恩诺沙星及代谢物在西伯利亚鲟疾病模型内的药动学及残留消除规律

采用高效液相色谱法,研究了20℃条件下人工感染嗜水气单胞菌的西伯利亚鲟口灌恩诺沙星(剂量10 mg/kg)后,其血液中药代动力学规律,采用药代动力学软件3p97对药物浓度时间数据进行分析。结果表明,恩诺沙星及代谢物环丙沙星在感染嗜水气单胞菌的西伯利亚鲟体内的药时量曲线关系符合二室模型,达峰时间T_(max)分别为0.37 h和1.12 h;峰浓度值C_(max)分别为0.329和0.164 mg/L;表观分布容积V_d分别为40.12和49.239 L/kg,吸收半衰期T(1/2)α分别为5.732和8.17 h;消除半衰期T(1/2)β分别为45.131和40.521 h。与健康西伯利亚鲟相比,恩诺沙星及代谢物在受感染的西伯利亚鲟体内,吸收相对缓慢,消除也慢。恩诺沙星在疾病模型西伯利亚鲟肝脏和肌肉中的消除方程分别为:C=0.13e~(-0.005t),C=2.31e~(-0.006t);R~2≥0.825;环丙沙星在疾病模型西伯利亚鲟肝脏和肌肉中的的消除方程分别为:C=4.412e~(-0.007t);C=4.915e~(-0.004t);R~2≥0.758。     

石榴皮总黄酮中山奈酚大鼠体内药动学研究

目的建立高效液相色谱法(HPLC)测定石榴皮总黄酮中山奈酚在大鼠体内的血药浓度,并探讨其在大鼠体内的药动学特征。方法 SD大鼠灌胃石榴皮总黄酮,不同时间点眼后静脉丛取血,预处理后测定血浆中山奈酚的浓度,3P97软件处理数据。结果石榴皮总黄酮中山奈酚在大鼠体内的药动学符合二房室模型,山奈酚在体内吸收较快,给药后1 h即达峰浓度(Cmax),为1.746±0.199 mg/L,吸收速率常数Ka=2.816±0.574h~(-1),分布速率常数α=1.312±0.288 h~(-1),消除速率常数β=0.128±0.072 h~(-1),消除半衰期t1/2β=10.124±6.853 h,药时曲线下面积AUC0-24=8.793±2.575 mg·h/L。结论 HPLC测定血浆中山奈酚浓度准确、简便,适用于石榴皮总黄酮中山奈酚的药动学研究。     

油菜花粉有效成分山奈酚在家兔体内的药代动力学研究

目的:采用高效液相色谱法研究健康家兔被灌胃油菜花粉(15 g/kg)后的山奈酚药代动力学.方法:对动物给药后,在不同时间分点经颈静脉采血,血浆样品的酶解物通过C18小柱富集,对甲醇洗提部分进行色谱分析.药代动力学参数运用PKS软件处理.结果:家兔被灌胃油菜花粉后山奈酚浓度-时间曲线符合一级吸收二室模型.主要药动学参数:AUC(1.4599±0.4389)(μg·h)/L、Tpeak(3.7143±0.9512)h、Cmax(0.2455±0.0615)μg/mL、T1/2β(1.99±0.19)h、Vd(31.418±8.010)L/kg.结论:家兔被灌胃油菜花粉后,山奈酚具有吸收较缓慢,体内分布广,消除迅速的特点.     

呋喃西林代谢物在凡纳滨对虾体内代谢及残留

为研究呋喃西林代谢物氨基脲(semicarbazide,SEM)在凡纳滨对虾体内代谢及残留消除.在试验水温(28±2)℃下,以30 mg/kg的剂量对凡纳滨对虾多次药饵给药后,采用高效液相色谱-串联质谱法测定血淋巴和组织中药物浓度,并通过WinNonlin 5.2药代动力学软件及Excel 2010软件进行数据分析.经房室模型分析,SEM在血淋巴中吸收、分布、消除半衰期(t1/2K01、t1/2α、t1/2β)分别为0.695,2.567,47.603 h.经非房室模型的统计矩原理分析,SEM在血淋巴、肌肉、鳃、肝胰腺和肠的平均驻留时间MRT分别为34.424,49.281,39.178,32.390,35.170 h.停药2d后药-时曲线经Excel拟合,SEM在血淋巴、肌肉、鳃、肝胰腺和肠的消除半衰期t1/2β大小为肌肉11.75 d＞血淋巴8.88 d＞鳃8.66 d＞肝胰腺5.37 d＞肠线4.71d.结果表明,SEM在凡纳滨对虾体内吸收快、分布广,但消除缓慢.     

