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Related Substances (relate + substance)
Selected AbstractsThe Synthesis and Biological Activity of Pyranonaphthoquinone Derivatives from Streptomyces sp. and Their Related Substances.CHEMINFORM, Issue 8 2005Akiko Shimbashi Abstract For Abstract see ChemInform Abstract in Full Text. [source] Determination of the chiral and achiral related substances of methotrexate by cyclodextrin-modified micellar electrokinetic chromatographyELECTROPHORESIS, Issue 16 2004Roberto Gotti Abstract A cyclodextrin-modified micellar electrokinetic chromatographic (CD-MEKC) method for the determination of the most important potential impurities of methotrexate (MTX): 2,4-diamino-6-(hydroxymethyl)pteridine, aminopterine hydrate, 4-[N -(2-amino-4-hydroxy-6-pteridinylmethyl)- N -methylamino] benzoic acid, 4-[N -(2,4-diamino-6-pteridinylmethyl)- N -methylamino] benzoic acid, and the distomer D -MTX is presented. The MEKC separation of these compounds was optimized by applying a step-by-step approach. The addition of ,-CD to a conventional MEKC system, based on sodium dodecyl sulfate (SDS) as surfactant, showed to be essential for the enantioresolution of racemic MTX as well as for the separation of the achiral impurities. To achieve high-resolution factor between the peaks adjacent to the main component (L -MTX), as required in the analysis of related impurities, the separation conditions were stressed; in particular, the addition of methanol to the CD-MEKC system resulted in a very effective choice. Under the optimized final conditions (100 mM SDS and 45 mM ,-CD in a mixture of 50 mM borate buffer, pH 9.30-methanol (75:25 v/v)), the method was validated showing a general adequate accuracy (93,106% recovery) in the determination of L -MTX related substances at the impurity level of 0.12% w/w with a relative standard deviation (RSD)% lower than 8% (n = 4). The method was successfully applied to the analysis of pharmaceuticals (tablets and injections) which showed to contain the distomer D -MTX as major impurity and aminopterine hydrate as a further related substance in the commercial tablets. [source] The role of NAAG and NAALADase in axon-to-glia signallingJOURNAL OF NEUROCHEMISTRY, Issue 2002R. M. Grossfeld Recent investigations from our laboratories have identified N-acetylaspartylglutamate (NAAG) as the probable primary axon-to-glia signalling agent and source of signalling glutamate (GLU) at nonsynaptic regions of crayfish nerve fibers. NAAG is released from giant axons and mimics the action of the natural signalling agent in hyperpolarizing the glia. GLU formed extracellularly during inactivation of NAAG by NAALADase has a similar, but smaller, effect on the glia. A consequence of these actions of NAAG and GLU appears to be an activation of a signal transduction cascade leading to modulation of water and K+ homeostasis of the neuronal microenvironment. GLU or a related substance also appears to be a neuron-glia signalling agent at nonsynaptic and synaptic regions of vertebrate nervous system. Therefore, conserved mechanisms of neuron-glia signalling, mediated at least in part by NAAG and/or GLU, may regulate signal transmission and processing at axons and synapses under physiological and pathological conditions in invertebrates and vertebrates. Acknowledgements: ,Supported by NIH grant NS34799 and Guilford Pharmaceuticals (Baltimore, MD). [source] Reactivity of in vitro activated human T lymphocytes to p -phenylenediamine and related substancesCONTACT DERMATITIS, Issue 4 2008Claudia Skazik Background:, Patch tests to p -phenylenediamine (PPD) and related substances often show concurrent reactions that can be attributed to separate sensitization or cross-reactivity. Objectives:, In order to understand the health risks associated with cross-reactivity, we studied cross-reactivity of eight chemicals in vitro by measurement of T-cell proliferation of peripheral blood mononuclear cells (PBMC), T-cell lines (TCL), and T-cell clones (TCC) of subjects with a positive patch test result to PPD. Patients/Methods:, We studied PBMC from 13 patients and were able to generate TCL from seven and TCC from four patients. Their proliferative responses to the chemicals were estimated. Results:, Concurrent reactions to these compounds on the polyclonal and monoclonal level were found. A restricted T-cell receptor (TCR) V,16-usage was observed (5/8 clones). A detailed analysis of 34 TCL showed broad cross-reactivity (64.7%) between PPD, p -toluenediamine, Bandrowski's Base, and p -aminoazobenzene. More