高效液相色谱法测定盐酸特拉唑嗪渗透泵控释片的含量

目的:建立盐酸特拉唑嗪渗透泵控释片的含量测定方法。方法:采用高效液相色谱法,色谱柱为ODS C18柱(150mm×4.6mm,5μm);流动相为甲醇-水-冰醋酸-二乙胺(35∶65∶1?0.02);检测波长:246nm。结果:盐酸特拉唑嗪在10.00~60.00mg.L-1之间,线性关系良好,r=0.999 5(n=6),平均回收率为99.67%,RSD为0.12%。结论:高效液相色谱法测定盐酸特拉唑嗪渗透泵控释片含量,无内源性物质的干扰,专属性强、灵敏度高,为该药质量控制提供参考依据。     

HPLC加校正因子的主成分自身对照法测定盐酸特拉唑嗪片中有关物质的含量

目的:建立测定盐酸特拉唑嗪片中有关物质含量的方法。方法:采用高效液相色谱加校正因子的主成分自身对照法。色谱柱为Agilent Zorbax Eclipse XDB C18,流动相为乙腈-高氯酸溶液(20∶80,V/V),流速为1.0 mL/min,检测波长为246 nm,进样量为20μL,柱温为50℃;绘制盐酸特拉唑嗪和杂质A、B、C的线性方程,以斜率计算各杂质相对于盐酸特拉唑嗪的校正因子,用相对保留时间确定各杂质位置,测定3批盐酸特拉唑嗪片中杂质A、B、C的含量,并与杂质对照品法测得的结果进行比较。结果:盐酸特拉唑嗪杂质A、B、C的相对保留时间分别为0.39、0.74、2.77,检测质量浓度线性范围均为0.25～3.0μg/mL,校正因子分别为0.75、1.09、0.84,检测限分别为0.35、0.51、0.43 ng,定量限分别为0.70、1.02、0.86 ng。3批盐酸特拉唑嗪片中杂质A、B、C的含量分别为0.11%～0.13%、0.03%、0.09%～0.12%,杂质B未检出;与杂质对照品法测定结果一致。结论:该方法简便快速,可准确测定盐酸特拉唑嗪片中有关物质的含量。     

HPLC 法测定盐酸特拉唑嗪胶囊的含量和有关物质

目的:建立了HPLC 法测定盐酸特拉唑嗪胶囊的含量及有关物质.方法:色谱柱为Thermo C18柱(250×4.6mm,5μm),流动相:乙腈-三乙胺高氯酸溶液(取三乙胺2ml,置1000ml水中,用高氯酸调节pH2.0)(20:80),检测波长246nm,流速:1.0mL·min-1,柱温:40℃.结果:盐酸特拉唑嗪...     

反相高效液相色谱法测定人血浆中特拉唑嗪片的血药浓度

目的建立测定人血浆中特拉唑嗪片浓度的高效液相色谱法。方法采用Kromail C18色谱柱(4.6 mm×250 mm,5μm),以乙腈-四氢呋喃-0.01 mol/L磷酸二氢钾(15∶5∶80)为流动相,检测波长为254 nm。结果盐酸特拉唑嗪线性范围:10.0~400.0 ng/mL,最低定量限:10.0 ng/mL,回归方程L:Y=45.01X+483.67,r=0.990 3(权重1/c2×106)。结论该方法简便、快速、准确,适于盐酸特拉唑嗪临床药物动力学研究。     

高效液相色谱法测定盐酸特拉唑嗪及其胶囊中的有关物质

目的:建立高效液相色谱法测定盐酸特拉唑嗪及其胶囊剂中的有关物质.方法:采用色谱柱:DiamonsilC18色谱柱(150mm×4.6mm 5um);流动相:甲醇-水-冰醋酸-三乙胺(330:670:10:0.3);检测波长:246nm;流速:1.0ml·min-1.结果:原料药可检测出5个杂质峰,胶囊剂可检测出6个杂质峰.结论:本法简便,准确,灵敏度高,可用于盐酸特拉唑嗪及其胶囊剂中中有关物质的测定.     