邻苯二甲酸二（2-乙基己基）酯在青春期小鼠体内的代谢动力学研究

研究邻苯二甲酸二（2-乙基己基）酯（di-（2-ethylhexyl）phthalate,DEHP）在青春期小鼠体内的代谢动力学,以300 mg/kg DEHP灌胃青春期小鼠,血清样品经固相萃取（solid phase extraction,SPE）提取和净化,气相色谱-质谱联用（gas chromatography-mass spectrometry,GC-MS）法测定不同时间点的血药质量浓度,以3p97软件拟合其动力学参数。DEHP在青春期小鼠体内的主要药物代谢动力学参数：药峰质量浓度ρmax为（0.476±0.028） μg/mL,达峰时间Tpeak为（2.539±0.424） h,药-时曲线下面积AUC（0-t）为（32.209±11.220） h•μg/mL,分布半衰期t1/2α为（1.886±0.480） h,消除半衰期t1/2β为（36.473±8.324） h。本方法简便快捷,其灵敏度和准确度均可满足青春期小鼠体内DEHP代谢动力学研究。DEHP在青春期小鼠体内药物代谢动力学过程符合一级吸收二室开放模型,其分布较快,代谢较慢。     

丁香酚在罗非鱼血浆中药代动力学研究

目的在理想麻醉浓度条件下,研究丁香酚在罗非鱼血浆中药代动力学。方法选取体重为(250±10)g的罗非鱼放入丁香酚理想麻醉浓度溶液中药浴,待完全麻醉后,放入清水中复苏,幵在0～18 h间隔取样,采用液相色谱串联质谱法检测血浆中丁香酚含量, DAS2.0软件计算血浆中丁香酚药代动力学参数。结果药代动力学参数显示,丁香酚在罗非鱼血浆中最高血药浓度C_(max)为4.81mg/L,消除半衰期t_(1/2β)为2.06h,平均滞留时间(mean residence time, MRT)为3.34 h,药时曲线下面积(area under the curve, AUC)为14.55 mg/(L·h)。结论丁香酚在罗非鱼血浆中半衰期短,消除速率较快,药代参数符合二室模型。     

水解工艺对苦荞提取物中槲皮素含量的影响及其药代动力学研究

目的:以苦荞提取物为研究对象,通过正交实验设计优化苦荞提取物中芦丁被酸水解为槲皮素的工艺条件,并结合药代动力学研究探讨酸水解工艺对苦荞提取物中芦丁和槲皮素吸收的影响。方法:以盐酸百分含量、水解时间、乙醇百分含量、水解温度作为因素设计四因素三水平正交实验优化苦荞提取物中芦丁酸水解为槲皮素的工艺条件,以该工艺进行苦荞提取物酸水解,并在水解第1、2、4、6 h取样得到不同槲皮素含量的水解产物1、2、3、4。分别灌胃大鼠200 mg/kg的苦荞提取物及各水解产物,并在不同时间点采血,以黄芩素为内标,高效液相色谱(HPLC)测定血浆中槲皮素的浓度,DAS 2.0计算主要药代动力学参数。结果:苦荞提取物芦丁酸水解的最佳工艺参数为盐酸百分含量0.91%、水解时间6 h、乙醇百分含量50%、水解温度70 ℃,在该工艺条件下64.11%芦丁转化为槲皮素。苦荞提取物、水解产物1、2、3、4槲皮素的AUC_0-t分别为(17.604±5.422)、(42.175±9.435)、(87.917±19.347)、(116.706±46.256)、(178.509±49.478) mg/L·h,C_max分别为(2.743±1.217)、(7.109±2.603)、(12.438±3.197)、(15.727±4.68)、(20.044±5.736) mg/L。与苦荞提取物相比,其水解产物1、2、3、4的药代动力学参数AUC_0-t、C_max具有显著性差异(p<0.05)。结论:苦荞提取物经酸水解后部分芦丁转化为槲皮素,芦丁和槲皮素在大鼠体内的累计吸收量也相应提高。     

