Stability of 5-aminosalicylic acid and its metabolites in plasma at -20 degrees C. Formation of N-beta-D-glucopyranosyl-5-aminosalicylic acid.

The stability of 5-aminosalicylic acid and its metabolites has been investigated when stored frozen. N-beta-D-Glucopyranosyl-5-aminosalicylic acid was formed in considerable amounts concomitant with a decrease in 5-aminosalicylic acid in plasma samples spiked with 5-aminosalicylic acid as well as in standard solutions of 5-aminosalicylic acid buffered with potassium phosphate between pH 5.5 and pH 8.0 with 4.0 mM glucose added and stored at -20 degrees C. Thus N-beta-D-glucopyranosyl-5-aminosalicylic acid might not, as previously described, be a metabolite of 5-aminosalicylic acid but an artifact formed during storage of plasma samples. The N-glucoside formed could be quantitatively degraded to 5-aminosalicylic acid and glucose by adding 0.2 M potassium phosphate buffer pH 3.0 to the sample prior to the analysis. The metabolites of 5-aminosalicylic acid (N-formyl-5-aminosalicylic acid, N-acetyl-5-aminosalicylic acid and N-butyryl-5-aminosalicylic acid) were found to be stable in plasma stored at -20 degrees C for at least eight months.     

Thermal studies on mixtures of aminosalicylic acids with cyclodextrins

The thermal behaviour of the aminosalicylic acids is compared with the behaviour of their 1:1 molar ratio physical and kneaded mixtures with each of three different cyclodextrins (b-, hydroxypropyl-b-, and g-cyclodextrin), using differential scanning calorimetry and thermogravimetry coupled with evolved gas analysis by Fourier transform infrared spectroscopy. X-ray powder diffraction and infrared spectroscopy provided complementary information. Comparison of the effects of the different cyclodextrins on the behaviour of the individual aminosalicylic acid isomers shows that hydroxypropyl-b-cyclodextrin has the greatest interaction with 3-aminosalicylic acid and 5-aminosalicylic acid, followed by g-cyclodextrin, while b-cyclodextrin generally shows the least interaction. For 4-aminosalicylic acid, the effect of g-cyclodextrin seems to be more marked than for 3-aminosalicylic acid and 5-aminosalicylic acid. This revised version was published online in July 2006 with corrections to the Cover Date.     

Thermal studies on the sodium salts of aminosalicylic acids

The effect on the stability of the isomers of aminosalicylic acid of formation of their sodium salts has been studied by use of differential scanning calorimetry and thermogravimetry, coupled with evolved gas analysis by Fourier transform infrared spectroscopy. X-ray powder diffraction and infrared spectroscopy provided complementary information. The DSC curves for the sodium salts of all of the isomers showed complex dehydration/decomposition endotherms. From the initial mass losses of the TG curves, the amounts of water per mole of salt were estimated as 0.5, 2.4 and 1.4 moles for the sodium salts of 3-aminosalicylic acid, 4-aminosalicylic acid and 5-aminosalicylic acid, respectively. TG-FTIR results for the sodium salt of 3-aminosalicylic acid showed the evolution of carbon dioxide in three stages: below 150°C, between 200 and 300°C and continuous formation up to 500°C. This behaviour differs from that of 3-aminosalicylic acid itself, which forms CO₂ between 225 and 290°C. For the sodium salt of 4-aminosalicylic acid, the formation of carbon dioxide starts from 250°C and is still being formed at about 650°C. 4-aminosalicylic acid decarboxylates above 150°C. 5-aminosalicylic acid and its sodium salt showed no evolution of carbon dioxide below 600°C. This revised version was published online in July 2006 with corrections to the Cover Date.     

Modelling the thermal behaviour of carboxylic acid derivatives with cylcodextrins in the solid-state

The application of classical QSAR and molecular modelling to the inclusion complexation of natural and modified cyclodextrins (CDs) with carboxylic acid derivatives as guest molecules was examined. Information was available on the thermal behaviour, in the solid-state of benzoic acid (BA), salicylic acid (SA), and various substituted aminosalicylic acids (3-aminosalicylic acid, 3-ASA, 4-aminosalicylic acid, 4-ASA and 5-aminosalicylic acid, 5-ASA), as well as on the thermal behaviour of 1:1 molar ratio physical and kneaded mixtures of these acids with each of three different cyclodextrins, β-, (BCD) 2-hydroxypropyl-β-, (HPBCD) and γ-cyclodextrin (GCD). The thermal behaviour of the binary (1:1 stoichiometry) mixtures was modelled using stepwise multiple regression (SMR). Two models for the prediction of the percentage mass loss and enthalpy of dehydration of the physical mixtures were established with correlation coefficients (r) of 0.79 and 0.92, respectively. Decreased correlation in the thermal behaviour of kneaded mixtures indicated significant interaction and possible formation of inclusion complexes. This revised version was published online in July 2006 with corrections to the Cover Date.     