restricted patterns were found in 8.8%, which responded only to compounds with two or three benzene rings, whereas 26.5% of the clones reacted specifically only to one compound. Conclusion:, More than 60% of the clones showed a broad cross-reactivity pattern. Hence, clinically observed cross-reactivity between different para-amino compounds can be based on a TCR recognizing similar epitopes of these compounds with low specificity. [source] CE assay for simultaneous determination of charged and neutral impurities in dexamphetamine sulfate using a dual CD systemELECTROPHORESIS, Issue 9 2010Sudaporn Wongwan Abstract A CE assay for the simultaneous determination of charged and uncharged potential impurities (1S,2S -(+)-norpseudoephedrine, 1R,2S -(,)-norephedrine, phenylacetone and phenylacetone oxime) of dexamphetamine sulfate including the stereoisomer levoamphetamine was developed and validated. The optimized background electrolyte consisted of a 50,mM sodium phosphate buffer, pH 3.0, containing 80,mg/mL sulfobutylether-,-CD and 25,mg/mL sulfated ,-CD. Separations were performed in 40.2/35,cm, 50 ,m id fused-silica capillaries at a temperature of 20°C and an applied voltage of ,10,kV. 1R,2S -(,)-ephedrine was used as internal standard. The assay was validated in the range of 0.05,1.0% for the related substances and in the range of 0.05,5.0% for levoamphetamine. The LOD was 0.01,0.02% depending on the analyte. The assay also allowed the separation of the E,Z-stereoisomers of phenylacetone oxime. The effect of the degree of substitution of sulfobutylether-,-CD was investigated. In commercial samples of dexamphetamine sulfate between 3.2 and 3.7% of levoamphetamine were found. Furthermore, phenylacetone and phenylacetone oxime could be observed at the LOD, indicating the synthetic origin of the investigated samples. [source] Determination of the chiral and achiral related substances of methotrexate by cyclodextrin-modified micellar electrokinetic chromatographyELECTROPHORESIS, Issue 16 2004Roberto Gotti Abstract A cyclodextrin-modified micellar electrokinetic chromatographic (CD-MEKC) method for the determination of the most important potential impurities of methotrexate (MTX): 2,4-diamino-6-(hydroxymethyl)pteridine, aminopterine hydrate, 4-[N -(2-amino-4-hydroxy-6-pteridinylmethyl)- N -methylamino] benzoic acid, 4-[N -(2,4-diamino-6-pteridinylmethyl)- N -methylamino] benzoic acid, and the distomer D -MTX is presented. The MEKC separation of these compounds was optimized by applying a step-by-step approach. The addition of ,-CD to a conventional MEKC system, based on sodium dodecyl sulfate (SDS) as surfactant, showed to be essential for the enantioresolution of racemic MTX as well as for the separation of the achiral impurities. To achieve high-resolution factor between the peaks adjacent to the main component (L -MTX), as required in the analysis of related impurities, the separation conditions were stressed; in particular, the addition of methanol to the CD-MEKC system resulted in a very effective choice. Under the optimized final conditions (100 mM SDS and 45 mM ,-CD in a mixture of 50 mM borate buffer, pH 9.30-methanol (75:25 v/v)), the method was validated showing a general adequate accuracy (93,106% recovery) in the determination of L -MTX related substances at the impurity level of 0.12% w/w with a relative standard deviation (RSD)% lower than 8% (n = 4). The method was successfully applied to the analysis of pharmaceuticals (tablets and injections) which showed to contain the distomer D -MTX as major impurity and aminopterine hydrate as a further related substance in the commercial tablets. [source] Determination and fate of oxytetracycline and related compounds in oxytetracycline production wastewater and the receiving river,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2008Dong Li Abstract This study investigated the occurrence and fate of oxytetracycline (OTC) and its related substances, 4-epi-oxytetracycline (EOTC), ,-apo-oxytetracycline (,-apo-OTC), and ,-apo-oxytetracycline (,-apo-OTC), in a wastewater treatment plant (WWTP) treating OTC production wastewater and a river receiving the effluent from the WWTP using liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). The percent removal of OTC in the WWTP was 38.0 ± 10.5%, and the concentration of OTC was still up to 19.5 ± 2.9 mg/L in the treated outflow. The concentration slightly decreased along the river, from 641 ± 118 ,g/L at site R2 (discharging point) to 377 ± 142 ,g/L at site R4 (,20 km from site R2), which was still higher than