纸基质室温Lin光法研究氧氟沙星体内药代动力学

本文建立了滤纸基质室温Lin光（PS－RTP）法测定人尿中氧氟沙星含量的新方法,并将该法用于人尿中氧氟沙星回收率和排出速率的测定,实验表明：氧氟沙星在尿液中的平均回收率为99．1％,相对标准偏差RSD＜1．7％。给药后24h内的排泄率为77．7％,氧氟沙星最大药物浓度出现的时间为2．5－4h。     

毛细管电泳-电化学发光法研究阿莫西林在人尿中的药代动力学

建立了毛细管电泳一电化学发光(CE-ECL)法测定人尿中阿莫西林的新方法,并将该方法用于人尿中阿莫西林药代动力学的研究.结果表明:阿莫西林在尿液中平均回收率为95.35%,该方法的线性范围为0.001～5.0μg/mL,检出限(3σ)为0.32ng/mL,对1.0μg/mL阿莫西林连续测定6次,其相对标准偏差小于2.0%.给药后6 h内的排泄率为44.54%,人尿中阿莫西林最大药物浓度出现时间为1.0～1.5 h.本方法用于人尿中阿莫西林药代动力学的研究具有快速、简便、灵敏、样品用量少等特点.     

气相色谱电子捕获检测法测定人尿中氟硝西泮的代谢物7-氨基氟硝西泮

采用气相色谱电子捕获检测法测定人尿中氟硝西泮的代谢物 7 氨基氟硝西泮。测定时尿中加入内标 7 氨基硝西泮 ,用β 葡萄糖醛酸苷酶水解及碱性液液萃取 ,再用七氟丁酸酐衍生化。尿中 7 氨基氟硝西泮提取率为 96.8% ;回收率为 98.6± 3 .4% (平均值±SD) ;检出限为 1 .2 μg L ,对口服治疗量氟硝西泮的人尿进行检测 ,可检出服药后 60h尿中的 7 氨基氟硝西泮。     

进食对左氧氟沙星在人体内代谢的影响

测定进食前后口服左氧氟沙星的尿药浓度，分析进食对左氧氟沙星在人体内代谢的影响。将受试者的尿液用0．01moL／L盐酸溶液稀释，用紫外分光光度法在326nm波长处测定左氧氟沙星的含量。左氧氟沙星的平均回收率为96．35％，线性范围为5．06～25．28μg／mL，测定结果的相对标准偏差为1．61％。健康受试者分别于进食前后口服左氧氟沙星，48h后尿药排泄量分别为给药量的87．43％和83．74％，经统计学分析无显著性差异，表明进食对左氧氟沙星在人体内的代谢没有显著影响。     

HPLC法测定人房水中氧氟沙星的含量

建立人房水中氧氟沙星的高效液相色谱测定法.取房水100 μL,加甲醇去蛋白后,进高效液相色谱分析.色谱条件:色谱柱为Agilent ZORBAX SB-C18(4.6× 150 mm,5μm),柱温25℃,流动相为乙腈-0.4%磷酸(三乙胺调pH 3.5)(13:87),流速1.0 mL/min,检测波长295 nm.氧氟沙星和内标的保留时间分别为7.98和9.55 min,氧氟沙星的线性范围为0.1～2.5μg/mL,回归方程为Y=2.47X+0.08,r=0.9996.低中高三个质控样品的日内精密度(RSD)分别为1.89%,1.71%,1.48%,日间精密度(RSD)分别为3.74%,2.40%,1.75%,方法回收率分别为99.43%,101.4%,101.4%,最低检测浓度为0.01μg/mL.本法操作简单,方法准确,可用于房水中氧氟沙星的含量测定.     

毛细管电泳与电致化学发光结合用于人尿中甲磺酸培氟沙星的测定研究

基于甲磺酸培氟沙星(PM)对三联吡啶钌在铂电极上的电致化学发光信号有增敏作用,与毛细管电泳结合,建立了一种研究PM药代动力学的新方法.在最佳条件下,该药物在0.05 ～10 mg/L范围内峰高与PM浓度呈良好的线性关系,方法检出限为0.006 mg/L,峰高相对标准偏差为2.4%(n=6),尿样回收率在 93% ～112%之间.该方法用于人尿中PM的排泄速率测定,1.5 ～2 h内平均排泄速率最大,48 h内原型药物排泄率为13.5%.     