Facilitated transport of 5-aminosalicylic acid through bulk liquid membrane

This paper describes the experimental results obtained at the transport of 5-aminosalicylic acid (5ASA) through agitated bulk liquid membrane, using Aliquat 336, as carrier, dissolved in a chloroform membrane. The influence of 5-aminosalicylic acid concentration in the feed source, HCl concentration in the stripping phase and carrier (Aliquat 336) concentration in the membrane were investigated. The optimal pH condition of feed source was established based on the speciation diagram of 5-aminosalicylic acid. The assessment of the transport process was performed by determining the kinetic parameters—mass transfer coefficient and entrance and exist flow in and out of the chloroform membrane.     

Synthesis of 4-Aminosalicylglycine

To search for a better prodrug of 4-aminosalicylic acid that is expected to deliver stably parent drug to colon against the inflammatory bowel disease, a novel 4-aminosalicylic acid derivative was designed and synthesized from 4-aminosalicylic acid. 4-Aminosalicylglycine was prepared from 4-aminosalicylic acid by protecting amino and hydroxyl groups with benzyloxycarbonyl and acetyl, respectively, then the carboxylic acid was converted to acyl chloride which was treated with glycine. After removing the protection groups, 4-aminosalicylglycine wasobtained. All the compounds were characterized by FT-IR, ^1H-NMR, ^13C-NMR spectra. In vivo experiment on rats suggested that the curative effect of 4-aminosalicylglycine was more effective than that of 4-aminosalicylic acid.     

高分子药物研究Ⅰ．5－氨基水杨酸与二元羧酸缩聚物的合成

通过５－氨基水杨酸与二元羧酸进行缩聚反应，合成了六种主链含有５－氨基水杨酸的高分子化合物，用红外光谱和元素分析确定了聚合物的结构。聚合物水解实验表明，它们在酸性、中性和碱性介质中均能水解，水解速率（ｒ）的大小依次为ｒｐＨ＝１３．０＞ｒｐＨ＝７．０＞ｒｐＨ＝２．０。     

5-氨基水杨酸锌及相关物质的高效液相色谱分析研究

对５－氨基水杨酸锌及相关物质５－氨基水杨酸、水杨酸、对氨基苯酚和５－苯偶氮基水杨酸的高效液相色谱法（ＨＰＬＣ）的分离条件进行了优化研究,结果表明,采用ＣＬＣ－ＯＤＳ（１５０ｍｍ×６．０ｍｍｉ．ｄ．,１０μｍ）作为分离柱,１％（Ｖ／Ｖ）ＨＡｃ－ＭｅＯＨ（４∶６）作为流动相,在流速为１ｍＬ／ｍｉｎ的情况下,上述５种物质在１０ｍｉｎ内可以达到基线分离,保留时间的日内和日间的变异系数分别小于２％和５％,在一定浓度范围内,浓度与峰面积的线性关系良好。     

Thermal Studies on Some Substituted Aminobenzoic Acids

The thermal behaviour of various substituted aminobenzoic acids(3-aminobenzoic acid (3-ABA), 4-aminobenzoic acid (4-ABA), 3-aminosalicylic acid(3-ASA), 4-aminosalicylic acid (4-ASA), and 5-aminosalicylic acid (5-ASA), as well as the‘parent’ benzoic acid (BA) and salicylic acid (SA) as reference substances, and possible decomposition products: 2-aminophenol (2-AP), 3-aminophenol (3-AP) and 4-aminophenol(4-AP) in the solid state has been examined. The various sets of isomers studied showed considerable and interesting differences. Most sublimed well before melting, generally with an increasing rate of mass loss beyond their very different melting points. The differences in behaviour of 4-ASA and 5-ASA were the most remarkable, with 5-ASA being far more stable and apparently not decarboxylating readily, while 4-ASA sublimed at temperatures below the melting point, becoming less stable and decarboxylating in the liquid form. This revised version was published online in July 2006 with corrections to the Cover Date.     