the minimal inhibition concentration of OTC reported (,250 ,g/L). On the other hand, the total amount of its related substances in the treated effluent was less than 5% of OTC. Concentrations of ,-apo-OTC and ,-apo-OTC increased along the river, from 5.76 ± 0.63 and 2.08 ± 0.30 ,g/L at site R2 to 11.9 ± 4.9 and 12.0 ± 4.6 ,g/L at R4, respectively, although EOTC decreased from 31.5 ± 3.8 to 12.9 ± 1.1 ,g/L, respectively. The mean concentration of ,-apo-OTC in river sediments was 20.8 ± 7.8 mg/kg, and its ratio to OTC was approximately 0.11, nearly twice the ratio of ,-apo-OTC and EOTC to OTC (0.058 ± 0.014 and 0.061 ± 0.015, respectively). [source] Electron ionization mass spectrometric study of monomeric models of O -polysaccharides of Vibrio cholerae O:1, serotypes Ogawa and InabaJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 9 2003Vladimír Ková Abstract Fragmentation mechanisms of electron ionization (EI) mass spectrometry of the title compounds have been elucidated by high-resolution (HR) mass spectrometric measurements of the elemental composition and measurements of the metastable transitions (B2/E, CID). The experimental results were interpreted with the help of Mass Frontier 3.0 software, which aided the elucidation of fragmentation mechanisms and helped to deduce structures of the ions formed. Characteristic under the conditions of EI-MS measurement was the production of protonated adducts. Three distinct pathways observed include the formation of oxonium type ions, the conjugated transfer of electrons in the pyranose ring, and cleavage of the acylamide side chains. By applying the results obtained, the molecular mass, as well as the structures of both the saccharide and acylamide side chain involved in related substances, can be determined. Copyright © 2003 John Wiley & Sons, Ltd. [source] Enantioselective HPLC resolution of synthetic intermediates of armodafinil and related substancesJOURNAL OF SEPARATION SCIENCE, JSS, Issue 6-7 2008Ramisetti Nageswara Rao Abstract Armodafinil is a unique psychostimulant recently approved by the US Food and Drug Administration for the treatment of narcolepsy. The chromatographic resolution of its chiral intermediates including related substances in the total synthesis of armodafinil was studied on polysaccharide-based stationary phases, viz. cellulose tris-(3,5-dimethylphenylcarbamate) (Chiralcel OD-H) and amylose tris-(3,5-dimethylphenylcarbamate) (Chiralpak AD-H) by HPLC. The effects of 1-propanol, 2-propanol, ethanol, and trifluoroacetic acid added to the mobile phase and of column temperature on resolution were studied. A good separation was achieved on cellulose-based Chiralcel OD-H column compared to amylose-based Chiralpak AD-H. The effects of structural features of the solutes and solvents on discrimination between the enantiomers were examined. Baseline separation with Rs >1.38 was obtained using a mobile phase containing n -hexane,ethanol,TFA (75:25:0.15 v/v/v). Detection was carried out at 225 nm with photodiode array detector while identification of enantiomers was accomplished by a polarimetric detector connected in series. The method was found to be suitable not only for process development of armodafinil but also for determination of the enantiomeric purity of bulk drugs and pharmaceuticals. [source] Development and validation of a reverse-phase liquid chromatographic method for assay and related substances of abacavir sulfateJOURNAL OF SEPARATION SCIENCE, JSS, Issue 1 2007U. Seshachalam Abstract A simple isocratic liquid chromatographic method was developed for the determination of abacavir from its related substances and assay for the first time. This method involves the usage of C18 (Intertsil octadecyl silane-3V, 150 mm×4.6 mm, 5 ,m) column. The method was validated over the range of 0.002,0.1 mg/mL for chloro impurity, 0.005,0.1 mg/mL for amino impurity and pyrimidine impurity, and 0.005,0.2 mg/mL for abacavir. The mobile phase consists of a mixture of 10 mM ammonium acetate buffer and ACN in the ratio of 90 : 10. The flow rate was set at 1.0 mL/min with UV detection monitored at 214 nm. The drug substance was subjected to stress conditions of hydrolysis, oxidation, photolysis, and thermal degradation. The developed method was validated for linearity, range, precision, accuracy, and specificity. This method can be conveniently used in a quality control laboratory for routine analysis of both related substances and assay. [source] Determination of the purity of ampicillin by micellar electrokinetic chromatography and reversed phase liquid