蛋白质印迹模板的制备及在尿液蛋白测定中的应用

以牛血清蛋白(BSA)为分子模板,甲基丙烯酸(MAA)为功能单体,乙二醇二甲基丙烯酸酯(EDGMA)为交联剂,偶氮二异丁腈(AIBN)为引发剂,制备了BSA分子印迹模板,研究了该模板对BSA的吸附性能,并以其作为净化材料去除人尿中的干扰物质,测定了人尿中的蛋白质。结果表明:蛋白质模板吸附和洗脱的最佳pH值分别为5.3和5.6,最佳吸附时间为2h,最大吸附容量为72mg/g。三种人尿样品中蛋白质的含量分别为35.4、18.9、24.2mg/L,回收率为92.4%~103.7%。该方法可用于人尿中蛋白质含量的测定。     

石墨炉原子吸收光谱法测定尿样中铅

石墨炉原子吸收光谱法测定尿铅以钯溶液与抗坏血酸溶液作为混合基体改进剂,使灰化温度达到1000℃以上,降低了尿中复杂成分的干扰.方法的检出限为0.20μg·L-1,对正常人混合尿中铅测定结果的相对标准偏差为2.54%～4.86%,加标回收率为92.6%～112.6%.     

高效液相色谱法测定氧氟沙星胶囊中氧氟沙星的含量

建立测定氧氟沙星胶囊中氧氟沙星含量的高效液相色谱法。选用AgilentEclipseXDBC8柱(250mm×4.6mmi.d.,5μm)及LabAllianceC8保护柱(10mm×4.6mmi.d.,5μm),流动相为乙腈-水(体积比为25∶75,含20.0mmol/L磷酸二氢钾及0.2%三乙胺,用0.2%磷酸溶液调至pH=5.50),流动相流速为1.0mL/min,检测波长为293nm,进样量为20μL,外标法定量。测定氧氟沙星胶囊中氧氟沙星含量的线性范围为1.00～200μg/mL(r=0.9998),回收率为98.8%～100.7%,测定结果的相对标准偏差为0.75%～1.17%(n=5)。     

铁络合光度法测定氧氟沙星和诺氟沙星含量

研究了氧氟沙星、诺氟沙星与Fe(III)在室温下的络合反应.在酸性介质中,氧氟沙星、诺氟沙星与Fe(III)形成的黄色配合物最大吸收波长为436nm;氧氟沙星和诺氟沙星的浓度分别在2.24~192mg/L和8.0~248mg/L范围内与体系的吸光度呈良好的线性关系,其线性回归方程分别为:A=0.009 06+0.005 7 c(c,mg/L;r=0.999 3;氧氟沙星)和A=0.001 23+0.003 04 c(c,mg/L;r=0.999 8;诺氟沙星),方法的检出限分别为0.41和0.76mg/L.对浓度均为64.0mg/L的氧氟沙星和诺氟沙星平行测定11次,其相对标准偏差分别为0.6%和0.8%.应用拟定的方法对氧氟沙星和诺氟沙星药物制剂中主成分的含量进行了测定,回收率在99.7%~104.7%范围内.     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

Different approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

A general and convenient synthesis of 4-(tosylmethyl)semicarbazones and their use in amidoalkylation of hydrogen,heteroatom, and carbon nucleophiles

A general synthesis of previously unknown semicarbazone-based α-amidoalkylating reagents, 4-(tosylmethyl)semicarbazones, has been developed. The synthesis involved three-component condensation of semicarbazones of aliphatic or aromatic aldehydes with the same or other aldehydes and p-toluenesulfinic acid. The scope and limitations of this reaction were investigated. The compounds obtained were demonstrated to be an efficient α-(4-semicarbazono)alkylating agents. They were reacted with H- (sodium borohydride), O- (sodium methylate), S- (sodium phenylthiolate), N- (pyrrolidine, sodium succinimide), P- (trialkyl phosphites), and C-nucleophiles (sodium diethyl malonate) to give the corresponding products of the tosyl group substitution, 4-substituted semicarbazones, including analogues of nitrofurazone. Among the prepared compounds tested in vitro for antibacterial and antifungal activity, three nitrofuryl-containing semicarbazones exhibited high biological activities with minimum inhibitory concentration (MIC) values of 8–32 μg/mL.     

Synthesis of novel chiral bidentate hydroxyalkyl-N-heterocyclic carbene ligands and their application in palladium-catalyzed Mizoroki–Heck couplings and asymmetric addition of diethylzinc to benzaldehyde

A small library of new chiral bidentate hydroxyalkyl-imidazolium salts 1 is conveniently synthesized on multi-gram scale from inexpensive and commercially available chiral pool amino acids. The corresponding carbenes, generated by deprotonation of imidazolium salts 1, in combination with palladium(II) chloride were tested in the Mizoroki–Heck coupling reaction. The most significant results in terms of yields and reactivities were achieved with low catalyst loading. The catalytic activities of these imidazolium salts were also investigated in the asymmetric addition of diethylzinc to benzaldehyde. The use of MgO nanoparticles as an additive in conjunction with these ligands played a crucial role in increasing the efficiency of these reactions.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.