七元瓜环作为5-氨基水杨酸结肠给药载体可行性考察

利用荧光光谱法考察了七元瓜环(Q[7])和5-氨基水杨酸(5-ASA)在不同pH条件下的相互作用. 在pH＝2.0, 4.0时, Q[7]与5-ASA可形成1∶1(物质的量比)的包合物; 而在pH＝5.0, 6.0, 7.4 时未观察到两者之间有明显的相互作用. 利用¹H NMR 技术研究了Q[7]-5-ASA固体包合物不同pH值的存在形式. 当体系的pH＜6.0, 5-ASA以包合物的形式存在. 而当pH＞6.0, 包合物的稳定性下降, 5-ASA被释放出来以游离的药物分子形式存在, 说明5-ASA与Q[7]之间的相互作用依赖于体系的pH值, Q[7]可作为5-ASA结肠给药的一种潜在载体; 热动力学的研究表明包合作用主要受到体系焓变的影响; 红外光谱, DSC和TG的分析进一步证实了Q[7]-5-ASA固体包合物的形成.     

Aminosalicylic acid conjugates of EDTA as potential anti-inflammatory pro-drugs: synthesis,copper chelation and superoxide dismutase-like activities

Aminosalicylic acids have been used to combat inflammatory bowel diseases (IBDs) for over 60 years. In this report, spectroscopic studies on the Cu(II) complexation behaviour of the newly synthesised chelator ethylenediaminetetraacetic acid bis-(4-aminosalicylic acid methyl ester) (4-EBAME), and the regiostereoisomer ethylenediaminetetraacetic acid bis-(5-aminosalicylic acid methyl ester) (5-EBAME) are presented. Both conjugates bind to Cu(II) in an ideal 1:1 ratio, as shown by Job’s method and spectroscopic titrations. 5-EBAME was screened in the NCI 60 cancer cell-line and showed anti-cancer properties. Neither of the conjugates were degraded by bovine liver protease, although some de-esterification was seen at high pH over a 24-h period. These two conjugates show potential as metal chelating anti-oxidants for use against IBDs.     

Sonoelectrochemically enhanced determination of 5-aminosalicylic acid

The electrochemical detection of the anti-inflammatory drug 5-aminosalicylic acid (5-ASA) has been evaluated through the application of linear sweep, square wave and sonolinear sweep voltammetry. The introduction of ultrasound is shown to significantly enhance the oxidation signal intensity thereby enabling the detection of low concentrations with the linear range (1-57 muM) adequate for assessing free drug within physiological samples. Interference from ascorbic acid can be effectively negated through the introduction of cupric ion without any appreciable cost to the voltammetric response to 5-ASA. The efficacy of employing sonolinear sweep voltammetry to the determination of this compound within a compositionally complex tissue culture medium has been assessed with the recovery of 5 muM 5-ASA found to be 102% (RSD=5%, N=3).     

Simple and rapid method for the simultaneous determination of the eight main metabolites and conjugates of sulphasalazine in human plasma, urine and faeces using dynamically modified silica

A simple and rapid method for the simultaneous determination of sulphapyridine, N-acetylsulphapyridine, 5-aminosalicylic acid, N-acetyl-5-aminosalicylic acid, hydroxysulphapyridine, N-acetylhydroxysulphapyridine, sulphapyridine O-glucuronide and N-acetylsulphapyridine O-glucuronide in plasma, urine and faeces is presented. After precipitation of plasma proteins by addition of methanol the samples are injected directly into the liquid chromatographic system. The limit of detection is 1 microgram/ml or less at a signal-to-noise ratio of 5 for all compounds using ultraviolet, fluorescence or electrochemical detection. The advantages of the dynamically modified silica approach in this reversed-phase high-performance liquid chromatographic method are demonstrated with respect to regulation and reproducibility of the selectivity.     

水杨酸功能化聚苯乙烯的制备及其与铕(Ⅲ)离子配合物荧光特性研究

以氯甲基聚苯乙烯(CMPS)为出发物质,通过两步改性反应,相转移催化的酯化反应(乙醛酸钠为反应试剂)与均相的Schiff碱反应,制备了侧链键合水杨酸(ASA)配基的聚苯乙烯ASAPS,并使之与Eu(Ⅲ)离子配位螯合,制备了高分子-稀土配合物ASAPS-Eu(Ⅲ).重点研究了相转移催化的酯化反应,也初步考察了配合物ASAPS-Eu(Ⅲ)的发光性能.研究结果表明,在季铵盐相转移催化剂作用下,溶解于有机溶剂中的CMPS可有效地与水相中的乙醛酸钠发生酯化反应,形成醛基(AL)化改性的聚苯乙烯ALPS.相转移催化剂的结构与溶剂的极性对相转移催化反应有显著的影响;配合物ASAPS-Eu(Ⅲ)具有Eu(Ⅲ)的特征荧光发射,并产生显著的Antenna效应.     