恩诺沙星及其代谢产物在南美白对虾体内药代动力学研究

目的研究恩诺沙星(enrofloxacin,ENR)及其代谢产物环丙沙星(ciprofloxacin,CIP)在虾体内的组织分布和药物代谢随时间的变化规律。方法在(26±2)℃的养殖水温下,以30 mg/(kg·bw)的投喂剂量对南美白对虾进行单次投喂药饵给药,采用高效液相色谱-串联质谱技术(high performance liquid chromatographytandem mass spectrometry,HPLC-MS/MS)进行测定ENR与CIP的含量,其药-时数据通过DAS 2.0动力学软件分析。结果 ENR在南美白对虾体内药时数据符合一级吸收二室模型,而其代谢产物CIP在南美白对虾体内象不符合房室模型。ENR在肝胰腺和肌肉中的最快达峰时间(T_(peak))为1和8 h,达峰浓度(C_(max))分别为24451.2和14212.1μg/kg;药时曲线下面积分别为971766.2和116847.4μg/(L·h);消除半衰期(t1/2β)分别为59.5和33.6 h。CIP在肝胰腺和肌肉中的最快达峰时间(T_(peak))为8和20 h;达峰浓度(C_(max))分别为598.8和4566.6μg/kg。肝胰腺和肌肉的ENR残留量低于最大残留限量(maximum residual limit,MRL)分别为384 h和480 h,而肝胰腺和肌肉中的CIP分别从288和480 h开始低于检出限。结论在(26±2)℃养殖水温下,以30 mg/(kg·bw)剂量对南美白对虾进行单次投饵给药时,建议休药期不得低于20 d。     

己烯雌酚及代谢物在草鱼（Ctenopharynodon idellus）体内的组织分布及药物代谢动力学研究

研究了口服灌药给药方式下,己烯雌酚及其主要代谢物双烯雌酚在草鱼(Ctenopharynodon idellus)体内的组织分布和药物代谢动力学。血浆、肌肉和肝脏中浓度-时间曲线符合一级吸收二室开放动力学模型。以1.0 mg/kg b.w.为例,己烯雌酚峰值水平肝脏最高、肌肉次之、血浆最低,平均消除速率分别为12.02μg/(L·h)、1.33μg/(kg·h)和3.59μg/(kg·h),10 h、192 h和168 h均降至检出限以下。代谢物双烯雌酚变化趋势与己烯雌酚相似,在血浆、肌肉和肝脏中1 h、6 h和6 h达到最大浓度值,8 h、168 h和144 h降至检出限以下。采用DAS2.0计算有关药物代谢动力学参数。血浆、肌肉、肝脏的AUC相差较大,不同组织对己烯雌酚的蓄积能力有所差别;血浆、肌肉和肝脏的CL/F值较小,说明其在草鱼体内分布广,消除较快。建议其消除期分别定为6 d、8 d和10 d。本研究所得的药时曲线可为草鱼己烯雌酚的消除净化提供数据支持。     

HPLC-MS/MS法测定大鼠血浆中酸枣仁皂苷A含量及其药动学研究

建立高效液相色谱-质谱串联(HPLC-MS/MS)法检测大鼠血浆中酸枣仁皂苷A的含量,并应用于药动学研究。大鼠静注(4 mg/kg)或灌胃(20 mg/kg)给药,不同时间取血,血浆样品经处理后,采用HPLC-MS/MS法测定酸枣仁皂苷A含量,色谱柱为Waters YMCTM ODS-AQ S-5 120A(2.0×100 mm)分析柱,以电喷雾离子化串联质谱(ESI)及多反应监测扫描模式(MRM)进行检测,流动相为甲醇-水(0.1%甲酸)=50∶50,流速为0.3 m L/min,柱温为30℃,根据测定结果求算药物的药动学参数。酸枣仁皂苷A在40 ng/m L~4 000 ng/m L的浓度范围内线性关系良好(r2=0.999 1),各浓度水平的精密度及稳定性的RSD均小于15%,提取回收率均大于85%。大鼠注射给药后主要药动学参数分别为Ke0.28/h,t1/22.55 h,AUC0→t2 839.89 h·ng/m L,AUC0→∞3 201.51 h·ng/m L,灌胃给药后主要药动学参数分别为Ke0.51/h,t1/21.35 h,AUC0→t206.02 h·ng/m L,AUC0→∞211.13 h·ng/m L。经计算,酸枣仁皂苷A在大鼠体内的生物利用度为1.32%。本试验所建立的检测方法快速简便、精密度好、灵敏度高及稳定性好,适用于酸枣仁皂苷A在大鼠体内血药浓度测定及药代动力学的研究。     