反相高效液相色谱法和薄层色谱法检查左羟丙哌嗪的有关物质

目的建立2种检测方法对左羟丙哌嗪的有关物质进行检测.方法反相高效液相色谱法色谱柱为Hypersil-ODS2(200mm×4.6mm,10μm),流动相为甲醇-0.05mol@L-1磷酸二氢钾溶液(3070),用磷酸调pH3.0;检测波长为242nm.薄层色谱法以硅胶G为吸附剂,乙酸乙酯-乙醇-氯仿-浓氨水(15880.5)为展开剂,碘蒸气显色.结果反相HPLC法左羟丙哌嗪与苯基哌嗪的tR值分别为5.7与8.5min;最低检出限量为0.1μg@mL-1.TLC法左羟丙哌嗪与苯基哌嗪的Rf值分别为0.62与0.46;最低检出限量为15μg@mL-1.结论2种方法均可用于左羟丙哌嗪有关物质的检查.反相HPLC法灵敏度高,检出限量低;TLC法方便、快速.     

HPLC法测定盐酸阿夫唑嗪片中盐酸阿夫唑嗪的含量

目的　建立用HPLC法测定盐酸阿夫唑嗪片中盐酸阿夫唑嗪含量。方法　以盐酸特拉唑嗪为内标,采用Alltima-CN柱,流动相为 0 0 5mol·L-1磷酸二氢钠溶液(0 5mol·L-1的氢氧化钠溶液调pH至 5 4 ) -乙腈(78∶2 2);检测波长:2 4 4nm。结果与结论　盐酸阿夫唑嗪在 5～ 5 0 μg·ml-1范围内呈良好的线性关系,回收率为 99 8%,RSD =0 9% (n =9)。     

HPLC测定盐酸普拉克索缓释片中的有关物质

目的采用HPLC法测定盐酸普拉克索缓释片中的有关物质。方法采用Waters Sunfire C18色谱柱,以0.1 mol·L-1乙酸铵(p H5.0,含0.1%三乙胺)-甲醇(98∶2)为流动相A,以甲醇为流动相B,梯度洗脱,检测波长264、326 nm,柱温40℃,流速1.0 m L·min-1。结果高、中、低浓度杂质的平均回收率为90.5%~105.8%(n=9);最低检出限为0.15~0.60 ng。结论所用方法简便、快速、灵敏,可用于检测盐酸普拉克索缓释片中的有关物质。     

高效液相色谱法测定依托度酸缓释片中的有关物质

目的:建立以高效液相色谱法测定依托度酸缓释片中有关物质的方法。方法:色谱柱为C18,流动相为甲醇-乙腈-0.055mol/L醋酸铵溶液(60∶40∶900)与甲醇-乙腈-0.5mol/L醋酸铵溶液(540∶360∶100),并进行梯度洗脱,流速为1.0ml/min,柱温为35℃,检测波长为220nm,进样量为10μl。结果:各项专属性试验中,依托度酸主峰与其它杂质峰均分离较好;3批样品中各杂质的检测均符合依托度酸缓释片中有关物质检查的要求。结论:本方法可用于依托度酸缓释片中有关物质的检测。     

反相高效液相色谱法测定盐酸阿夫唑嗪片的含量

目的:建立盐酸阿夫唑嗪片含量测定的反相高效液相色谱法.方法:采用PhenomenexR LUNA C18(2) (250mm×4.6mm,5μm)色谱柱,以甲醇-水-冰乙酸-三乙胺(590∶360∶60∶5.0)为流动相,流速0.8mL·min-1,检测波长244nm,柱温为室温,进样10μL.考察了流动相不同配比、不同pH对盐酸阿夫唑嗪片色谱行为的影响.结果:盐酸阿夫唑嗪与片剂辅料及其他杂质可完全分离;在10～200μg·mL-1浓度范围内线性关系良好(r=0.999 9),平均回收率99.68%,RSD=0.78%.结论:该方法操作简便,结果准确,专属性强,可用于盐酸阿夫唑嗪片的含量测定.     

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.     

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.