Interaction of Siberian larch arabinogalactan with amino-containing compounds

The interaction of the natural polysaccharide arabinogalactan and its oxidized fractions with 5-aminosalicylic acid, 4-aminosalicylic acid, and isonicotinic acid hydrazide in aqueous solutions is investigated with the use of physicochemical methods. The compositions and stability constants of the formed complexes are studied, and the optimal conditions of their preparation are found. On the basis of spectral investigations and quantum-chemical calculations, the scheme of interaction between system components that leads to formation of cyclic structures is developed.     

Synthesis of azo derivatives of 4-aminosalicylic acid

For searching a better 4-aminosalicylic acid derivative with higher activity and less side effects against the inflammatory bowel disease, 4-aminosalicylic acid (4-ASA) was protected by benzyloxycarbonyl and acetyl, respectively. The resultant was hydrogenized to remove protective group of amino group, then the product was reacted with NaNO2 to give diazonium salt, which was conjugated with salicylic acid, hydroxybenzene, TV-salicyloyl glycine acid to get azo derivatives of 4-ASA. The azo derivatives were hydrolyzed under the alkaline condition to get the target products. All compounds were characterized by FT-IR, 1H NMR, 13C NMR spectra in details. New derivatives of 4-ASA were characterized. The synthetic route was reasonable and feasible.     

系列Co-aip聚物的合成、结构及表面光电性能

采用水热法合成了3种以5-氨基间苯二甲酸根为桥连配体的Co(Ⅱ)配聚物:[Co2(aip)2(bipy)]n·2nH2O(1),[Co(aip)(imH)]n(2)和[Co(aip)(phen)]n(3)(H2aip=5-氨基间苯二甲酸,bipy=2,2′-联吡啶,imH=咪唑,phen=1,10-邻菲啰啉).通过X射...     

Determination of 5-aminosalicylic acid related impurities by micellar electrokinetic chromatography with an ion-pair reagent

A micellar electrokinetic chromatographic (MEKC) method was developed for the quantification of mesalazine or 5-aminosalicylic acid (5-ASA) and its major impurities 3-aminosalicylic acid, salicylic acid, sulfanilic acid and 4-aminophenol. The optimisation of the experimental conditions was carried out considering some important requirements: resolution, reproducibility, detection limits of 0.1% (m/m) or less, short total analysis time. Preliminary investigations employing sodium dodecyl sulfate (SDS) as surfactant did not lead to the necessary resolution of the studied compounds; the addition of tetrabutylammonium bromide (TBAB) to the SDS micellar system resulted in the complete separation of all the compounds. The effects on the separation by several parameters such as TBAB concentration, SDS concentration, background electrolyte pH and concentration, were evaluated. Using a fused-silica capillary (8.5 cm effective length) complete analysis was obtained in a very short time. Under the optimised final conditions [120 mM 3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid buffer, pH 10.20, 65 mM SDS in the presence of 55 mM TBAB and 5% methanol] the method was validated for specificity, precision, linearity, limits of detection and quantitation, and robustness: the 5-ASA related impurities can be quantified at least at the 0.1% (m/m) level.     

Synthesis,characterization, and antimicrobial activities of palladium Schiff base complexes derived from aminosalicylic acids

Six Schiff base compounds have been prepared from the condensation of o-vanillin, 2,3-dihydroxybenzaldehyde and 2,3,4-trihydroxybenzaldehyde with 4-aminosalicylic acid and 5-aminosalicylic acid (5-ASA). Addition of these Schiff bases to [Pd(OAc)₂] afforded the corresponding bis(salicylaldiminato)palladium(II) complexes in moderate to excellent yields. All new palladium complexes have been characterized fully using standard spectroscopic methods, elemental analyses and a single-crystal X-ray diffraction study in the case of 2e, the palladium complex containing Schiff base ligands derived from 5-ASA and 2,3-dihydroxybenzaldehyde. All derivatives of 5-ASA were examined for potential antimicrobial activities against two species of fungi, Aspergillus niger and Saccharomyces cerevisiae, as well as two species of bacteria, Bacillus cereus (Gram-positive) and Pseudomonas aeruginosa (Gram-negative).     

Synthesis and Antibacterial Evaluation of Cu(II), Co(II), and Mn(II) Complexes with Schiff Bases Derived from 5-Aminosalicylic Acid and o-Vanillin

Russian Journal of General Chemistry - The current study is devoted to the synthesis of Schiff base ligand, HL, by condensation of 5-aminosalicylic acid with o-vanillin, followed by preparing its...