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。     

毛细管气相色谱法测定瑞舒伐他汀钙中有机溶剂残留量

目的:建立毛细管气相色谱法测定瑞舒伐他汀钙中有机溶剂的残留量.方法:采用HP-FFAP毛细管色谱柱,载气为氮气,流速为6 ml·min-1;分流比为5:1;程序升温;氢火焰离子化检测器(FID),检测器温度250℃,进样口温度200℃;按外标法测定溶剂残留量.结果:乙醇、乙酸乙酯、四氢呋喃和甲苯分别在100.58～1 005.80(r=0.999 9)、102.00～1 020.00(r=0.999 9)、14.66～146.60(r=0.999 9)、19.12～191.20 μg·m1-1(r=0.999 9)范围内,线性关系良好;平均回收率分别为99.1%(RSD=2.0%),98.5%(RSD=1.6%),98.9%(RSD=1.8%),99.2%(RSD=2.1%).结论:该方法专属性好、快速、简单、结果准确,可用于瑞舒伐他汀钙中有机溶剂残留量的测定.     

毛细管气相色谱法同时测定盐酸替利定原料药中4种有机溶剂残留量

目的:建立了以毛细管气相色谱法同时测定盐酸替利定原料药中丙酮、乙酸乙酯、四氢呋喃、甲苯4种有机溶剂残留量的方法。方法:色谱条件为DB-1701毛细管柱,氢火焰离子化检测器,检测器温度为250℃,柱温采用程序升温,初始温度为35℃,保持8min,以30℃·min-1升至180℃,保持2min,进样口温度为155℃,载气为氮气,流速为0.7mL·min-1,分流比为15∶1,进样量为1μL;以二甲基甲酰胺为溶剂。结果:丙酮、乙酸乙酯、四氢呋喃、甲苯的检测浓度线性范围分别为0.100～1.000、0.100～1.000、0.018～0.144、0.0178～0.178mg·mL-1(r为0.9993～0.9999),平均加样回收率为98.2%～99.5%,RSD小于1.5%。3批样品中乙酸乙酯均未检出,丙酮、四氢呋喃、甲苯残留量均符合《中国药典》2005年版要求。结论:本法快速、灵敏、准确,适用于盐酸替利定原料药中有机溶剂残留量的测定。     

顶空气相色谱法测定洛伐他汀原料药中的有机溶剂残留量

目的:建立测定洛伐他汀原料药中乙醇、丙酮、乙酸乙酯、甲苯4种有机溶剂残留量的方法。方法:采用顶空气相色谱法。色谱柱为DB-624石英毛细管柱,柱温采用程序升温,检测器为氢火焰离子化检测器,检测器温度为280℃,进样口温度为160℃。结果:乙醇、丙酮、乙酸乙酯、甲苯的检测浓度的线性范围分别为10.0～250(r=1.0000)、10.0～250(r=0.9999)、10.0～250(r=0.9999)、1.78～89μg.mL-(1r=0.9997);平均回收率为97.6～99.1(RSD=0.9～1.9),定量限为0.22～5.61μg.mL-1;4批样品中4种有机溶剂残留量均符合《中国药典》2005年版要求。结论:该方法操作简便、精密度好,结果准确、可靠。     

GC同时测定麝香通心滴丸中龙脑、异龙脑和麝香酮的含量

摘要：目的 建立同时测定麝香通心滴丸中龙脑、异龙脑及麝香酮含量的气相色谱法。方法 色谱柱：HP-5MS毛细管色谱柱(30 m×0.32 mm,0.25 μm),检测器为FID检测器,检测器温度为250 ℃,进样口温度220 ℃。柱温以100 ℃为初始温度,保持2分钟,以2 ℃?min-1升温至110 ℃,保持3分钟,以50 ℃?min-1升温至205 ℃,保持7分钟,以20 ℃?min-1升温至250 ℃,保持2分钟;载气为氮气,流速为1 mL?min-1;进样方式为分流进样,分流比为10：1;进样量为1 μL,以萘为内标。结果 龙脑、异龙脑、麝香酮的浓度分别在0.05468~0.4374 mg?mL-1(r=0.9999),0.07067~0.5654 mg?mL-1(r=0.9999),0.004512~0.03610 mg?mL-1(r=0.9997)的范围内线性良好;平均回收率分别为97.91 %(RSD=2.05 %),100.79 %(RSD= 2.78 %),105.36 %(RSD=3.78 %)。结论 该方法有效可靠,可用于麝香通心滴丸中龙脑、异龙脑和麝香酮的含量测定。     

毛细管气相色谱法检测普伐他汀中有机溶剂的残留量

目的:建立以毛细管气相色谱法检测普伐他汀原料药中有机溶剂残留量的方法。方法:检测器为氢火焰离子化检测器(FID),色谱柱为DB-5毛细管色谱柱,初始柱温为40℃,保持3min后以40℃.min-1升至180℃,保持3min,进样口温度为200℃,检测器温度为240℃,进样量为0.3μL,检测对象为9种溶剂,包括甲醇、乙腈、二氯甲烷、正己烷、三氯甲烷、四氢呋喃、乙酸乙酯、甲苯、N,N-二甲基甲酰胺。结果:9种有机溶剂实现基线分离,线性关系良好(r均大于0.998 9),平均回收率为98.5%～100.8%,RSD=2.0%～4.2%,最低检测浓度为0.10～1.38ng.mL-1,均未在普伐他汀原料药中检出。结论:本方法操作简便、结果准确,可用于普伐他汀原料药中有机溶剂残留量的测定。     

