测定抗焦虑新药的大鼠血药浓度的GC—MS法

目的 :建立用气 -质联用仪测定抗焦虑新药 (AF - 5 )的血药浓度的分离分析方法 ,并对AF - 5不同剂型的血药浓度进行测定。方法 :血浆样品经正己烷一石油醚 (9∶1)提取 ,以高纯氦为载气 ,DB - 5MS毛细管柱 ,正二十一烷为内标进行定性定量分析。结果 :检测限为 0 0 5 6ng (S N =6 ) ,最低检测浓度为 8 5ng·mL- 1 血浆。AF - 5的血药浓度在 8 5～ 110 0ng·mL- 1 范围内线性关系良好。回收率为 81 6 %。结论 :该方法操作简便 ,特异性强 ,重现性好 ,适用于药代动力学研究和血药浓度监测。     

RP—HPLC法测定人唾液中依诺沙星浓度

目的:建立测定人唾液中依诺沙星浓度的RP-HPLC法。方法:采用Shim-pack CLC-ODS柱,以甲醇-0.1 mol·L~(-1)柠檬酸(28:72)为流动相,吡哌酸为内标;检测波长为266nm;流速1.0mL·min~(-1) ;柱温为室温;进样量:20μL。根据唾液药物浓度求算9名健康志愿者单剂量口服依诺沙星胶囊的药动学参数。结果:依诺沙星与样品中杂质以及内标分离完全;在0.1～10.0μg·mL~(-1)范围内,依诺沙星和内标峰高比与其浓度线性关系良好(r=0.999 6);样品平均回收率为99.81％;日内RSD=2.8％,日间RSD=4.8％。依诺沙星在人体内的T_(1/2ke),Tin_(max)和CL·F~(-1)分别为4.05h,1.54h,31.25 L·h~(-1),与由血药浓度求算的药动学参数接近。结论:该法简便、快速、专一性强,适用于依诺沙星唾液药物浓度测定及药动学研究之用。     

1—乙酰基—3—邻甲基苯甲酰基—5—氟尿嘧啶含量及其杂质的高效液相色谱测定

目的:采用高效液相色谱法测定1-乙酰基-3-邻甲基苯甲酸基-5-氟尿嘧啶的含量及其有关物质。方法:以菲为内标物质,采用氰基柱(4.6mm×200mm,Nucleosil填料,粒度5μm),以5％冰醋酸乙腈溶液-0.5％醋酸铰溶液(60:40)为流动相,流速为1mL·min~(-1) ,紫外检测器在254nm处测定。结果:线性范围为0.2～1μg,r=0.999 9;平均回收率为99.9％;供试品溶液在2h内稳定;日内和日间测定的RSD分别为0.8％(n=6)和1.1％(n=5);杂质检出限为0.08ng。结论:采用高效液相色谱法测定1-乙酰基-3-邻甲基苯甲酰基-5-氟尿嘧啶的含量及其有关物质,方法简便准确,结果可靠。     

氯仿萃取-分光光度法测定β-胡萝卜素含量

目的:建立氯仿萃取-分光光度法测定β-胡萝卜素水溶性制剂中β-胡萝卜素的含量方法.方法:将样品经氯仿分步萃取后,以环己烷为溶剂,在455±1nm波长处,用分光光度法测定A值.结果β-胡萝卜素浓度在1. 60～3.20μg·ml~(-1)时,吸收值与浓度呈线性关系,相关系数(r=0.9998,平均回收率为99.9%,RSD为0.74%(n= 5.结论:本方法可行,测定结果准确,精密度,适用于β-胡萝卜素水溶性制剂中β-胡萝卜素的含量测定.     

HPLC测定猪血浆和胰腺组织中的5-FU及其在胰腺癌区灌注化疗效果评价中的应用

目的　采用HPLC测定猪血浆及其胰腺组织中 5 -氟尿嘧啶 (5 -FU)的浓度 ,研究猪不同部位给予 5 -FU后血浆及组织中的浓度差异。方法　以C1 8-A柱为固定相 ,水 (pH 2 .0 ) -甲醇 (95∶5)为流动相 ,2 66nm检测。用建立的方法测定了 1 4只健康幼猪分别自十二指肠动脉、脾动脉及左耳缘静脉途径滴注 5 -FU后血浆及胰腺组织中 5 -FU的浓度 ,以配对t检验比较不同部位给药后血浆及胰腺组织中 5 -FU的浓度差异。结果　所建立的方法浓度在 0 .5～ 2 0 μg·ml- 1 范围内线性关系良好 (r =0 .9993) ,平均血浆回收率为 99.2 % ,RSD =5 .5 % ;平均组织回收率为 96 .2 % ,RSD =4.5 %。测得经十二指肠动脉或脾动脉途径滴注 5 -FU与经左耳缘静脉全身化疗相比极大地增高了胰腺组织内的 5 -FU浓度 ,显著降低灌注期间周围循环血中的药物浓度。结论　该方法简便、杂质干扰少 ,结果准确。 5 -FU经局部灌注用药有利于提高胰腺组织中的浓度     

