroxyl triafamone (HTA), hydroxyl triafamone glycoside (HTAG), and oxazolidinedione triafamone (OTA). When triafamone was applied to rice paddies at a concentration of 34.2 g active ingredient/ha, this was predominantly distributed in the paddy soil and water, and then rapidly dissipated in accordance with the first-order rate model, with half-lives of 4.3-11.0 days. As the main transformation pathway, triafamone was assimilated by the rice plants and was detoxified into HTAG, whereas the rest was reduced into HTA with subsequent formation of OTA. At the senescence stage, brown rice had incurred triafamone at a concentration of 0.0016 mg/kg, but the hazard quotient was <1, suggesting that long-term consumption of the triafamone-containing brown rice is relatively safe. The findings of the present study indicate that triafamone is actively metabolized in the agricultural environment, and elucidation of the link between environmental exposure to these triazine or oxazolidinedione moieties that contain metabolites and their potential impacts is warranted.
Assuntos
Agricultura , Anilidas/análise , Herbicidas/análise , Poluentes do Solo/análise , Triazinas/análise , Ásia , Monitoramento Ambiental , Oryza/química , Solo/químicaRESUMO
An ultra-performance liquid chromatography with triple quadrupole mass spectrometry method was developed and validated for the determination of direct acting antiviral drug concentrations in human liver fine needle aspirates. Liver fine needle aspirate (FNA) biopsy samples were homogenized in acetonitrile to stabilize the analytes and precipitate protein. The acetonitrile supernatants were diluted with internal standards and mobile phase. Separation was achieved with a Waters Acquity BEH C18 column (50×2.1mm, 1.7um) with a gradient elution of 0.1% formic acid in water and acetonitrile. The total run time was 4.25min. Detection of analytes was achieved using electrospray ionization (positive mode) and triple quadrupole selected reaction monitoring. Standard curve concentrations ranged from 12.5 to 5000ng/mL for dasabuvir and the m1 metabolite of dasabuvir, 1.25 to 2500ng/mL for ombitasvir and ritonavir, and 5.00 to 5000ng/mL for paritaprevir. The intra- and inter-day accuracy and precision were less than 13.7% in low, medium, and high quality control samples. The validated method was applied to the analysis of a liver fine needle aspirate of a patient undergoing direct acting antiviral therapy for hepatitis C virus.
Assuntos
Anilidas/análise , Antivirais/análise , Carbamatos/análise , Cromatografia Líquida de Alta Pressão/métodos , Fígado/química , Compostos Macrocíclicos/análise , Sulfonamidas/análise , Espectrometria de Massas em Tandem/métodos , Uracila/análogos & derivados , 2-Naftilamina , Animais , Ciclopropanos , Humanos , Lactamas Macrocíclicas , Limite de Detecção , Agulhas , Prolina/análogos & derivados , Reprodutibilidade dos Testes , Uracila/análise , ValinaRESUMO
Besides their development for therapeutic purposes, non-steroidal selective androgen receptor modulators (non-steroidal SARMs) are also known to impact growth-associated pathways as ligands of androgenic receptors (AR). They present a potential for abuse in sports and food-producing animals as an interesting alternative to anabolic androgenic steroids (AAS). These compounds are easily available and could therefore be (mis)used in livestock production as growth promoters. To prevent such practices, dedicated analytical strategies should be developed for specific and sensitive detection of these compounds in biological matrices. The present study focused on Bicalutamide, a non-steroidal SARM used in human treatment of non-metastatic prostate cancer because of its anti-androgenic activity exhibiting no anti-anabolic effects. To select the most appropriate matrix to be used for control purposes, different animal matrices (urine and faeces) have been investigated and SARM metabolism studied to highlight relevant metabolites of such treatments and establish associated detection time windows. The aim of this work was thus to compare the urinary and faecal eliminations of bicalutamide in a calf, and investigate phase I and II metabolites. The results in both matrices showed that bicalutamide was very rapidly and mainly excreted under its free form. The concentration levels were observed as higher in faeces (ppm) than urine (ppb); although both matrices were assessed as suitable for residue control. The metabolites found were consistent with hydroxylation (phase I reaction) combined or not with glucuronidation and sulfation (phase II reactions). Copyright © 2016 John Wiley & Sons, Ltd.
