顶空进样气相色谱法测定氟伐他汀钠中残留溶剂

目的建立顶空进样气相色谱法检测氟伐他汀钠原料药中7种残留溶剂。方法采用顶空进样气相色谱法。色谱柱为CP-sil 5CB毛细管柱(60 m×0.32 mm,5μm);进样口温度:180℃;氢火焰离子化检测器温度:250℃;柱温:120℃;载气:氮气;流速:1.2 m L·min-1;分流比2∶1。顶空进样,顶空平衡温度80℃,顶空平衡时间30 min,进样体积1.0 m L。结果各被测溶剂均能良好分离,各溶剂峰面积与浓度均呈良好的线性关系,方法的精密度良好,回收率均较为理想。结论该方法适用于氟伐他汀钠原料药的残留溶剂测定。     

顶空气相色谱法测定福沙匹坦二甲葡胺中8种残留溶剂的含量

目的:建立顶空气相色谱法测定福沙匹坦二甲葡胺中甲醇、乙醇、丙酮、乙腈、甲基叔丁基醚、四氢呋喃、乙酸乙酯及甲苯残留量的方法。方法:采用顶空气相色谱法,色谱柱为DB-624毛细管柱(30 m×0.53 mm,3.0μm),载气为氮气,流速为2.0 ml·min^-1,进样口温度为200℃,FID检测器,检测器温度为250℃,程序升温:起始温度为45℃,维持5 min,再以20℃·min^-1的速率升温至200℃,维持3 min。顶空平衡温度为80℃,平衡时间为20 min。结果:8种残留溶剂分离度良好,在一定浓度范围内呈良好的线性关系(r≥0.9997),平均回收率在95%~105%范围内,检出限分别为0.19,0.31,0.06,0.13,0.03,0.05,0.16,0.12μg·ml^-1。结论:该方法灵敏度高,准确度好,适用于福沙匹坦二甲葡胺原料药中残留溶剂的测定。     

GC测定拉科酰胺原料药中的5种残留溶剂

目的建立顶空进样气相色谱法检测拉科酰胺原料药中5种残留溶剂的方法。方法采用顶空毛细管气相色谱法,色谱柱为AgilentHP-5石英毛细管柱（30．0m×0．32mm×0．25μm）;进样口温度：210℃;FID检测器温度：240℃;柱温：50℃;载气：氮气;流速：1．0mL·min^-1。顶空进样,顶空平衡温度：85℃,顶空平衡时间：30min;进样体积：0．35mL。结果在上述条件下,5种残留溶剂均能良好分离,各溶剂峰面积与浓度均呈良好的线性关系,方法精密度良好,回收率均较为理想。结论该法适用于拉科酰胺原料药中残留溶剂的测定。     

顶空毛细管气相色谱法测定奥硝唑原料的溶剂残留

目的建立奥硝唑原料药中5种有机溶剂残留量的顶空毛细管气相色谱测定法。方法使用Agilent DB-624毛细管气相色谱柱(30m×0.32mm×0.18μm),FID检测器,进样口温度150℃,检测器温度250℃。程序升温45℃,保持15min,然后以40℃·min-1的速率升至220℃。顶空进样,平衡温度85℃,平衡时间30min。结果在上述条件下,甲醇,乙醇,乙酸乙酯,二氯乙烷和环氧氯丙烷的分离度均在2.0以上,线性关系良好(r在0.997 8~0.999 9之间),平均回收率(n=6)在100.9%~103.4%之间,RSD在1.4%~3.3%之间。结论该法简单、准确,可用于奥硝唑原料中残留溶剂的测定。     

顶空毛细管气相色谱法测定乌拉地尔原料药的溶剂残留量

目的:建立乌拉地尔原料药中5种溶剂残留量的毛细管气相色谱测定方法。方法:采用Agilent DB-5毛细管气相色谱柱(30m×320μm×0.25μm),FID检测器,进样口温度200℃,检测器温度230℃;载气为高纯氮气,流速3.0mL.min-1,柱温为程序升温:40℃保持10min,10℃.min-1升温至220℃,保持5min。顶空进样,顶空瓶平衡温度80℃,平衡时间30min。结果:在上述条件下,5种残留溶剂色谱峰的理论板数均大于10 000,相邻峰的分离度均大于2;甲醇、乙醇、丙酮、二氯甲烷、1,2-二氯乙烷的线性关系良好(r分别为0.999 2,0.999 3,0.999 9,0.999 8和0.999 8);最低检出浓度分别为:0.46,0.46,0.23,0.31,0.090μg.mL-1;平均回收率均在90%以上。结论:本方法简单、准确,灵敏度高、重复性好,适用于乌拉地尔原料药中有机溶剂残留量的测定。     

