头孢丙烯中有关物质检查的HPLC法

目的：建立头孢丙烯中有关物质的检测方法。方法：采用高效液相色谱法,固定相为C18柱,流动相为乙腈-磷酸二氢铵溶液（10：90）,检测波长为280nm。结果：头孢丙烯与各有关物质达到了较好的分离,顺式异构体和反式异构体峰的相对保留时间分别为0．7和1．0,分离度大于2．5。3批样品的中间体杂质含量分别为0．14％、0．15％和0．15％,其它最大单个杂质含量分别为0．38％、0．39％和0．36％,杂质总量分别为1．20％、1．15％和1．18％。结论：本法简便、专属性强、准确度高、重复性好,可用于测定头孢丙烯中的有关物质。     

阿莫西林—舒巴坦匹酯片含量及有关物质质控分析方法的建立

目的:测定阿莫西林-舒巴坦匹酯片的含量及有关物质。方法:反相离子对高效液相色谱法。色谱条件:ODS柱,流动相为0.01mol·L~(-1)SDS(pH 2.5)-甲醇(45:55),流速为1.0mL·min~(-1),检测波长230nm。结果:舒巴坦匹酯和阿莫西林的线性范围分别为11.0～0.125mg·mL~(-1)和0.25～0.015 mg·mL~(-1),回收率分别为98.9％和98.5％,RSD分别为1.5％和1.6％(n=5)。阿莫西林和舒巴坦匹酯的相对吸收系数比为19.6。结论:该方法能简单、快速、准确地同时测定阿莫西林和舒巴坦匹酯的含量和有关物质。     

RP-HPLC法测定硝唑尼特含量及有关物质的方法学研究

目的:反相高效液相色谱法测定硝唑尼特的含量及其有关物质。方法:C18色谱柱(4.6 mm×150mm,填料:Hypersil,粒度:5μm),以乙腈-10 mmol·L-1甲酸(60:40)为流动相,流速0.8 mL·min-1,波长240 nm测定。结果:反相高效液相色谱法测定的线性范围为20.0-120.0μg·mL-1,相关系数为0.9998;最低检测限1.0 ng;样品溶液至少在24 h内稳定(RSD<1.0％);进样精密度(RSD<0.1％)良好。结论:本法简便、快速、准确,可用于硝唑尼特含量及其有关物质的测定。     

RP-HPLC法测定头孢丙烯分散片中头孢丙烯的含量

目的:建立测定头孢丙烯分散片中头孢丙烯含量的方法。方法:采用反相高效液相色谱法。色谱柱为HypersilC18柱,流动顺式相异为构乙体腈检-磷测酸浓二度氢在铵0溶.05液0(～105.∶68050)m,检g·测mL波-长1范为围2内80,n头m孢,流丙速烯为反1式.0异m构L·体m检in-测1,浓进度样在量0为.01100～μL0,.1柱00温m为g·2m5L℃-1。范结围果内:,头均孢与丙各自烯峰面积积分值呈良好的线性关系;头孢丙烯顺式和反式异构体的平均回收率分别为99.72%和99.26%,RSD分别为1.71%和2.30%。结论:本方法准确、简便,可用于头孢丙烯分散片的质量控制。     

更昔洛韦含量及有关物质的HPLC测定

目的:改进更昔洛韦含量及有关物质的测定方法。方法:采用高效液相色谱法测定更昔洛韦的含量及有关物质,并与薄层色谱法和非水滴定法测定含量和有关物质的结果进行比较。结果:高效液相色谱法:更昔洛韦与其鸟嘌呤、异构体及其他降解产物分离度良好,含量测定在0.01～0.15 mg·mL~(-1)的浓度范围内线性良好(r=0.9999)。结论:高效液相色谱法与薄层色谱法及非水滴定法的测定结果基本一致,高效液相色谱法简便、专属性强,更适用于更昔洛韦含量及有关物质的测定。     

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。     

HPLC法测定多尼培南原料药含量及有关物质

目的:建立测定多尼培南原料药含量及有关物质的方法。方法:采用高效液相色谱法。色谱柱为ApolloC18,流动相为甲醇-0.02mol·L-1KH2PO4(H3PO4调pH至3.0)=12∶88,主药与有关物质检测波长分别为297、220nm,流速为1.0mL·min-1,柱温为30℃,进样量为20μL。结果:多尼培南检测浓度线性范围分别为20.0～200.0μg·mL-(1r=0.9999),平均回收率为101.39%(RSD=0.63%,n=9),检测限为20ng·mL-1。结论:该方法简便、灵敏度高、重复性好,可用于多尼培南原料药含量测定和有关物质检查。     

RP-HPLC法测定氢溴酸加兰他敏口服液含量及有关物质

目的:采用反相高效液相色谱法测定氢溴酸加兰他敏的含量及其有关物质。方法:采用Kromasil C_(18)色谱柱(5 μm,4.6mm×150 mm);以乙腈-水相(20:80,每 800 mL水相中含有2.67 mL 二丁胺,用磷酸调节pH为 9.0±0.05)为流动相;流速1.0 mL·min~(-1);检测波长:280 nm;柱温:室温;进样量:20 μL。结果:反相高效液相色谱法测定的线性范围为30～210 μg·mL~(-1);r=0.999 9;日内精密度:RSD为0.73％(n=5);日间精密度:RSD为0.72％(n=5),氢溴酸加兰他敏含量测定高、中、低3种浓度的回收率分别为98.89％、99、84％和99.56％,RSD分别为0.53％、0.40％和0.49％。结论:本法简便快速、准确、专属性好。     

HPLC法测定地巴唑片含量及其有关物质

目的:建立高效液相色谱法测定地巴唑片的含量及其有关物质。方法:采用Shimadzu C18色谱柱(4.6 mm×150 mm,5μm);以甲醇-水-三乙胺-冰醋酸(60:40:0.5:0.5)为流动相;流速1.0 mL·min-1;检测波长272 nm。结果:地巴唑的线性范围为16-48/μg·mL-1,r=0.9999;平均回收率为99.83％,RSD为0.62％;最低检测限为1.6 ng;最低定量限为5.2 ng。结论:本法简便、快速、准确,适用于地巴唑片的含量与有关物质测定。     

HPLC法测定盐酸洛贝林注射液中的有关物质

目的:采用反相高效液相色谱法测定盐酸洛贝林注射液中的有关物质.方法:采用反相高效液相色谱法,C18柱,流动相为0.05 mol·L-1磷酸二氢钾溶液(用磷酸调节pH值至3.0)-甲醇(55:45)为流动相;检测波长为210nm.结果:盐酸洛贝林注射液中除主峰(顺式洛贝林)外,出现一较大含量的色谱峰,为洛贝林的异构体(反式洛贝林);盐酸洛贝林与其他杂质分离良好,样品溶液在8 h内稳定;结论:所建方法能有效地分离盐酸洛贝林注射液中的有关物质,方法简单、可靠.     

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.

---

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.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.