chromatography on a monolithic silica columnJOURNAL OF SEPARATION SCIENCE, JSS, Issue 7-8 2004Milada Dole, alová Abstract A micellar electrokinetic chromatographic (MEKC) method and a fast reversed-phase liquid chromatographic one have been developed for determining the purity of ampicillin. MEKC separation of ampicillin and its related substances was performed with the use of an untreated fused-silica capillary and 40 mM phosphate-borate buffer, pH 7.5 containing 75 mM SDS. The HPLC method employed a monolithic silica C18 column and a mobile phase composed of phosphate buffer, pH 5.2 and ACN, the flow rate being 4.0 mL/min. Both methods were successfully validated. Linearity, relative response factors, limits of quantitation, intermediate precision, and accuracy were evaluated. The methods proved to be fast, reliable, and sufficiently sensitive and, accordingly, well-suited for control of purity of ampicillin substance, injections, and capsules. A combination of both methods can be very useful in the confirmation of impurity profiles. [source] Influence of substituent groups at the 3-position on the mass spectral fragmentation pathways of cephalosporinsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 14 2010Jin Li The structural fragment ions of nine cephalosporins were studied by electrospray ionization quadrapole trap mass spectrometry (Q-Trap MSn) in positive mode. The influence of substituent groups in the 3-position on fragmentation pathway B, an ,-cleavage between the C7C8 single bond, coupled with a [2,4]-trans-Diels-Alder cleavage simultaneously within the six-membered heterocyclic ring, was also investigated. It was found that when the substituent groups were methyl, chloride, vinyl, or propenyl, fragmentations belonging to pathway B were detected; however, when the substituents were heteroatoms such as O, N, or S, pathway B fragmentation was not detected. This suggested that the [M,R3]+ ion, which was produced by the bond cleavage within the substituent group at the 3-position, had a key influence on fragmentation pathway B. This could be attributed to the strong electronegativity of the heteroatoms (O, N, S) that favors the production of the [M,R3]+ ion. Moreover, having the positive charge of the [M,R3]+ ion localized on the nitrogen atom in the 1-position changed the electron density distribution of the heterocyclic structure, which prohibits a [2,4]-reverse-Diels-Alder fragmentation and as a result fragmentation pathway B could not occur. The influence of the substituent group in the 3-position was determined by the intensity ratio (e/d) of ions produced by fragmentation pathway A, a [2,2]-trans-Diels-Alder cleavage within the quaternary lactam ring, including the breaking of the amide bond and the C6C7 single bond (ion d), and fragmentation pathway B (ion e). The results indicate that the electronegativity of the substituent group was a key influencing factor of pathway B fragmentation intensity, because the intensity ratio (e/d) is higher for a chlorine atom, a vinyl, or a propenyl group than that of a methyl group. This study provided some theoretical basis for the identification of cephalosporin antibiotics and structural analysis of related substances in drugs. Copyright © 2010 John Wiley & Sons, Ltd. [source] Properties of fucoidan from Cladosiphon okamuranus tokida in gastric mucosal protectionBIOFACTORS, Issue 4 2000Hideyuki Shibata Abstract To elucidate the anti-ulcer potential of Cladosiphon fucoidan, anti-peptic activity, bFGF stabilizing activity and inflammatory properties of this and related substances were investigated. Anti-peptic activity was observed with this and other sulfated polysaccharides such as dextran sulfate, carrageenan, and Fucus fucoidan. However, non-sulfated polysaccharides such as mannan and dextran did not exert the anti-peptic activity. The loss of bFGF bioactivity was prevented by all sulfated polysaccharides tested except chondroitin sulfate, at pH 7.4 and at pH 4.0. At pH 2.0, only heparin protected the bFGF activity. The generation of superoxide by macrophages and PMNs was stimulated by dextran sulfate, carrageenan, and Fucus fucoidan, whereas Cladosiphon fucoidan, heparin and chondroitin did not. Dextran sulfate, carrageenan, and Fucus fucoidan also stimulated the secretion of TNF, from macrophages, while Cladosiphon fucoidan did not. Thus, Cladosiphon fucoidan is a sulfated polysaccharide without inflammatory action. These results suggest that Cladosiphon fucoidan is a safe substance with potential for gastric protection. [source] | |||||||||||||