Proton-transfer compounds with 4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide (sulfamethazine): the structures and hydrogen-bonding in the salts with 5-nitrosalicylic acid and picric acid

The structures of the anhydrous proton-transfer compounds of the sulfa drug sulfamethazine with 5-nitrosalicylic acid and picric acid, namely 2-(4-aminobenzenesulfonamido)-4,6-dimethylpyrimidinium 2-hydroxy-5-nitrobenzoate, C12H15N4O2S(+)·C7H4NO4(-), (I), and 2-(4-aminobenzenesulfonamido)-4,6-dimethylpyrimidinium 2,4,6-trinitrophenolate, C12H15N4O2S(+)·C6H2N3O7(-), (II), respectively, have been determined. In the asymmetric unit of (I), there are two independent but conformationally similar cation-anion heterodimer pairs which are formed through duplex intermolecular N(+)-H...Ocarboxylate and N-H...Ocarboxylate hydrogen-bond pairs, giving a cyclic motif [graph set R2(2)(8)]. These heterodimers form separate and different non-associated substructures through aniline N-H...O hydrogen bonds, one one-dimensional, involving carboxylate O-atom acceptors, the other two-dimensional, involving both carboxylate and hydroxy O-atom acceptors. The overall two-dimensional structure is stabilized by π-π interactions between the pyrimidinium ring and the 5-nitrosalicylate ring in both heterodimers [minimum ring-centroid separation = 3.4580 (8) Å]. For picrate (II), the cation-anion interaction involves a slightly asymmetric chelating N-H...O R2(1)(6) hydrogen-bonding association with the phenolate O atom, together with peripheral conjoint R1(2)(6) interactions between the same N-H groups and O atoms of the ortho-related nitro groups. An inter-unit amine N-H...Osulfone hydrogen bond gives one-dimensional chains which extend along a and inter-associate through π-π interactions between the pyrimidinium rings [centroid-centroid separation = 3.4752 (9) Å]. The two structures reported here now bring to a total of four the crystallographically characterized examples of proton-transfer salts of sulfamethazine with strong organic acids.

Biosensor assay of sulfadiazine and sulfamethazine residues in pork

Biosensor-based immunochemical screening assays for the detection of sulfadiazine (SDZ) and sulfamethazine (SMT) in muscle extract from pigs were developed. Samples were extracted with aqueous buffer and then centrifuged. This simple and straightforward preparation allowed up to 40 samples to be processed and analysed in 1 d. The limits of detection for the assays were found to be 5.6 ng g(-1) for SDZ and 7.4 ng g(-1) for SMT. These figures were well below the European and US legal limits for sulfonamides (100 ng g(-1)). The precision (RSD) between runs was

Evaluation of an immunobiosensor for the on-site testing of veterinary drug residues at an abattoir. Screening for sulfamethazine in pigs

A study was conducted to determine the feasibility of performing

4-Amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide-4-nitrobenzoic acid

In the asymmetric unit of the title co-crystal, C12H14N4O2S . C7H5NO4 there are two independent but conformationally similar heterodimers, which are formed through intermolecular N-H...O(carboxy) and carboxyl O-H...N hydrogen-bond pairs, giving a cyclic motif [graph set R2/2(8)]. The dihedral angles between the rings in the sulfonamide molecules are 78.77(8) and 82.33(9)deg. while the dihedral angles between the ring and the CO2H group in the acids are 2.19(9) and 7.02(10)deg. A two-dimensional structure parallel to the ab plane is generated from the heterodimer units through hydrogen-bonding associations between NH2 and sulfone groups. Between neighbouring two-dimensional arrays there are two types of aromatic pi-pi stacking interactions involving either one of the pyrimidine rings and a 4-nitrobenzoic acid molecule [minimum ring centroid separation = 3.5886(9)A] or two acid molecules [minimum ring centroid separation = 3.7236(10)A].