Reliable identification of grapevine rootstock varieties using RAPD PCR on woody samples

Since grapevine ( Vitis spp .) rootstock material is being traded increasingly as disbudded woody material a lack of distinctive morphological features on such material necessitates an alternative and reliable means of identification. Methods described here were developed for rapid and efficient extraction of DNA from woody samples rich in phenolic compounds and polysaccharides, and for subsequent identification of varieties by RAPD PCR. Using these methods, and with the application of only one selected RAPD primer, we were able to differentiate sixteen rootstock varieties, including the seven varieties most commonly used in Germany. Problems commonly encountered with reproducibility of RAPD patterns were avoided by choosing primers with a dinucleotide sequence and a high G/C content that allowed a rather high annealing temperature of 45°C. Methods described here should also be useful for other horticultural crops, especially those with woody tissues rich in phenolic compounds and polysaccharides.     

An internet compendium of analytical methods and spectroscopic information for monomers and additives used in food packaging plastics

An internet website (http://cpf.jrc.it/smt/) has been produced as a means of dissemination of methods of analysis and supporting spectroscopic information on monomers and additives used for food contact materials (principally packaging). The site which is aimed primarily at assisting food control laboratories in the European Union contains analytical information on monomers, starting substances and additives used in the manufacture of plastics materials. A searchable index is provided giving PM and CAS numbers for each of 255 substances. For each substance a data sheet gives regulatory information, chemical structures, physico-chemical information and background information on the use of the substance in particular plastics, and the food packaging applications. For monomers and starting substances (155 compounds) the infra-red and mass spectra are provided, and for additives (100 compounds); additionally proton NMR are available for about 50% of the entries. Where analytical methods have been developed for determining these substances as residual amounts in plastics or as trace amounts in food simulants these methods are also on the website. All information is provided in portable document file (PDF) format which means that high quality copies can be readily printed, using freely available Adobe Acrobat Reader software. The website will in future be maintained and up-dated by the European Commission's Joint Research Centre (JRC) as new substances are authorized for use by the European Commission (DG-ENTR formerly DGIII). Where analytical laboratories (food control or other) require reference substances these can be obtained free-ofcharge from a reference collection housed at the JRC and maintained in conjunction with this website compendium.     

Chlorohydrins of bisphenol A diglycidyl ether (BADGE) and of bisphenol F diglycidyl ether (BFDGE) in canned foods and ready-to-drink coffees from the Japanese market

BADGE.2HCl and BFDGE.2HCl were determined in 28 samples of ready-to-drink canned coffee and 18 samples of canned vegetables (10 corn, 5 tomatoes and 3 others), all from the Japanese market. HPLC was used as the principal analytical method and GCMS for confirmation of relevant LC fractions. BADGE.2HCl was found to be present in one canned coffee and five samples of corn, BFDGE.2HCl in four samples of canned tomatoes and in one canned corn. No sample was found which exceeded the 1mg/kg limit of the EU for the BADGE chlorohydrins. However the highest concentration was found for the sum of BFDGE.2HCl and BFDGE.HCl.H₂O at a level of 1.5mg/kg. A Beilstein test confirmed that all cans containing foods contaminated with BADGE.2HCl or BFDGE.2HCl had at lest one part coated with a PVC organosol.     

Aroma characterization of various apricot varieties using headspace–solid phase microextraction combined with gas chromatography–mass spectrometry and gas chromatography–olfactometry

The characterization of the aromatic profile of several apricot cultivars with molecular tracers in order to obtain objective data concerning the aromatic quality of this fruit was undertaken using headspace–solid phase microextraction (HS–SPME). Six apricot cultivars were selected according to their organoleptic characteristics: Iranien, Orangered, Goldrich, Hargrand, Rouge du Roussillon and A4025. The aromatic intensity of these varieties measured by HS–SPME–Olfactometry were defined and classified according to the presence and the intensity of grassy, fruity and apricot like notes. In the six varieties, 23 common volatile compounds were identified by HS–SPME–GC–MS. Finally, 10 compounds, ethyl acetate, hexyl acetate, limonene, β-cyclocitral, γ-decalactone, 6-methyl-5-hepten-2-one, linalool, β-ionone, menthone and (E)-hexen-2-al were recognized by HS–SPME–GC–O as responsible of the aromatic notes involved in apricot aroma and considered as molecular tracers of apricot aromatic quality which could be utilized to discriminate apricot varieties.     

