HPLC-MS法测定人血浆中的阿立哌唑

目的:建立HPLC-MS法测定人血浆中阿立哌唑浓度的方法。方法:以盐酸洛哌丁胺为内标,采用Thermo Hypersil-HyPURITY C18(150 mm×2.1 mm,5μm)色谱柱;以20 mmol.L-1醋酸铵溶液(0.7%乙酸,0.1%TFA)-甲醇-乙腈(37∶50∶13)为流动相;柱温:40℃;流速:0.3 mL.min-1。结果:标准曲线线性范围为1.0~200ng.mL-1;萃取回收率为72.03%~74.35%;方法回收率为97.00%~100.80%;日内RSD在5.74%~10.69%;日间RSD在5.87%~11.26%。结论:本方法快速、灵敏、准确、简便,适用于阿立哌唑血药浓度测定及药动学研究。     

精神分裂症患者阿立哌唑血药浓度检测的相关性研究

目的建立测定精神分裂症患者血浆阿立哌唑药物浓度的反相高效液相色谱(RP-HPLC)法。方法选用C18色谱柱,检测波长257 nm,流动相为乙腈-甲醇(40.5∶59.5),乙醚+二氯甲烷为提取剂,流速1 ml/min。测定34例单一服用阿立哌唑的精神分裂症患者的血药浓度。结果阿立哌唑日内和日间精密度(RSD)分别<3.6%和<3.5%,平均回收率97.43%,最低有效检测浓度为5 ng/ml,阿立哌唑在5～800 ng/ml内有良好的线性关系,患者口服阿立哌唑日剂量20～30 mg测得阿立哌唑的平均血药浓度为(371.2±36.6)ng/ml。结论本方法操作简便、灵敏度高、准确性好,可用于临床监测阿立哌唑血药浓度和药代动力学研究。     

反相高效液相色谱法测定阿立哌唑血药浓度

目的:建立阿立哌唑血药浓度的测定方法.方法:反相高效液相色谱法,采用Kromasil C18柱(5 μm,4.6 mm×250 mm);流动相为甲醇-0.02 mol·L-1醋酸铵-三乙醇胺(92∶8∶1,氨水调pH 9.9);流量:1.0 mL·min-1;检测波长 254 nm. 结果:阿立派唑的线性范围为100～800 ng·mL-1,r=0.997 6,平均加样回收率99.05%.结论:本法操作简便、准确,可以应用于临床监测阿立哌唑血药浓度.     

高效液相色谱法测定人血浆中阿立哌唑浓度

目的:建立以高效液相色谱法测定人血浆中阿立哌唑浓度的方法。方法:血浆样品经液-液提取后,采用高效液相色谱法检测。色谱柱为C18,流动相为0．03mol·L-1醋酸铵-乙腈(34:66),流速为0．8mL·min-1,柱温为40℃,检测波长为257nm,灵敏度为0．01 AUFS。结果:阿立哌唑检测浓度线性范围为5．0～600．0ng·mL-1(r=0．999 5),提取回收率均大于90％。结论:该方法灵敏、准确、快速,适用于人血浆中阿立哌唑浓度的检测。     

HPLC-MS/MS法研究阿立哌唑不同晶型的药动学差异

目的 研究阿立哌唑不同晶型的药动学特性,为寻找其优势晶型奠定基础。方法 大鼠单次灌胃给予阿立哌唑的4种不同晶型(晶型α、晶型Ⅳ、倍半水合物和新晶型)各2 mg·kg^-1,用高效液相色谱-串联质谱法(HPLC-MS/MS法)测定血浆中阿立哌唑及其代谢物脱氢阿立哌唑的质量浓度,分析不同晶型的药代动力学差异。血浆样品处理用醋酸乙酯液-液萃取法,以替米沙坦为内标物。色谱柱：Thermo-C₁₈(100 mm×4.6 mm, 1.7μm);流动相：甲醇-50 mmol·L^-1甲酸铵(10∶90);流速：0.2 mL·min^-1;柱温：40℃。质谱用电喷雾离子源(electrospray ionization, ESI)、正离子电离模式为多反应监测(multiple reaction monitoring, MRM)的质谱扫描方式测定(m/z):阿立哌唑448.0→285.1;脱氢阿立哌唑446.1→285.1;替米沙坦515.1→497.3。结果 大鼠分别单剂量灌胃给予阿立哌唑的4种晶型后,不同晶型的药代动力...     

阿立哌唑片溶出度测定

目的:建立了阿立哌唑片的溶出度测定方法.方法:采用中国药典方法,以醋酸溶液(6→1000)(0.1 mol·L-1)作为溶出递质,转速为50 r·min-1,用紫外分光光度法在257 nm处测定阿立哌唑的溶出量,45 min时溶出限度为标示量的75%.结果:阿立哌唑在5.10～30.63 mg·L-1范围内线性关系良好(r=0.999 5),平均回收率99.8%.结论:该法准确,快速,简便.     

顶空气相色谱法测定阿立哌唑中有机溶剂N,N-二甲基甲酰胺残留量

目的:建立测定阿立哌唑原料药中的有机溶剂N,N-二甲基甲酰胺(DMF)残留量的方法.方法:采用顶空气相色谱法,DB-624毛细管柱(30m×0.53mm,3μm),载气为氮气,流速20mL·min-1,柱温90℃;气化室温度160℃;氢火焰离子化检测器(FID)温度170℃.结果:在浓度范围9.32～1.19×103μg·mL-1内,线性关系良好,r=0.999 9,平均回收率为98.4%.最小检测浓度为4.7μg·mL-1.结论:本方法灵敏,精确,可靠,适用于测定阿立哌唑原料药中的有机溶剂DMF残留量.     

反相高效液相色谱法测定阿立哌唑的有关物质

目的建立测定阿立哌唑有关物质的反相高效液相色谱（RP-HPLC）法。方法色谱柱为Hypersil BDS C18柱（250mm×4.6mm,5μm）,以甲醇-四氢呋喃-以醋酸调pH至3.0的30mmol/L醋酸钠缓冲液（35：25：40）为流动相,流速为1.0mL/min,检测波长为254nm,柱温为35℃。结果阿立哌唑与合成反应中的3个中间体能够得到有效分离,总杂质不超过0.5%,检测限为0.202ng。结论 RP-HPLC法简单、快速、准确、专属,可用于阿立哌唑有关物质的测定。     

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.     

RP-HPLC测定人血浆中阿立哌唑的浓度

目的 建立测定人血浆中阿立哌唑浓度的反相高效液相色谱法.方法 以美国迪马公司钻石C18反相柱(150 mm×4.6 mm, 5 μm)为色谱柱,流动相0.03 mol/L醋酸铵-乙腈(34:66);流速:0.8 ml/min;柱温:40 ℃; 检测波长: 257 nm.以乙酸乙酯与二氯甲烷(80:20)为提取剂.结果 阿立哌唑的高、中、低(600.0, 200.0,10.0 μg/L)3种浓度平均回收率分别为100.43%, 99.33%,99.17%,日内、日间差RSD均低于6%(n=5); 分析方法的最低检测浓度为5.0 μg/L;线性范围为5.0～600.0 μg/L.回归方程为:C=399.42F+3.54,r=0.9996(n=9).结论 该方法灵敏、准确、简单、快速,可用于临床血药浓度监测和药动学研究.     

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.     

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.     

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.     

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.