Assuntos
Antagonistas de Androgênios/análise , Antagonistas de Androgênios/urina , Anilidas/análise , Anilidas/urina , Bovinos/urina , Fezes/química , Nitrilas/análise , Nitrilas/urina , Compostos de Tosil/análise , Compostos de Tosil/urina , Antagonistas de Androgênios/metabolismo , Anilidas/metabolismo , Animais , Bovinos/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Dopagem Esportivo , Nitrilas/metabolismo , Receptores Androgênicos/metabolismo , Detecção do Abuso de Substâncias/métodos , Espectrometria de Massas em Tandem/métodos , Compostos de Tosil/metabolismoRESUMO
The platensimycin (PTM) and platencin (PTN) class of natural products are promising drug leads that target bacterial and mammalian fatty acid synthases. Natural congeners and synthetic analogues of PTM and PTN have been instrumental in determining their structure-activity relationships, with only a few analogues retaining the potencies of PTM and PTN. Here we describe the identification and isolation of two new sulfur-containing PTM congeners (3 and 5) from the engineered dual PTM-PTN overproducing Streptomyces platensis SB12029. Structure elucidation of platensimycin D1 (5), a sulfur-containing PTM pseudo-dimer, revealed the existence of its presumptive thioacid precursor (3). The unstable thioacid 3 was isolated and confirmed by structural characterization of its permethylated product (6). LC-MS analysis of crude extracts of SB12029 confirmed the presence of the thioacid analogue of PTN (4). The minimum inhibitory concentration (MIC) was determined for 5 revealing retention of the strong antibacterial activity of PTM.
Assuntos
Adamantano/farmacologia , Aminobenzoatos/farmacologia , Aminofenóis/farmacologia , Anilidas/farmacologia , Antibacterianos/farmacologia , Produtos Biológicos/farmacologia , Compostos Policíclicos/farmacologia , Streptomyces/química , Enxofre/farmacologia , Adamantano/análise , Aminobenzoatos/análise , Aminofenóis/análise , Anilidas/análise , Antibacterianos/análise , Produtos Biológicos/análise , Testes de Sensibilidade Microbiana , Micrococcus luteus/efeitos dos fármacos , Compostos Policíclicos/análise , Staphylococcus aureus/efeitos dos fármacos , Enxofre/análiseRESUMO
Direct HPLC separation of enantiomers of Bicalutamide (BCT), a non-steroidal antiandrogen used for the treatment of prostate cancer, was performed by using the immobilized amylose-based Chiralpak IA chiral stationary phase (CSP). Enantioselective conditions were achieved using standard normal phase mixtures n-hexane-alcohol (ethanol or 2-propanol) and a "non-standard" mobile phase containing ethyl acetate (EA). The chromatographic behaviour of the IA CSP under these elution modes was evaluated and compared at different temperatures. The eluent mixture n-hexane-EA-ethanol 100-30-5 (v/v/v) and the column temperature of 40°C were identified as the best operational conditions to carry out semipreparative enantioseparations on a 1-cm I.D. IA column. Using this protocol, about 960mg of (R)-BCT, which is the enantiomer with the almost entire anti-androgenic activity of BCT, per day could be isolated. The analytical and semipreparative HPLC resolution of chiral impurities of BCT, and their empiric absolute configuration assignment by circular dichroism correlation method are also presented.