顶空气相色谱法测定恩格列净原料药中10种溶剂的残留量

目的建立顶空进样气相色谱法测定恩格列净原料药中10种溶剂的残留量,以期为恩格列净原料药的质量控制提供试验依据。方法采用顶空气相色谱法测定;毛细管色谱柱为Aglient DB-624柱(25 m×0.53 mm,3.0μm);程序升温;FID检测器;氮气为载气;流速为1.0 m L·min-1;顶空平衡温度为80℃;平衡时间为20 min;用外标法计算甲醇、乙腈、二氯甲烷、环己烷、四氢呋喃、乙醇、乙醚、叔丁基甲醚、乙酸乙酯和乙酸共10种残留溶剂的含量。结果在本色谱条件下10种残留溶剂在各自的质量浓度范围内均具有良好的线性关系,平均回收率为90.45%~102.45%,重复性RSD≤2%(n=6)。结论本方法适用于恩格列净原料药中溶剂残留量的检查。     

毛细管气相色谱法测定奥沙利铂原料药中有机溶剂的残留量

目的建立以毛细管气相色谱法检测奥沙利铂原料中2种有机溶剂乙醚、乙醇残留量的方法。方法采用聚乙二醇毛细管柱(30.0m×530μm×3μm);氢火焰离子化检测器(FID);柱温采用程序升温:初温60℃(保持4min),以30℃/min升温至180℃(保持5min);载气为N2;进样口温度:220℃;检测器温度:250℃;丙酮为内标进行测定。结果奥沙利铂原料药中残留溶剂乙醚和乙醇达到完全分离,且均呈现良好的线性关系和回收率,3批样品检测残留溶剂均未超标。结论本测定方法简单、准确,适用于奥沙利铂原料药中残留溶剂的测定。     

顶空气相色谱法测定硝唑尼特中的残留溶剂

目的:建立项空气相色谱测定药物硝唑尼特中残留溶剂的方法.方法:采用DM-WAX毛细管色谱柱(30 m×0.25 mm,0.5 μm);柱温采取程序升温;进样口温度为200℃;FID检测器,检测器温度为250℃;顶空进样,平衡温度为80℃,平衡时间为30 min;以N,N-二甲基甲酰胺为溶剂测定硝唑尼特原料药中丙酮、二氯甲烷的残留量.结果:在本文的色谱条件下,各有机溶剂均能得到有效分离,丙酮、二氯甲烷的浓度分别在250～750 μg·ml-1(r=0.9991)、30～90 μg· ml-1(r=0.9991)范围内线性关系良好;平均回收率分别为99.15％、99.18％,RSD分别为2.17％、2.97％(n=9).结论:本方法简便、快速、准确,可有效检测硝唑尼特中的残留溶剂.     

气相色谱法测定依普利酮原料药中的残留溶剂

目的:建立依普利酮原料药中残留溶剂:甲醇、乙醇、二氯甲烷和乙醚的限度检测方法.方法:顶空气相色谱法,氢火焰离子化检测器,以水为溶剂,色谱柱为HP-INNOWAX毛细管柱(30 m×0.32 mm×0.5 μm);检测器温度300℃;进样口温度200℃;柱温35℃,保持10 min;流量为1 mLmin-1;载气为高纯氮气.结果:各残留溶剂均能很好的分离,在所考察浓度范围内呈现良好的线性关系(r=0.9988～0.9997),精密度RSD值均小于5%.结论:方法简单、可靠,精确,可用于该原料药残留溶剂量的控制.     

顶空气相色谱法测定麝香草酚中的残留溶剂

目的建立顶空气相色谱法测定麝香草酚中有机残留溶剂异丙醇和正己烷的方法。方法采用顶空气相色谱法,色谱柱为RTX-624(0.53 mm×30 m,3μm);氢火焰离子化检测器(FID),检测器温度为250℃;进样口温度为180℃;顶空平衡温度为80℃,顶空平衡时间为25 min;程序升温:50℃保持6 min,以30℃·min-1的速度升至180℃保持3 min;以N,N-二甲基甲酰胺(DMF)为溶剂。结果在该色谱条件下,异丙醇和正己烷达到完全分离,分别在5.174~77.61μg·m L-1和0.3002~4.503μg·m L-1内,线性关系良好,相关系数分别为0.9985和0.9974,平均回收率均在99%~103.6%(RSD<6.0%,n=3)。2种残留溶剂的残留量均符合中国药典2010年版的规定(异丙醇限度为0.5%,正己烷限度为0.029%)。结论该方法简单、准确、灵敏度、重复性好,可用于麝香草酚中有机残留溶剂的检测。     

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.

---

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.     

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.     

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.