Determination of pharmaceutical compounds in sewage sludge using a standard addition method approach

An analytical method for the simultaneous determination of eight pharmaceutical compounds in biosolids from urban wastewater treatment plants (WWTPs) was developed and validated. The compounds evaluated were non-steroidal anti-inflammatory drugs (naproxen, diclofenac, and ibuprofen), lipid regulators (clofibric acid), and antibiotics (sulfathiazole, sulfapyridine, sulfamethazine, and sulfamethoxazole). Ultrasound assisted extraction with a water–methanol solvent mixture (1:1, v:v) was performed and the compounds were then determined by liquid chromatography coupled with tandem mass spectrometry. The design of the method was based on the application of the standard addition calibration methodology to reduce matrix interferences. Validation procedures were conducted with rabbit excrements as blank samples. Recoveries of the target analytes ranged from 76 to 131% in spiked samples at 50, 200 or 1000 ng g^?1 dry weight (dw). The relative standard deviations were in the range of 5–15% and the method detection limits ranged from 2 to 12 ng g^?1dw. The method was applied to monitor pharmaceutical concentrations in biosolids from different WWTPs over an eight-month period (May to December 2011). Diclofenac, sulfapyridine and ibuprofen were detected in most of the samples whereas sulfamethazine and ibuprofen were the pharmaceuticals found in the highest concentrations (>200 ng g^?1 dw on average).     

CHOLESTERYL PHOSPHITE AND RELATED COMPOUNDS

Abstract

The preparation of cholesteryl phosphorodichloridite (2) is described; this compound with aniline (2 mol. equiv.) gave the N-phenylphosphoramidochloridite (5) and the latter by condensation with water afforded the N-phenyl-amidophosphite (6).

Similarly the N-phenylphosphoramidochloridite (5) with morpholine gave the morpholidite (7); phenylhydrazine gave the hydrazinophosphite (8) and ethanol the amidoethyl phosphite (9). Cholesteryl phosphorodichloridite (2) by reaction with aniline (4 mol. equiv.) gave the N,N ¹?diphenylphosphorodiamidite (10).

The reaction of cholesteryl phosphorodichloridite (2) with methanol and ethanol are discussed in relation to the analogous reactions with cholesteryl phosphorodichloridate. Boiling ethanol gave cholesterol as the only isolatable product but at room temperature a low yield of the diethylphosphite (11; R=Et) was obtained. The yield of the phosphite was greatly increased in the presence of base. Similarly the dichloridite 2 with boiling water gave cholesterol (1), but at room temperature cholesteryl phosphite 3 was isolated: the mechanistic basis for these different results is briefly discussed.

trans-4-t-Butylcyclohexanol with phosphorus trichloride gave the phosphorodichloridite, which was characterised by conversion to the corresponding N,N ¹?diphenylphosphorodiamidite.     

A 13C, 15N and 77Se NMR Study of Some Diseleno Sulfonamides

¹³C, ¹⁵N and ⁷⁷Se NMR data are reported for ten title compounds. Some linear correlations of selenium, nitrogen and carbon chemical shifts values are described. A number of one- and two- bond ⁷⁷Se-¹³C coupling constants values are also given.     

New Biologically Active N-(Tetrahydrobenzothienopyrimidin-4-YL)-Amino Acids,Thiourethane, Sulfonamides and Related Compounds

Abstract

Some derivatives of thieno[2,3-d]pyrimidine containing amino acids 3a-i, imidazoles 4a-f, isothiocyanate 5, thiourethane 6, triazine 8, pyrimidine 10, sulphonamides 13a-d, 14, pyrazole 16 and pyrazolone 17 were synthesized. The structural assignments of the new compounds were based on analytical, spectroscopic measurements and chemical reactions. Some of the obtained compounds showed interesting antimicrobial activities.     

Water‐Promoted Ring‐Opening Reactions of N‐Substituted Saccharins and Phthalimides by Amines

The reactions of N‐substituted saccharins and phthalimides with amines were promoted by water. Various o‐sulfamoyl benzamides and N,N′‐disubstituted phthalamides were prepared in moderate to good yields. These reactions have prominent advantages, such as short reaction time, less by‐products and simple isolation of the products. Water can probably stabilize the reaction intermediates and facilitate precipitation of the ring‐opening products. When steric hindrance arose, hydrolytic compounds, either free acid or salts of the acids, were obtained. Possible reason for the formation of amine salts of o‐sulfamoyl benzoic acids was proposed.     