Assuntos
Anilidas/análise , Técnicas de Química Analítica/métodos , Cromatografia Líquida de Alta Pressão , Nitrilas/análise , Polissacarídeos/química , Compostos de Tosil/análise , 2-Propanol/química , Amilose/química , Anilidas/química , Dicroísmo Circular , Etanol/química , Hexanos/química , Nitrilas/química , Estereoisomerismo , Compostos de Tosil/químicaRESUMO
A method for the determination of ipfencarbazone in agricultural products, livestock products and seafood by LC-MS/MS was developed. Agricultural samples were extracted with acetone. An aliquot of crude extract was partitioned with n-hexane and sat. sodium chloride solution. Clean-up was performed using GC/PSA and C18 cartridges. In the case of livestock products and seafood, samples were extracted with a mixture of acetone and n-hexane, and the organic layer was collected. After acetonitrile-hexane partitioning, the extract was cleaned up using PAS and C18 cartridges. The gradient LC separation was performed on a C18 column with acetonitrile-water containing acetic acid as a mobile phase, and MS with positive ion electrospray ionization was used for detection. The average recoveries (n=5) of ipfencarbazone from 16 kinds of agricultural products, livestock products and seafood spiked at the MRLs or at the uniform limits (0.01 ppm) were 73-101%, and the relative standard deviations were 1.3-5.1%. The limit of quantitation of the developed method was 0.01 mg/kg for ipfencarbazone.
Assuntos
Anilidas/análise , Cromatografia Líquida/métodos , Produtos Agrícolas/química , Análise de Alimentos/métodos , Contaminação de Alimentos/análise , Herbicidas/análise , Produtos da Carne/análise , Alimentos Marinhos/análise , Espectrometria de Massas em Tandem/métodos , Triazóis/análise , Anilidas/química , Animais , Ovos/análise , Leite/química , Triazóis/químicaRESUMO
Bicalutamide is a non-steroidal anti-androgen drug used for the treatment of androgen-dependent prostate cancer. Hesperetin is a natural bioflavonoid that can be used in combination with bicalutamide to improve efficacy and decrease tolerance. The aim of the present work was to develop and validate a simple, sensitive, rapid reverse phase-high performance liquid chromatographic method for simultaneous estimation of bicalutamide and hesperetin. The validation parameters such as specificity, linearity, precision and accuracy, limit of detection (LOD) and limit of quantification (LOQ) were determined according to International Conference on Harmonization ICH Q2 (R1) guidelines. Chromatographic separation was achieved on Lichrocart(®) CN column (250 × 4 mm, 5 µm, MERCK) with isocratic elution. The retention times and detection wavelength, for hesperetin and bicalutamide were 4.28 min, 288 nm and 5.90 min, 270 nm respectively. The intra-day and inter-day assay precision and accuracy were found to be <2% over linearity of 50-2000 ng/mL with R(2) 0.999. LOD and LOQ, of bicalutamide and hesperetin was 14.70, 44.57 ng/mL and 16.11, 48.84 ng/mL, respectively. The method was successfully applied for encapsulation efficiency and drug release studies from bicalutamide and hesperetin loaded nanoparticles.
Assuntos
Anilidas/análise , Quitosana/química , Cromatografia Líquida de Alta Pressão/métodos , Hesperidina/análise , Nanopartículas/química , Nitrilas/análise , Poliésteres/química , Compostos de Tosil/análise , Anilidas/química , Antineoplásicos/análise , Antineoplásicos/química , Cromatografia de Fase Reversa/métodos , Hesperidina/química , Limite de Detecção , Modelos Lineares , Nitrilas/química , Reprodutibilidade dos Testes , Compostos de Tosil/químicaRESUMO
Sexual disruption in wild fish has been linked to the contamination of river systems with steroid oestrogens, including the pharmaceutical 17α-ethinylestradiol, originating from domestic wastewaters. As analytical chemistry has advanced, more compounds derived from the human use of pharmaceuticals have been identified in the environment and questions have arisen as to whether these additional pharmaceuticals may also impact sexual disruption in fish. Indeed, pharmaceutical anti-androgens have been shown to induce such effects under laboratory conditions. These are of particular interest since anti-androgenic biological activity has been identified in the aquatic environment and is potentially implicated in sexual disruption alone and in combination with steroid oestrogens. Consequently, predictive modelling was employed to determine the concentrations of two anti-androgenic human pharmaceuticals, bicalutamide and cyproterone acetate, in UK sewage effluents and river catchments and their combined impacts on sexual disruption were then assessed in two fish models. Crucially, fish were also exposed to the anti-androgens in combination with steroid oestrogens to determine whether they had any additional impact on oestrogen induced feminisation. Modelling predicted that the anti-androgenic pharmaceuticals were likely to be widespread in UK river catchments. However, their concentrations were not sufficient to induce significant responses in plasma vitellogenin concentrations, secondary sexual characteristics or gross indices in male fathead minnow or intersex in Japanese medaka alone or in combination with steroid oestrogens. However, environmentally relevant mixtures of oestrone, 17ß-oestradiol and 17α-ethinylestradiol did induce vitellogenin and intersex, supporting their role in sexual disruption in wild fish populations. Unexpectedly, a male dominated sex ratio (100% in controls) was induced in medaka and the potential cause and implications are briefly discussed, highlighting the potential of non-chemical modes of action on this endpoint.