European priorities for research to support legislation in the area of food contact materials and articles

A strong science base is required to underpin the planning and decision-making process involved in determining future European community legislation on materials and articles in contact with food. Significant progress has been made in the past 5 years in European funded work in this area, with many developments contributing to a much better understanding of the migration process, and better and simpler approaches to food control. In this paper this progress is reviewed against previously identified work-areas (identified in 1994) and conclusions are reached about future requirements for R&D to support legislation on food contact materials and articles over the next 5 or so years.     

Tests of potential functional barriers for laminated multilayer food packages. Part I: Low molecular weight permeants

The advent of the functional barrier concept in food packaging has brought with it a requirement for fast tests of permeation through potential barrier materials. In such tests it would be convenient for both foodstuffs and materials below the functional barrier (sub-barrier materials) to be represented by standard simulants. By means of inverse gas chromatography, liquid paraffin spiked with appropriate permeants was considered as a potential simulant of sub-barrier materials based on polypropylene (PP) or similar polyolefins. Experiments were performed to characterize the kinetics of the permeation of low molecular weight model permeants (octene, toluene and isopropanol) from liquid paraffin, through a surrogate potential functional barrier (25 μm-thick oriented PP) into the food simulants olive oil and 3% (w/v) acetic acid. These permeation results were interpreted in terms of three permeation kinetic models regarding the solubility of a particular model permeant in the post-barrier medium (i.e. the food simulant). The results obtained justify the development and evaluation of liquid sub-barrier simulants that would allow flexible yet rigorous testing of new laminated multilayer packaging materials.     

Textural Properties of Cold-set Gels Induced from Heat-denatured Whey Protein Isolates

A 9% whey protein (WP) isolate solution at pH 7.0 was heat-denatured at 80°C for 30 min. Size-exclusion HPLC showed that native WP formed soluble aggregates after heat-treatment. Additions of CaCl2 (10–40 mM), NaCl (50–400 mM) or glucono-delta-lactone (GDL, 0.4–2.0%, w/v) or hydrolysis by a protease from Bacillus licheniformis caused gelation of the denatured solution at 45°C. Textural parameters, hardness, adhesiveness, and cohesiveness of the gels so formed changed markedly with concentration of added salts or pH by added GDL. Maximum gel hardness occurred at 200 mM NaCl or pH 4.7. Increasing CaCl2 concentration continuously increased gel hardness. Generally, GDL-induced gels were harder than salt-induced gels, and much harder than the protease-induced gel.     

Influence des ions sur le pouvoir hydratant de l'ure e: e tude sur peau de porc ex vivo

This study deals with the influence of ions (NaCl and MgSO4) in a W/O emulsion containing 10% urea. Moisturization kinetics are assessed by corneometry on pig skin ex vivo. The formula's influence on urea penetration is measured by infrared spectrometry with an ATR device and the stripping method. Corneometry and spectroscopy were chosen to record simultaneously the hydratation levels and urea localization into superficial cell layers. Urea crystallization after evaporation of emulsions and aqueous solutions is described. Results show that urea does not hydrate nor penetrate when applied to the skin through an aqueous gel. In a W/O emulsion, sodium chloride increases the ability of urea to moisturize without improving penetration. In vitro urea crystallization is disturbed by sodium chloride or magnesium sulphate for solutions and emulsions. This stabilization by ions is correlated with good moisturization values. The stabilization of urea in the solute state provided by ions increases its water epidermal binding capacity without enhancing penetration.     

Occurrence of bisphenol-F-diglycidyl ether (BFDGE) in fish canned in oil

The levels of bisphenol-F-diglycidyl ether (BFDGE) were quantified as part of a European survey on the migration of residues of epoxy resins into oil from canned fish. The contents of BFDGE in cans, lids and fish collected from all 15 Member States of the European Union and Switzerland were analysed in 382 samples. Cans and lids were separately extracted with acetonitrile. The extraction from fish was carried out with hexane followed by re-extraction with acetonitrile. The analysis was performed by reverse phase HPL C with fluorescence detection. BFDGE could be detected in 12% of the fish, 24% of the cans and 18% of the lids. Only 3% of the fish contained BFDGE in concentrations considerably above 1mg/kg. In addition to the presented data, a comparison was made with the levels of BADGE (bisphenol-A-diglycidyl ether)analysed in the same products in the context of a previous study.