毛细管气相色谱法同时测定卡格列净原料药中甲醇等6种有机溶剂残留量

目的建立直接进样气相色谱法测定卡格列净中甲醇、乙腈、乙酸乙酯、甲苯、四氢呋喃和正庚烷共6种有机溶剂的残留量。方法采用毛细管气相色谱法测定,毛细管色谱柱为CP-SIL 8CB(25 m×0.53 mm,5.0μm)柱,采用FID检测器,以氮气为载气,流速为3.0 m L·min-1,采用程序升温,初始柱温为40℃,保持6 min,以30℃·min-1升至160℃,保持2 min,再以30℃·min-1升至200℃,保持3 min,进样口温度为160℃,检测器温度为250℃,溶液直接进样,分流比为20∶1,用内标法计算6种溶剂的残留量。结果在本色谱条件下6种残留溶剂在各自浓度范围内均具有良好的线性关系,平均回收率为98.8%~107.4%(n=9),RSD为0.7%~3.9%(n=9),重复性RSD≤2.5%(n=6)。结论本方法适用于同时测定卡格列净中甲醇、乙腈、乙酸乙酯、甲苯、四氢呋喃和正庚烷共6种有机溶剂残留量。     

顶空毛细管气相色谱法测定替卡西林钠原料药中的有机溶剂残留量

目的:建立测定替卡西林钠原料药中甲醇、乙醇、丙酮、二氯甲烷、乙酸乙酯、甲苯6种有机溶剂残留量的方法。方法:采用顶空气相色谱法。色谱柱为DB-624石英毛细管柱,柱温采用程序升温,检测器为氢火焰离子化检测器,检测器温度为250℃,进样口温度为150℃,以水为溶解介质。结果:甲醇、乙醇、丙酮、二氯甲烷、乙酸乙酯、甲苯的检测浓度的线性范围分别为12.0～1200(r=0.9999)、10.0～1000(r=0.9998)、10.0～1000(r=0.9999)、1.20～120(r=0.9997)、10.0～1000(r=0.9998)、1.78～178μg·mL-1(r=0.9996);平均回收率为98.5%～99.6%(RSD=0.6%～2.0%);定量限为0.20～11.80μg·mL-1;3批样品中6种有机溶剂残留量均符合《中国药典》要求。结论:本方法简单、准确、灵敏度高、重复性好,可用于该原料药中有机溶剂残留量的测定。     

毛细管气相色谱法测定盐酸莫西沙星中有机溶剂的残留量

目的 采用毛细管气相色谱法测定盐酸莫西沙星原料药中6种有机溶剂的残留量.方法 采用毛细管气相色谱法,DB-624色谱柱,程序升温,以二甲基亚砜为溶剂,进样口温度为200℃,FID检测器温度为250℃,载气流速为2.0mL·min-1,对甲醇、丙酮、乙腈、二氯甲烷、四氢呋喃和三乙胺的残留量进行检测.结果 6种有机溶剂基本实现基线分离且线性关系良好(r均在0.9990以上);甲醇、丙酮、乙腈、二氯甲烷、四氢呋喃和三乙胺的检测限分别为0.98,0.81,0.50,2.14,0.40,0.61μg·mL-1;平均回收率为92.06％～ 99.77％,RSD为1.6％～3.0％(n=9).结论 该法适用于盐酸莫西沙星中这6种有机溶剂残留量的测定.     

顶空毛细管气相色谱法测定盐酸莫雷西嗪中残留溶剂的含量

目的建立顶空气相色谱法测定盐酸莫雷西嗪中甲醇、乙醇、异丙醇、二氯甲烷、乙酸乙酯、四氢呋喃、甲苯7种有机溶剂残留量的方法。方法色谱柱为DB-624石英毛细管柱,柱温采用程序升温,检测器为FID检测器,检测器温度为250℃,进样口温度为150℃,以水为溶解介质。结果甲醇、乙醇、异丙醇、二氯甲烷、乙酸乙酯、四氢呋喃、甲苯的质量浓度的线性范围分别为12.0~240 mg.L-1(r=1.000 0)、10.0~200 mg.L-1(r=0.999 9)、10.0~200 mg.L-1(r=0.999 9)、1.20~24 mg.L-1(r=0.999 9)、10.0~200 mg.L-1(r=0.999 9)、1.44~28.8 mg.L-1(r=0.999 8)、1.78~35.6 mg.L-1(r=0.999 7);平均回收率为98.1%~99.5%(RSD=0.6%~1.7%);定量限为0.22~11.91 mg.L-1;3批样品中7种有机溶剂残留量均符合《中华人民共和国药典》要求。结论本方法简单、准确、灵敏度高、重现性好,可用于该药物中有机溶剂残留量的测定。     

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.     

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.     

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.