Convenient One‐Pot Synthesis of Sulfonamides from Thiols using Trichloroisocyanuric Acid

A convenient synthesis of sulfonamides from thiols is described. In situ preparation of sulfonyl chlorides from thiols is accomplished by oxidation with trichloroisocyanuric acid (TCCA), benzyltrimethylammonium chloride and water (2.5 equiv). The sulfonyl chlorides are then further allowed to react with excess amine in the same reaction vessel. Triethylamine can be optionally added as acid scavenger.     

Cu(II)-catalyzed decarboxylation/elimination of N-arylsulfonyl amino acids to primary aryl sulfonamides

A novel protocol for CuO-catalyzed decarboxylation/elimination of N-arylsulfonyl amino acids was developed. It is the first example of using an accessible amino acid as an ammonia synthetic equivalent for the synthesis of primary aryl sulfonamides via oxidative decarboxylation/elimination reactions. The present protocol shows excellent functional group tolerance and provides an efficient method for the synthesis of primary aryl sulfonamides in excellent yields.     

Switching the Inhibitor-Enzyme Recognition Profile via Chimeric Carbonic Anhydrase XII

A key part of the optimization of small molecules in pharmaceutical inhibitor development is to vary the molecular design to enhance complementarity of chemical features of the compound with the positioning of amino acids in the active site of a target enzyme. Typically this involves iterations of synthesis, to modify the compound, and biophysical assay, to assess the outcomes. Selective targeting of the anti-cancer carbonic anhydrase isoform XII (CA XII), this process is challenging because the overall fold is very similar across the twelve CA isoforms. To enhance drug development for CA XII we used a reverse engineering approach where mutation of the key six amino acids in the active site of human CA XII into the CA II isoform was performed to provide a protein chimera (chCA XII) which is amenable to structure-based compound optimization. Through determination of structural detail and affinity measurement of the interaction with over 60 compounds we observed that the compounds that bound CA XII more strongly than CA II, switched their preference and bound more strongly to the engineered chimera, chCA XII, based on CA II, but containing the 6 key amino acids from CA XII, behaved as CA XII in its compound recognition profile. The structures of the compounds in the chimeric active site also resembled those determined for complexes with CA XII, hence validating this protein engineering approach in the development of new inhibitors.     

多壁碳纳米管固相萃取净化-高效液相色谱法测定猪肉和鸡肉中的磺胺多残留

建立了多壁碳纳米管为吸附剂的固相萃取净化-高效液相色谱-紫外检测测定猪肉和鸡肉中多种磺胺类药物多残留的方法。样品采用乙腈提取,多壁碳纳米管固相萃取净化,NaH₂PO₄缓冲溶液（pH 5.5~6.0）溶解上样,5%（v/v）丙酮-正己烷淋洗,丙酮-二氯甲烷（1：1,v/v）洗脱。色谱分离以50 mmol/L NaH₂PO₄-乙腈（7：3,v/v）为流动相,方法的线性范围为0.01~1.00 mg/L,线性相关系数大于0.998,检出限（LOD）为0.003 mg/L,定量限（LOQ）为0.01 mg/L。在0.02~0.2 mg/kg添加范围内,9种磺胺类药物的回收率高于70%,RSD低于8%,表明多壁碳纳米管对磺胺类药物具有较强的吸附富集能力。该方法简便、准确可用于动物组织及产品中磺胺药物残留的检测。     

超高效液相色谱-串联质谱法同时测定鸡肉中的二氯二甲吡啶酚、磺胺类和喹诺酮类药物残留

采用超高效液相色谱-串联质谱（UPLC-MS/MS）在正离子模式下通过多反应监测（MRM）方式同时测定了鸡肉组织中二氯二甲吡啶酚、磺胺嘧啶、磺胺二甲基嘧啶、磺胺对甲氧嘧啶、磺胺甲氧哒嗪、诺氟沙星、氧氟沙星、环丙沙星、恩诺沙星等9种药物残留。试样经乙腈均质提取,冷冻离心脱脂,旋转蒸发浓缩,用流动相复溶后经乙腈饱和的正己烷除油,随后进行UPLC-MS/MS定性定量分析。该方法测定9种药物的检出限为0.1 μg/kg,定量限为0.5 μg/kg。在添加水平分别为0.5、1.0和2.0 μg/kg时,9种药物的加标回收率为81.5%~97.6%,相对标准偏差（RSD）为2.1%~8.9%。该方法简便、准确,可作为鸡肉中9种药物残留检测的确证方法。