气相色谱法测定阿立哌唑原料药中4种有机溶剂残留量

目的 建立阿立哌唑原料药中残留有机溶剂乙醇、乙腈、二氯甲烷、N,N-二甲基甲酰胺的气相色谱测定方法 .方法 采用AC-1毛细管色谱柱(30m×0.53mm×1.0μm);氮气为载气;初始柱温为40℃,保持3min后以40℃/min的速率升至160℃,保持2min;氢火焰离子化检测器温度为200℃;进样口温度为160℃;进样量为1μL.结果 阿立哌唑原料药中的4种有机溶剂完全分离,在所考察的浓度范围内均具有良好的线性关系,加样回收率在98.1%~99.0%范围内.3批阿立哌唑样品中均未检出4种有机溶剂.结论 该方法 准确、灵敏度高,适用于阿立哌唑原料药中有机溶剂残留量的测定.     

气相色谱法测定新型抗癌化合物二-(2,4-二氟苯甲酰异羟肟酸)二苯基合锡中有机溶剂残留量

目的:建立测定抗癌原料药二-(2,4-二氟苯甲酰异羟肟酸)二苯基合锡(DPDFT)中的有机溶剂残留量的方法。方法:采用毛细管气相色谱法,FID检测器,Agilent HP-5(30 m×0.32 mm×0.25μm)毛细管柱,柱温30℃,进样口温度为200℃,检测器温度为220℃,流速为31.90 mL.min-1,分流比为20∶1,以1,2-二氯乙烷为内标,甲苯为溶剂,测定有机溶剂残留量。结果:甲醇、正己烷、醋酸乙酯在考察的浓度范围内线性关系良好,线性范围分别为150～450μg.mL-1(r=0.999 7),14.5～43.5μg.mL-1(r=0.999 9),250～750μg.mL-1(r=0.999 9),平均加样回收率分别为99.6%(RSD=1.0%),100.0%(RSD=1.5%),99.0%(RSD=1.0%)。结论:该方法快速、简便、结果准确,可用于二-(2,4-二氟苯甲酰异羟肟酸)二苯基合锡中的有机溶剂残留量的测定。     

气相色谱法测定伊曲康唑传递体有机溶剂残留量

目的建立测定伊曲康唑传递体中有机溶剂残留量的气相色谱法。方法采用气相色谱法,FID检测器,DB-624(30 m×0.32 mm,1.8μm),载气为氮气,程序升温,进样口温度200℃,检测器温度260℃,以二甲亚砜为溶剂配制对照溶液及供试品溶液。结果两种有机溶剂完全分离,在所考察的浓度范围内具有良好的线性关系,乙醇、三氯甲烷的检测限分别为1.58和2.968μg.mL-1,精密度RSD均<1.0%。平均回收率98%～101%。结论该方法简便灵敏,结果准确可靠,适用于伊曲康唑传递体原料药中有机溶剂残留量检测。     

GC测定抗癌原料药二氯二茂钛中有机溶剂残留量

目的 建立毛细管气相色谱法测定有机金属抗癌原料药二氟二茂钛中的有机溶剂残留量.方法采用HP-5(5%苯基甲基聚硅氧烷)毛细管色谱柱,FID检测器.载气为N2,柱温为45℃,检测器温度为160℃,流速为1.2 mL·min-1,分流比为201,正已烷为内标进行测定.结果三氯甲烷和四氢呋喃的线性范围分别为0.399～319.2μg·mL-1和6～48μg·mL-1,平均回收率为96.7%和102.3%(n=9);RSD分别为1.6%和1.1%(n=9);最低检测限分别为0.23μg·mL-1和0.9μg·mL-1.结论 方法操作简便、准确、灵敏度高、重复性好,适用于二氯二茂钛原料药中有机溶剂残留量的测定.     

气相色谱法测定美洛昔康中有机溶剂残留量

目的 建立测定美洛昔康中有机溶剂残留量的方法.方法 气相色谱法,PEG-20M(30m×0.32mm,0.25μm)弹性石英毛细管柱,氢火焰离子化检测器,柱温:35℃(恒温5min),以10℃·min-1的升温速率至140℃(恒温2min);以20℃·min-1的升温速率至220℃(恒温5min).进样口温度:250℃;检测器温度:250℃;载气:氮气;进样方式:直接进样法;进样量:1μL.结果 4种溶剂的回收率在100.0%～101.5%之间,相对标准偏差均小于2%,最低检出限为1.0×10-3 μg·mL-1～5.0×10-3 μg·mL-1.结论 本方法准确、简便、快捷,可用于美洛昔康中的有机溶剂残留测定     

