The binding of orally dosed hydrophobic active pharmaceutical ingredients to casein micelles in milk

Casein proteins (α_S1-, α_S2-, β- and κ-casein) account for 80% of the total protein content in bovine milk and form casein micelles (average diameter = 130 nm, approximately 10¹⁵ micelles/mL). The affinity of native casein micelles with the 3 hydrophobic active pharmaceutical ingredients (API), meloxicam [351.4 g/mol; log P = 3.43; acid dissociation constant (pK_a) = 4.08], flunixin (296.2 g/mol; log P = 4.1; pK_a = 5.82), and thiabendazole (201.2 g/mol; log P = 2.92; pK_a = 4.64), was evaluated in bovine milk collected from dosed Holstein cows. Native casein micelles were separated from raw bovine milk by mild techniques such as ultracentrifugation, diafiltration, isoelectric point precipitation (pH 4.6), and size exclusion chromatography. Acetonitrile extraction of hydrophobic API was then done, followed by quantification using HPLC-UV. For the API or metabolites meloxicam, 5-hyroxy flunixin and 5-hydroxy thiabendazole, 31 ± 3.90, 31 ± 1.3, and 28 ± 0.5% of the content in milk was associated with casein micelles, respectively. Less than ～5.0% of the recovered hydrophobic API were found in the milk fat fraction, and the remaining ～65% were associated with the whey/serum fraction. A separate in vitro study showed that 66 ± 6.4% of meloxicam, 29 ± 0.58% of flunixin, 34 ± 0.21% of the metabolite 5-hyroxy flunixin, 50 ± 4.5% of thiabendazole, and 33 ± 3.8% of metabolite 5-hydroxy thiabendazole was found partitioned into casein micelles. Our study supports the hypothesis that casein micelles are native carriers for hydrophobic compounds in bovine milk.     

噻菌灵的合成工艺研究

噻菌灵是一种高效、广谱性杀菌剂,在农业领域有广泛应用。介绍了改进的噻菌灵合成工艺,以2-(1-羟乙基)苯并咪唑为原料,在磷钨杂多酸存在下用H_2O_2催化氧化得到2-乙酰基苯并咪唑,再经溴素卤化得到1-(1H-苯并咪唑-2-基)-2-溴乙酮,最后与硫代甲酰胺合环得到2-(4-噻唑基)-1H-苯并咪唑,即目标化合物,总收率为67.9%,HPLC纯度为98.1%。其化学结构经~1HNMR分析得到确证。     

高效液相色谱法测定竹筷中噻苯咪唑、邻苯基苯酚和联苯

建立高效液相色谱测定竹筷中噻苯咪唑、邻苯基苯酚、联苯的方法。以甲醇为提取溶剂,用索氏提取法提取竹筷中噻苯咪唑、邻苯基苯酚和联苯3种保鲜剂。以甲醇-水(体积比70:30)为流动相,流速1.0mL/min,采用C18柱(250mm×4.6mm,5μm)分离,紫外检测器检测,检测波长247nm,进样量20μL。方法的相关系数均大于0.999,最低检出限为0.01μg/mL,平均回收率为95.8%～97.1%,相对标准偏差为1.4%～2.6%。应用所建立的方法测定一次性竹筷中噻苯咪唑、邻苯基苯酚、联苯的残留量,结果表明：该方法样品处理简单,色谱分离完全,结果准确可靠,适于竹筷中噻苯咪唑、邻苯基苯酚和联苯的分析检测。     

Feasibility of LC/TOFMS and elemental database searching as a spectral library for pesticides in food

Traditionally, the screening of unknown pesticides in food has been accomplished by GC/MS methods using conventional library-searching routines. However, many of the new polar and thermally labile pesticides are more readily and easily analysed by LC/MS methods and no searchable libraries currently exist (with the exception of some user libraries, which are limited). Therefore, there is a need for LC/MS libraries that can detect pesticides and their degradation products. This paper reports an identification scheme using a combination of LC/MS time-of-flight (accurate mass) and an Access database of 350 pesticides that are amenable to positive ion electrospray. The approach differs from conventional library searching of fragment ions. The concept consists of three parts: (1) initial screening of possible pesticides in actual market-place fruit extracts (apple and orange) using accurate mass and generating an accurate mass via an automatic ion-extraction routine, (2) searching the Access database manually for screening identification of a pesticide, and (3) identification of the suspected compound by accurate mass of at least one fragment ion and comparison of retention time with an actual standard. Imazalil and iprodione were identified in apples and thiabendazole in oranges using this database approach.     