生物分析法测定人血浆D-聚甘酯

目的:建立测定人血浆中D-聚甘酯的生物分析法。方法:应用 aPTT试剂盒,采用免疫荧光比浊法在 ACL futura plus全自动血凝仪上进行自动定量分析,aPTT来检测血浆中D-聚甘酯浓度,考察其线性范围、精密度及回收率等。结果:D-聚甘酯在0.05～10.0 mg·L~(-1)血浆浓度范围内线性关系良好(r=0.9957,n=10),最低检测浓度为 0.05 mg·L~(-1)。1.0,5.0,10.0 mg·L~(-1)3个浓度的回收率分别为 91.48％,97.56％,105.67％,RSD均小于 14％。这 3个浓度日内及日间 RSD(n=5)分别为 10.63％,5.73％,1.58％和12.91％,9.42％,7.19％。结论:建立的D-聚甘酯生物测定方法操作简便,结果灵敏、准确、可靠,可进一步用于该药的药代动力学研究。     

气相色谱—电子捕落法测定阿那曲唑血药浓度

目的：建立测定人血浆中阿那曲唑药物浓度的GC-ECD方法。方法：以安定为内标，用乙醚一次提取。HP-50毛细管柱测定。结果：检测浓度在0.5-20ug.L^-1内，线性方程为Y=0.0178c-0.0284,r=0.9998。方法回收率平均为97.54%。3种浓度1.9,10.0,20.0ug.L^-1提取回收率分别为84.54%,93.94%,97.03%;日内、日间精密度分别为4.79%,2.13%,1.71%及6.70%,2.96%,4.17%(n=5)，在志愿者单剂量口服阿那曲唑1mg后，0.33-106h内血药浓度范围在1.27-10.19ug.L^-1。结论：该法简便、准确、灵敏，可用于测定该药在人血浆中的药物浓度。     

RP-HPLC法同时测定血浆中艾司唑仑和阿普唑仑的浓度

目的　建立反相 HPL C法同时测定血浆中艾司唑仑 (EZ)和阿普唑仑 (AZ)浓度的方法。 方法 　以 Techsphere-ODS色谱柱为分析柱 ,甲醇 -水 (65∶ 3 5 )为流动相 ,硝西泮 (NZ)为内标 ,紫外 2 5 4nm处检测。结果 　 EZ和 AZ血浓线性范围为 0 .2 5～ 3 .0μg· ml- 1 ,最低检测浓度分别为 12 .5 ng/ml、12 .5 ng/ml,日内和日间精密度均小于 7%,平均回收率分别为 10 1.5 0 %,96.14 %。 结论 　本法可用于临床血药浓度测定     

混合取代基—β—环糊精—毛细管电泳法分离测定麻黄碱和伪麻黄碱

目的:建立毛细管电泳法同时分离测定同分异构的2对手性化合物麻黄碱和伪麻黄碱的含量。方法:Waters CapillaryIon Analyzer,50μm×60cm空心熔融石英毛细管柱,柱上紫外检测。电泳条件:分离用缓冲液为25mmol·L~(-1)的磷酸-Tris 缓冲液,含18mmol·L~(-1)的羧甲基-β-环糊精和7.5mmol·L~(-1)的β-环糊精-硫酸酯,pH3.02。分离电压:18kV;温度:25℃;虹吸进样,高度10cm,时间1s;紫外检测波长214nm。结果:左旋伪麻黄碱、右旋麻黄碱、左旋麻黄碱和右旋伪麻黄碱线性范围分别为23.7～237μg·ml~(-1),25.0～250μg·mL~(-1),25.0～250μg·mL~(-1),25.4～254μg·mL~(-1),以信噪比等于3:1为标准,最小检测浓度均为5.0μg·mL~(-1);日内和日间精密度RSD在2.4％～4.3％之间。结论:方法分离效率高、简便、快速、成本低。     

高效液相色谱法测定L—谷氨酰胺及其制剂的含量

目的:采用HPLC方法测定L-谷氨酰胺及其制剂的含量。方法:采用NUCLEOSIL 5NH_2100A(250mm×4.6mm)色谱柱,乙腈-0.05mol·L~(-1) 磷酸二氢钾缓冲液(pH4.0)(70:30)为流动相,流速1mL·min~(-1),检测波长215nm。结果:在5～50μg范围内,色谱峰面积与对照品浓度呈现良好的线性关系,r=0.9999;平均回收率分别为99.79％(RSD=0.43％,n=5),99.44％(RSD=0.30％,n=5)。结论:该方法简便准确,重现性好,在本色谱条件下L-谷氨酰胺与其分解产物能够得到很好的分离,可以准确测定L-谷氨酰胺的含量,也可用于原料及制剂有关物质的限度检查。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.