毛细管气相色谱法测定达沙替尼原料药中6种残留溶剂

目的：建立毛细管气相色谱测定达沙替尼原料药中吡啶、二氯甲烷、甲醇、N,N-二甲基甲酰胺、二甲亚砜、乙醇6种有机溶剂残留量的方法。方法采用DB-624(30 m×0.53 mm,3μm)毛细管柱;氢火焰离子化检测器;程序升温：初始温度25℃(维持13 min),再以15℃·min-1升至150℃(维持5 min),再以40℃·min-1升至220℃(维持5 min);载气为氮气;柱流速为2.0 mL·min-1;进样口温度：230℃;检测器温度：250℃;分流直接进样,以N,N-二甲基乙酰胺为溶剂,进样体积为0.5μL。结果6组分均能良好分离,6组分峰面积与浓度均呈良好的线性关系,其中吡啶、二氯甲烷、甲醇、N,N-二甲基甲酰胺、二甲亚砜、乙醇的线性范围分别为4.16~31.21μg·mL-1(r=0.9998),12.12~90.92μg·mL-1(r=0.9994),59.98~449.85μg·mL-1(r=0.9998),18.16~136.19μg·mL-1(r=0.9993),100.25~751.86μg·mL-1(r=0.9991),100.30~752.28μg·mL-1(r=0.9999),平均回收率为98.4％~101.3％(RSD=2.8％~5.0％)。结论该方法简单、灵敏、准确,可用于测定达沙替尼原料药中的残留溶剂。     

氢溴酸高乌甲素中有机溶剂残留量HL-GC 检测方法的建立

目的：建立测定氢溴酸高乌甲素中4种有机溶剂残留量的顶空毛细管气相色谱方法。方法采用DB-624毛细管柱（30 m ×0.53 mm,3μm）,程序升温,起始柱温40℃,维持7 min,以25℃·min-1的速率升至200℃,维持1 min;进样口温度：200℃;FID 检测器,检测器温度：250℃;进样方式：顶空进样,平衡温度：80℃,平衡时间：30 min;载气为N2;以DMF为溶剂对氢溴酸高乌甲素中乙醇、乙酸乙酯、三氯甲烷和苯的残留量进行测定。结果4种有机溶剂分离度良好,乙醇、乙酸乙酯、三氯甲烷和苯浓度分别在129.2-1033μg·mL-1（r=0.999）、120.5-964.2μg·mL-1（r=0.999）、3.32-26.5μg·mL-1（r=0.998）、0.14-1.13μg·mL-1（r=0.997）范围内线性关系良好;平均回收率（n=9）分别为97.4%、97.4%、96.8%、98.1%,RSD 分别为1.3%、2.0%、1.7%、3.1%。结论本文建立的顶空毛细管气相色谱法,经方法学验证可用于氢溴酸高乌甲素中有机溶剂残留量的测定,可作为该药质量标准修订的参考。     

顶空气相色谱法测定盐酸左布比卡因中残留溶剂

目的:建立盐酸左布比卡因原料药中有机溶剂残留量的测定方法.方法:采用内标法项空进样毛细管气相色谱法,测定盐酸左布比卡因原料中有机溶剂残留量.色谱柱为DB - 624毛细管柱(30m×0.53mm,3.0μm),载气为氮气,FID检测器;程序升温,在60℃下保留5min,然后以20℃/min的速率升温至200℃,保持10min;进样口温度220℃,检测器温度240℃,分流比为1∶1.结果:质量浓度在范围内与峰面积线性关系良好,r为0.999 98,平均回收率为103.2％,精密度的RSD为0033％,最低栓出限为0.14μg/mL.结论:该方法可用于盐酸左布比卡因中有机溶剂残留量的测定.     

气相色谱法测定荧光素钠原料药中的残留溶剂

目的建立气相色谱法测定荧光素钠原料药中残留溶剂。方法选用毛细管柱DB-WAX(30.0m×0.25mm×0.25μm),氢火焰离子化检测器(FID),色谱条件:初温60℃(保持10min),以100℃·min-1升至200℃(保持1min),进样口温度:230℃,检测器温度:250℃。选择正丙醇作为内标,进样量1μL。结果二氯甲烷在(62.97~176.31)μg·mL-1浓度范围内与峰面积/内标峰面积比值呈良好的线性关系,检测限为25.19μg·mL-1,溶剂和内标对测定无干扰,3批样品均未检出二氯甲烷。结论经方法学验证,本方法简便灵敏,准确,可用于荧光素钠原料药中残留溶剂的检测。     

气相色谱法测定比沙可啶原料药中残留的N,N-二甲基甲酰胺

目的 采用直接进样气相色谱法测定比沙可原料药中N,N-二甲基甲酰胺(DMF)的残留量.方法 采用DB-624毛细管色谱柱(60.0 m×0.53 mm,3.0 μm),进样口温度230℃,氢火焰离子化检测器温度250℃,程序升温:初始温度90℃,保持10 min,以40 ℃·min-1速率升温至190℃,载气为氮气,流速3.0 mL· min-1;直接进样,分流比10∶1,进样体积1.0μL,以甲醇为溶解介质.结果 DMF与溶剂峰的分离度良好,其浓度与峰面积呈良好的线性关系,精密度良好,DMF的RSD=1.5％(n=6),回收率为99.8％～100.9％.结论 所用方法适用于比沙可啶原料药中DMF残留溶剂的测定.     

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.     

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.     

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.