基于复合功能单体噻菌灵印迹传感器的制备及应用

目的：快速检测食品中噻菌灵残留量。方法：通过紫外光谱法筛选邻氨基苯酚和邻苯二胺作为复合功能单体,采用电化学分析法研究了聚合条件、洗脱条件,对传感器性能进行了评价,建立了食品中噻菌灵残留的快速检测方法。结果：在最佳条件下,该印迹传感器对噻菌灵及其结构类似物具有特异吸附性能,且对噻菌灵的选择性最强;该方法的线性范围在1×10^-8～1×10^-4 mol/L,检出限为3.3×10^-9 mol/L,样品加标平均回收率为88.16%～100.73%,相对标准偏差（RSD）≤2.63%。结论：该传感器具有优异的印迹效应以及良好的选择性、重现性与稳定性,可用于食品中噻菌灵残留的快速检测。     

快速分离柱高效液相色谱法测定环境水样中多菌灵和噻菌灵的研究

研究并建立了用固相微萃取-快速分离柱高效液相色谱法测定环境水样中的多菌灵和噻菌灵的方法。样品中的多菌灵和噻菌灵用W aters Sep-pak C18反相固相萃取小柱预分离和富集,然后以ZORBAX Stab leBound(4.6 mm×50 mm,1.8μm)C18快速分离柱为固定相,甲醇-水(V(甲醇)/V(水)=1∶1)为流动相进行分离,流速为2.0 mL/m in;用二极管矩阵检测器检测,检测波长为286 nm,样品中的多菌灵和噻菌灵在2.0 m in内可达到基线分离。方法标准回收率为93%~104%,RSD为2.1%~3.2%。用新方法测定了环境水样中的多菌灵和噻菌灵,结果令人满意。     

Structure, properties and application to water-soluble coatings of complex antimicrobial agent Ag-carboxymethyl chitosan-thiabendazole

The structure, properties and application to water-soluble coatings of a new complex antimicrobial agent Ag-carboxylmethyl citosan-thiabendazole （Ag-CMCTS-TBZ） prepared from different materiel ratios were reported. The silver ions were preferably coordinated with the free-NH2 groups and the -OH groups of secondary alcohol and carboxyl in CMCTS. TBZ preferably bonded to carboxyl group in CMCTS by electrostatic force and hydrogen bonding. Increase in silver ions content in the complex agent improved to some limited extent the antibacterial activity, but enhanced coloring and cost of the complex agent. Increase in TBZ content resulted in increase of antifungal activity, but decrease of water solubility of the complex agent. The antimicrobial MICs of the complex agent to Esherichia coil, Staphylococcus aureus, Candida albicans, Aspergillus niger, Mucor sp. were 20 -80, 15 -60, 20 - 55, 40 - 250, and 400 - 1700 mg/kg, respectively. Addition of 0.1% of this complex agent to acrylic emulsion paint made the paint without substantial change in color, luster, viscosity, odor or pH value, but with an excellent and chronically persisting broad-spectra antimicrobial activity.     

A sensitive determination method for carbendazim and thiabendazole in apples by solid-phase microextraction−high performance liquid chromatography with fluorescence detection

A new analytical method for the determination of carbendazim (MBC) and thiabendazole (TBZ) in apples is reported, based on solid-phase microextraction (SPME) coupling HPLC with fluorescence detection. The main SPME and HPLC experimental conditions were optimized. The apples were first blended and centrifuged. Then, an aliquot of the resulting solution was subjected to SPME on a 60 µm polydimethylsiloxane/divinylbenzene (PDMS/DVB) fibre for 35 min at room temperature with the solution being stirred at 1100 rev min^–1. The extracted pesticides on the SPME fibre were desorbed in the mobile phase into the SPME/HPLC interface for HPLC analysis. The method was linear over the range 0.01–1 mg kg^–1 in apples for both MBC and TBZ, with detection limits of 0.005 and 0.003 mg kg^–1 and correlation coefficients of 0.9995 and 0.9998, respectively. The average recoveries for MBC and TBZ were 91.5 and 92.3% with the relative standard deviations (RSD) of 4.7 and 4.1% at the 0.1 mg kg^–1 level, and 94.6 and 96.1% with RSD of 3.3 and 3.8% at the 0.5 mg kg^–1 level, respectively. The method is simple, sensitive, organic solvent-free and is suitable for the determination of MBC and TBZ in apples.     

多聚磷酸为助剂合成食品保鲜剂

介绍多聚磷酸作为 4 羧酸噻唑与邻苯二胺溶剂兼脱水剂 ,合成噻苯咪唑———食品保鲜剂的方法。指出多聚磷酸作为溶剂性能优于氯苯、邻二氯苯 ,并找到较好的反应条件 ,噻苯咪唑转化率达 90 .5%