4-Amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide--2-nitrobenzoic acid (1/1)

In the asymmetric unit of the title co-crystal, C12H14N4O2S·C7H5NO4, the sulfamethazine and 2-nitrobenzoic acid molecules form a heterodimer through intermolecular amide-carboxylic acid N-HO and carboxylic acid-pyrimidine O-HN hydrogen-bond pairs, giving a cyclic motif [graph set R22(8)]. The dihedral angle between the two aromatic ring systems in the sulfamethazine molecule is 88.96 (18)° and the nitro group of the acid is 50% rotationally disordered. Secondary aniline N-HOsulfone hydrogen-bonding associations give a two-dimensional structure lying parallel to the ab plane.

2-(4-Aminobenzenesulfonamido)-4,6-dimetylpyrimidin-1-ium 2-carboxy-4,6-dinitrophenolate

In the structure of the of the phenolate salt of the sulfa drug sulfamethazine with 3,5-dinitrosalicylic acid, C12H15N4O2S+ C7H3N2O7-, the dihedral angle between the pyrimidine and phenyl rings of the cation is 59.70(17)\%. Cation--anion hydrogen-bonding interactions involving pyrimidine N+-H...O(carboxyl) and amine N-H...O(carboxyl) pairs give a cyclic R2/2(8) motif while secondary N-H...O hydrogen bonds between the aniline group and both sulfone and nitro O-atom acceptors give a two-dimensional structure extending along (001).

A competitive enzyme-linked immunosorbent assay for determination of chloramphenicol

Chloramphenicol is a broad-spectrum antibiotic shown to have specific activity against a wide variety of organisms that are causative agents of several disease conditions in domestic animals. Chloramphenicol has been banned for use in food-producing animals for its serious adverse toxic effects in humans. Due to the harmful effects of chloramphenicol residues livestock products should be free of any traces of these residues. Several analytical methods are available for chloramphenicol analysis but sensitive methods are required in order to ensure that no traces of chloramphenicol residues are present in edible animal products. In order to prevent the illegal use of chloramphenicol, regulatory control of its residues in food of animal origin is essential. A competitive enzyme-linked immunosorbent assay for chloramphenicol has been locally developed and optimized for the detection of chloramphenicol in sheep serum. In the assay, chloramphenicol in the test samples and that in chloramphenicol-horseradish peroxidase conjugate compete for antibodies raised against the drug in camels and immobilized on a microtitre plate. Tetramethylbenzidine-hydrogen peroxide (TMB/H2O2) is used as chromogen-substrate system. The assay has a detection limit of 0.1 ng/mL of serum with a high specificity for chloramphenicol. Cross-reactivity with florfenicol, thiamphenicol, penicillin, tetracyclines and sulfamethazine was not observed. The assay was able to detect chloramphenicol concentrations in normal sheep serum for at least 1 week after intramuscular injection with the drug at a dose of 25 mg/kg body weight (b.w.). The assay can be used as a screening tool for chloramphenicol use in animals.

Comparison of porcine urine and bile as matrices to screen for the residues of two sulfonamides using a semi-automated enzyme immunoassay.

Porcine urine enzyme immunoassays for sulfamethazine and sulfadiazine have previously been employed as screening tests to predict the concentrations of the drugs in the corresponding tissues (kidneys), If a urine was found positive (> 800 ng ml(-1)) the corresponding kidney was then analysed by an enzyme immunoassay and, if found positive, a confirmatory analysis by HPLC was performed. Urine was chosen as the screening matrix since sulfonamides are mainly eliminated through this body fluid, However, after obtaining a number of false positive predictions, an investigation was carried out to assess the possibility of using an alternative body fluid which would act as a superior indicator of the presence of sulfonamides in porcine kidney, An initial study indicated that serum, plasma and bile could all be used as screening matrices. From these, bile was chosen as the preferred sample matrix and an extensive study followed to compare the efficiencies of sulfonamide positive bile and urine at predicting sulphonamide positive kidneys, Bile was found to be 17 times more efficient than urine at predicting a sulfamethazine positive kidney and 11 times more efficient at predicting a sulfadiazine positive kidney, With this enhanced performance of the initial screening test, the need for the costly and time consuming kidney enzyme immunoassay, prior to HPLC analysis, was eliminated

Multi sulfonamide screening in porcine muscle using a surface plasmon resonance biosensor

