Simultaneous determination of sulfaquinoxaline, sulfamethazine and pyrimethamine by liquid chromatography

A liquid chromatography method is described to determine sulfaquinoxaline (SQX), sulfamethazine (SMT), and pyrimethamine (PMT), by using a Kromasil C₁₈ column and a 40 mM NaH₂PO₄ buffer solution, containing 10 mM NaClO₄ (pH 3.0)–acetonitrile (65:35) as mobile phase. The mobile phase flow-rate and sample volume injected were 1.5 ml/min and 20 μl, respectively and the samples were dissolved in the mobile phase. The limits of quantification were found to be about 180 μg/l (3.6 ng) for each compound. The method was applied in veterinary commercial formulations. Analyses were made by means of the standard addition method, whose results were compared with those obtained by preparing “tests” (from the stock solutions) and with those obtained by a capillary electrophoresis method. Both methods showed similar results, and then it was proved that some commercial claimed levels were not in agreement with the obtained results by using our analytical method, as they were in other cases.     

Hydrogen bonding patterns in bis(pyrimethamine hydrogen sulfate) monohydrate

The crystal structure of the compound bis [2,4-diamino-5-(p-chlorophenyl)-6-ethyl pyrimidinium hydrogen sulfate] monohydrate was studied by X-ray diffraction methods. The compound crystallises in orthorhombic system, space group P2₁2₁2₁, a=18.531(2) ?, b=16.190(2) ?, c=10.777(2) ?, V=3233.3(8), Z=4. The asymmetric unit shows the presence of two crystallographically independent pyrimethamine molecules, two hydrogen sulfate anions, and a water molecule. The hydrogen sulfate anions form a cyclic hydrogen bonded motif R₂ ²(8) with the 2-amino pyrimidine of the respective protonated pyrimethamine cations, through N–H···O hydrogen bonds. Thus the sulfate anions mimic the role of carboxylate anions observed in many aminopyrimidine-carboxylate interactions. This motif self assembles through DDAA array of quadruple hydrogen bonds, N–H···Cl, O–H···O and C–H···O hydrogen bonds.Supplementary material CCDC-293607 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre (CCDC), 12 Union Road, Cambridge CB2 IEZ, UK; fax: C44 (0) 1223-336033; e-mail: deposit@ccdc.cam.ac.uk].     

液相色谱-线性离子阱-静电场轨道阱回旋共振组合质谱法鉴定乙胺嘧啶在大鼠体内的代谢物

研究乙胺嘧啶在大鼠体内的代谢方式与途径.大鼠以5 mg/kg单剂量口服乙胺嘧啶后,在不同时间点分别采集其血液、尿液和粪便样品.采用液相色谱-线性离子阱-静电场轨道阱回旋共振组合质谱仪(LC-LTQ-Orbitrap)检测乙胺嘧啶在大鼠体内的代谢物,结合相关代谢软件,共鉴定出10种代谢产物,主要的代谢途径包括苯环上的羟基化、N-氧化、双氧化、Ⅳ-葡萄糖醛酸结合、甲基化+葡萄糖醛酸结合、羟基化+葡萄糖醛酸结合和Ⅳ-氧化+葡萄糖醛酸结合.除乙胺嘧啶3-N-氧化物已经在大鼠体外代谢研究中被发现外,其余9种代谢产物均首次在大鼠体内发现.根据其精确分子量及多级质谱的碎片特征,对这些代谢产物的化学结构做出推断,并建立乙胺嘧啶在大鼠体内的代谢谱系.研究表明,乙胺嘧啶在大鼠体内的Ⅰ相代谢方式主要是羟基化和N位氧化,Ⅱ相代谢方式主要是甲基化和葡萄糖醛酸结合.     

Interaction of pyrimethamine and sulfadiazine with ionic and neutral micelles: Electronic absorption and fluorescence studies

The binding of two antitoxoplasmosis drugs, pyrimethamine (PYR) and sulfadiazine (SDZ) to cationic cetyltrimethylammonium chloride (CTAC), anionic sodium dodecylsulfate (SDS), zwiterionic N-hexadecyl-N,N-dimethyl-2-ammonium-1-propanesulfonate (HPS) and neutral polyoxyethylene-dodecyl-ether (Brij-35^®) micelles was studied using absorption and fluorescence spectroscopic methods. The pK_a of PYR changed in the presence of charged anionic, cationic and zwiterionic micelles, indicating that interaction is influenced by the micellar charge. For SDZ, pK_a changes were lower than 1 for all micelles, suggesting the occurrence of low binding constants in addition to a reasonable influence of the micellar charge. The values of binding constants K_b, obtained from fluorescence measurements, for PYR to CTAC micelles were very low at pH 4.0, where the drug is in a complete protonated state, increasing at pH 9.0 to long-chained CTAC and HPS micelles since this factor also favors accomodation of the neutral drug in the hydrophobic compartments. For SDZ the binding constants were determined from optical absorption measurements. Low binding constants were observed to charged surfactant micelles, with influence of micellar charge. It must be stated however that those values can be underestimated due to the relatively low sensitivity of the method based on absorption measurements.