艾拉莫德原料药中残留溶剂检测方法的研究

目的:检查艾拉莫德原料药中的有机溶剂残留量。方法:采用气相色谱法测定,色谱柱为HP-5弹性石英毛细管柱(以5％苯基-95％甲基聚硅氧烷为固定液,1.5μm,30 m×0.53 mm);进样口温度:200℃;氢火焰离子化检测器(FID),检测器温度:300℃;柱温:程序升温,初始温度30℃,保持13 min,以5℃·min-1升温至35℃,保持7 min,再以10℃·min-1升温至230℃,保持5 min;载气:氮气;流速:1.5 mL·min-1;以N-甲基吡咯烷酮为溶剂,正丙醇为内标物。结果:被测物均能得到很好的分离,峰面积与浓度呈良好的线性关系,精密度良好。结论:该法可用于艾拉莫德原料药中有机溶剂残留量检测。     

毛细管气相色谱法测定盐酸头孢唑兰有机溶剂残留量

目的 建立毛细管气相色谱法测定盐酸头孢唑兰有机溶剂残留量。方法 色谱柱：采用气相色谱法测定,聚乙二醇为固定相的毛细管色谱柱(WAX 30.0m×0.53mm,1.0μm)(30.0m×0.53mm,1.0um);载气为氮气。检测器温度：250℃;进样口温度：200℃;程序升温：初始温度50保持6min,以15℃.min-1升温至180℃,保持5 min;顶空进样。平衡温度为70℃,平衡时间为30 min。分流比为1：5,溶剂为二甲基亚砜。结果 被测物均能得到很好的分离,峰面积与浓度呈良好的线性关系,精密度良好。结论 该方法可用于盐酸头孢唑兰中有机溶剂残留量的检测。     

顶空气相色谱法测定托拉塞米原料药中残留溶剂

目的:检查托拉塞米原料药中甲醇、二氯甲烷、甲苯、二氧六环等有机溶剂残留量。方法:采用气相色谱(GC)法测定,色谱柱为HP-5弹性石英毛细管柱(5%-苯基甲基聚硅氧烷为固定液,30 m×0.53 mm,1μm),进样口温度220℃;氢火焰离子化检测器(FID)温度:240℃;柱温:程序升温,初始温度40℃,保持10 min,以40℃·min-1升温至200℃,保持3 min;载气:N2;流速:5 mL·min-1;以二甲亚砜为溶剂,丙酮为内标物。结果:被测物均能得到很好的分离,峰面积与浓度呈良好的线性关系,精密度良好。结论:该法可用于托拉塞米原料药中有机溶剂残留量检测。     

毛细管气相色谱法测定枸橼酸他莫昔芬原料药中有机溶剂的残留量

目的：建立毛细管气相色谱法测定枸橼酸他莫昔芬原料药中有机溶剂残留量的方法。方法：色谱柱：DB-624（30m×0．53mm×3μm）弹性石英毛细管柱；柱温采用程序升温：起始40℃，保持13min，20℃／min升至230℃，保持15min；氢火焰离子化检测器，载气：氮气，流速：3．0ml·min-1，进样口温度：140℃；检测器温度：250℃；分流比为5：1。结果：甲醇、丙酮、乙酸乙酯、四氢呋喃及甲苯浓度的线性均在各自浓度范围内，线性关系良好。平均回收率为：95．1％～98．1％。结论：方法操作简便、结果准确可靠，可以用于枸橼酸他莫昔芬原料药中有机溶剂残留的测定。     

GC法检测氯法拉滨中有机溶剂的残留量

目的:建立以气相色谱法检测氯法拉滨原料药中7种有机溶剂残留量的方法。方法:毛细管柱为AT-1301;载气为氮气;检测器为火焰离子化检测器;柱温采取程序升温,初始温度40℃,以7℃.min-1升至80℃,再以20℃.min-1升至200℃,保持2min;进样口温度250℃;检测器温度280℃;分流直接进样。检测3批氯法拉滨原料药中甲醇、乙腈、二氯甲烷、叔丁醇、乙酸乙酯、正庚烷、乙酸的残留量。结果:各有机溶剂均能得到有效分离,在所考察的浓度范围内线性关系良好(r=0.99941～0.99993),平均回收率为96.5%～102.4%,RSD均小于4.0%,3批样品中7种有机溶剂残留量均符合《中国药典》要求。结论:本方法灵敏、准确、可靠,可用于氯法拉滨原料药中有机溶剂残留量的检测。     