A binding protein displaying broad-spectrum cross-reactivity within the sulfonamide group was used in conjunction with a sulfonamide specific sensor chip and a surface plasmon resonance biosensor to develop a rapid broad spectrum screening assay for sulfonamides in porcine muscle. Results for 40 samples were available in just over 5 h after the completion of a simple sample preparation protocol. Twenty sulfonamide compounds were detected. Acetylated metabolites were not recognised by the binding protein. Limit of detection (mean-three times standard deviation value when n = 20) was calculated to be 16.9 ng g(-1) in tissue samples. Intra-assay precision (n = 10) was calculated at 4.3 %CV for a sample spiked at 50 ng g(-1) with sulfamethazine, 3.6 %CV for a sample spiked at 100 ng g(-1) with sulfamethazine, 7.2 %CV for a sample spiked at 50 ng g(-1) with sulfadiazine and 3.1 %CV for a sample spiked at 100 ng g-1 with sulfadiazine. Inter-assay precision (n = 3) was calculated at 9.7 %CV for a sample spiked at 50 ng g-1 with sulfamethazine, 3.8 %CV for a sample spiked at 100 ng g(-1) with sulfamethazine, 3.5 %CV for a sample spiked at 50 ng g(-1) with sulfadiazine and 2.8 %CV for a sample spiked at 100 ng g(-1) with sulfadiazine. (C) 2004 Elsevier B.V. All rights reserved.

Motorização de fármacos na água bruta e na água para consumo humano por cromatolografia líquida de ultra eficiência associada à espectrometria de massa tandem

Tese de doutoramento, Farmácia (Bromatologia), Universidade de Lisboa, Faculdade de Farmácia, 2014

Determination of Tetracycline in Environmental Water Samples at a Graphite-Polyurethane Composite Electrode

A bare graphite-polyurethane composite was evaluated in the tetracycline (TC) determination in natural water samples. Using differential pulse voltammetry (DPV), a linear response was observed in the range of 4.00-40.0 mu mol L-1 with limit of detection of 2.80 mu mol L-1, without the need of surface renewing between successive runs. During the tetracycline determination in water samples, recoveries between 92.6 and 100% were found. The results for TC determination in water samples after a pre-concentration stage agreed with spiked value at a 95% confidence level according to student t-test.

Espectroscopia no infravermelho e método quimiométrico para a pesquisa de antimicrobianos em leite da microrregião de Pato Branco - PR

Considering the social and economic importance that the milk has, the objective of this study was to evaluate the incidence and quantifying antimicrobial residues in the food. The samples were collected in dairy industry of southwestern Paraná state and thus they were able to cover all ten municipalities in the region of Pato Branco. The work focused on the development of appropriate models for the identification and quantification of analytes: tetracycline, sulfamethazine, sulfadimethoxine, chloramphenicol and ampicillin, all antimicrobials with health interest. For the calibration procedure and validation of the models was used the Infrared Spectroscopy Fourier Transform associated with chemometric method based on Partial Least Squares regression (PLS - Partial Least Squares). To prepare a work solution antimicrobials, the five analytes of interest were used in increasing doses, namely tetracycline from 0 to 0.60 ppm, sulfamethazine 0 to 0.12 ppm, sulfadimethoxine 0 to 2.40 ppm chloramphenicol 0 1.20 ppm and ampicillin 0 to 1.80 ppm to perform the work with the interest in multiresidues analysis. The performance of the models constructed was evaluated through the figures of merit: mean square error of calibration and cross-validation, correlation coefficients and offset performance ratio. For the purposes of applicability in this work, it is considered that the models generated for Tetracycline, Sulfadimethoxine and Chloramphenicol were considered viable, with the greatest predictive power and efficiency, then were employed to evaluate the quality of raw milk from the region of Pato Branco . Among the analyzed samples by NIR, 70% were in conformity with sanitary legislation, and 5% of these samples had concentrations below the Maximum Residue permitted, and is also satisfactory. However 30% of the sample set showed unsatisfactory results when evaluating the contamination with antimicrobials residues, which is non conformity related to the presence of antimicrobial unauthorized use or concentrations above the permitted limits. With the development of this work can be said that laboratory tests in the food area, using infrared spectroscopy with multivariate calibration was also good, fast in analysis, reduced costs and with minimum generation of laboratory waste. Thus, the alternative method proposed meets the quality concerns and desired efficiency by industrial sectors and society in general.