Assuntos
Antagonistas de Androgênios/toxicidade , Anilidas/toxicidade , Acetato de Ciproterona/toxicidade , Nitrilas/toxicidade , Rios/química , Desenvolvimento Sexual/efeitos dos fármacos , Compostos de Tosil/toxicidade , Antagonistas de Androgênios/análise , Anilidas/análise , Animais , Cyprinidae/fisiologia , Acetato de Ciproterona/análise , Transtornos do Desenvolvimento Sexual/induzido quimicamente , Estradiol/toxicidade , Estrogênios/toxicidade , Etinilestradiol/análise , Etinilestradiol/toxicidade , Masculino , Nitrilas/análise , Oryzias/fisiologia , Esgotos/química , Compostos de Tosil/análise , Vitelogeninas/sangue , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
A rapid and highly sensitive assay method has been developed and validated for the estimation of bicalutamide (BCL) on mouse dried blood spots (DBS) using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the negative-ion mode. The assay procedure involves a simple liquid extraction of BCL and tolbutamide (internal standard, IS) from mouse blood DBS cards using tert-butyl methyl ether. Chromatographic separation was achieved with 5 mm ammonium acetate (pH 6.5)-acetonitrile (35:65, v/v) at a flow rate of 0.60 mL/min on an Atlantis dC18 column with a total run time 3.0 min. The MS/MS ion transitions monitored were 428.80 â 254.70 for BCL and 269.00 â 169.60 for IS. Method validation was performed as per regulatory guidelines. A linear response function was observed from 0.92 to 1911 ng/mL for BCL in mouse blood. The intra- and inter-day precisions were in the ranges of 1.86-12.5 and 3.19-10.8%, respectively. This novel DBS method has been applied to a pharmacokinetic study in mice.
Assuntos
Anilidas/análise , Cromatografia Líquida/métodos , Nitrilas/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Compostos de Tosil/análise , Animais , CamundongosRESUMO
A reliable and rapid method has been optimized to determine the residue of amicarthiazol in soil and environmental water samples. After extraction and evaporation, the extraction was carried out with solid phase extraction (SPE) cleanup using HLB cartridge (only soil samples) and for the quantitative determination by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The resulting residues of amicarthiazol were analyzed by a gradient separation performed on a UPLC system with a C18 column, methanol and water containing 0.1% (v v(-1)) formic acid as the mobile phase in the mode of electrospray positive ionization (ESI(+)) and multiple reaction monitoring (MRM). Results showed that the recoveries for spiked samples were 74.4-97.1% and 72.1-109.9% for soil and water, respectively, with the relative standard deviation (RSD) less than 10.2% when fortified at 10, 100 and 1000µgL(-1). The limits of detection (LODs) and the limits of quantification (LOQs) for matrix matched standards ranged from 0.073-0.425µgL(-1) and 0.243-1.42µgL(-1). The intra-day precision (n=5) and the inter-day precision over 10 days (n=10) for the amicarthiazol in soils and water samples spiked at 100µgL(-1) was 7.9% and 15.9%, respectively. Results indicated that the developed method could be a helpful tool for the controlling and monitoring of the risks posed by amicarthiazol to human health and environment safety.