HS-GC法测定枸地氯雷他定原料药中12种有机溶剂的残留量

目的:建立同时测定不同合成工艺的枸地氯雷他定原料药中12种有机溶剂残留量的方法.方法:采用顶空气相色谱(HS-GC)法.色谱柱为Agilent DB-624(30 m×0.25mm,1.4μm)毛细管柱,程序升温,进样口温度为250℃,检测器为氢火焰离子化检测器,检测器温度为300℃,载气为高纯氮气,载气流速为1.0 ...     

GC法测定羟苯丙酯中8种有机溶剂的残留量

摘要：目的:建立同时测定羟苯丙酯中甲醇、乙醇、正丙醇、异丙醇、正丁醇、异丁醇、仲丁醇和叔丁醇8种有机溶剂残留量的方法。方法:采用DB-624毛细管柱（0.32 m×30 mm,1.8μm）; FID检测器;进样口温度为200℃,检测器温度为250℃;载气为高纯氮气,载气流速为2.0ml·min-1;柱温为升温程序,起始温度45℃,保持2min,以5℃·min-1升温至65℃保持5 min,再以40℃·min-1升温至200℃保持3 min。结果:羟苯丙酯中8种残留溶剂在各自浓度范围内线性关系良好（r均>0.999）;平均回收率为102.1%～106.2%。结论:本方法操作简单、准确度高、重复性好,可用于羟苯丙酯中8种有机溶剂残留量的测定。     

GC法测定盐酸司他斯汀中2-氯乙醇基因毒性杂质

摘要：目的:建立气相色谱法测定盐酸司他斯汀中2-氯乙醇的残留量。方法:采用HP-5（60 m×0.320 mm,1.00μm）毛细管柱;以微池电子捕获检测器（u ECD）为检测器,温度为280℃;进样口温度为220℃;柱温:程序升温,起始温度为40℃,维持13 min,以50℃·min-1的速率升温至310℃,维持10 min;载气为氮气,流速为4.0 ml·min-1;分流比:3∶1,进样量为1μl。结果:2-氯乙醇在2.038～13.250μg·ml-1浓度范围内,线性关系良好（r=0.997 8）,平均回收率为85.90%,RSD=2.41%（n=9）,定量限为1.019μg·ml-1（0.002 5%）,检测限为0.510μg·ml-1（0.001 3%）。结论:本测定方法操作简便、准确、经济,可用于盐酸司他斯汀原料药中2-氯乙醇残留量的日常检测。     

气相色谱法测定他米巴罗汀原料药中4种有机溶剂残留量

目的建立他米巴罗汀原料药中4种有机溶剂残留量的分离测定方法。方法采用毛细管气相色谱法,色谱柱为DB-624石英毛细柱(30m×0.53mm×1.0μm),FID检测器,载气为高纯氮气,柱温为程序升温,测定了他米巴罗汀原料药中甲醇、二氯甲烷、正己烷和乙酸乙酯的残留量。结果 4种有机溶剂完全分离,在所考察范围内线性关系良好,加样回收率均得到满意结果。结论建立的方法灵敏、准确,适用于他米巴罗汀原料药中有机溶剂残留量的检测。     

顶空气相色谱法测定盐酸吉西他滨中的残留溶剂

目的：测定盐酸吉西他滨原料药中的有机溶剂残留量。方法：采用项空气相色谱法,DB击24石英毛细管柱（30m×0．53mm,3μm）,汽化室温度250℃;氢火焰离子化检测器（FID）温度：300℃;柱温：程序升温,起始柱温为40℃,保持6min,以10％·min^-1升温至120℃。以40℃·min^-1升温至230℃保持10min;载气：氮气。结果：被测物质均能得到很好的分离,峰面积与浓度呈良好的线性关系。结论：该法可以作为盐酸吉西他滨原料药中有机溶剂残留量的检测。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.     

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.