反相高效波相色谱法测定华法令钠血药浓度

建立了反相高效液相色谱测定华法令钠血浆中浓度的方法.方法使用Nova-Pak C_(18)柱;流动相为甲醇:0.001 mol/L醋酸钠溶液=55:45,用冰醋酸调PH 6.0;以卡马西平为内标;提取溶媒为30%异丙醇氯仿;紫外检测波长300nm;流动相流速0.8ml/min.方法最低检出限10ng,最低检出浓度50μg/L.华法令钠血药浓度在0.25～40mg/L范围内线性关系良好(r=0.9999).本方法适用于常规监测华法令钠血药浓度工作.     

氨吡酮血药浓度的测定方法

建立了氨吡酮浓度的HPLC测定方法.本法简便、快速.流动相为甲醇:水:二乙胺=35:65:0.3,流速lml/min,检测波长254nm,氨吡酮和内标的保留时间分别为3.15和5.45min.氨吡酮的最低检测浓度为0.05μg/ml.氨吡酮在浓度0～10μg/ml范围内呈线性关系(r=0.9998),在浓度为0.5,5,10μg/ml时的绝对回收率和相对回收率分别为68.74%,66.64%,66.92%和99.64%,99.13%,99.54%.心力衰竭病人中氨吡酮的血药浓度为1.10～3.21μg/ml.     

柱切换HPLC法测定豚鼠体内诺氟沙星银解离物诺氟沙星的浓度

用柱切换HPLC法建立了豚鼠血浆和皮下组织液中诺氟沙星银体内主要解离物诺氟沙星的测定方法。预处理柱为μ-BondapakC₁₈,37～50μm,50mm×5mmID;分析柱为YWG-C₁₈,10μm,150mm×5mmID。预处理流动相为0.008mo1/L磷酸缓冲液,流速为3ml/min;分析流动相为甲醇—0.008mol/L磷酸缓冲液—0.05mol/L四丁基溴化铵(25:75:4)。紫外检测波长为280nm。皮下组织液及血浆中的线性范围分别为100～3200ng/ml(r=0.9999)和2～128μg/ml(r=0.9999);最低检测浓度分别为10ng/ml和0.25μg/ml,方法的平均回收率为102%,日内及日间偏差均小于7%。     

高效液相色谱法测定血清中苯巴比妥、苯妥英、卡马西平、氯硝基安定的浓度

目的：建立血清中苯巴比妥（PB）、苯妥英（PT）、卡马西平（CBZ）、氯硝基安定（CNZP）浓度测定的高效液相色谱。方法：以PB、PT互为内标，ODS-Hypersil柱为分析柱，甲醇-水-β-环糊精（45：55：0.01)为流动相；流速为0.8ml/min，紫外检测波长254nm。结果：PB、PT、CBZ、CNZP分离良好，最低检测浓度分别为0.25,0.5,0.05,0.015μg/ml；线性范围分别为2.5-40,2.5-40,1.25-20,0.02-0.32μg/ml；相对回收率分别为97.8%,102.1%,102.3%,103.3%；日蚋、日间RSD均小于10%。结论：该法操作简便，结果可靠，适用于临床开展药物浓度监测。     

HPLC法测定人血浆中伏立康唑的浓度

目的:建立一种快速、灵敏、准确、稳定的测定人血浆中伏立康唑浓度的方法,用于伏立康唑临床治疗药物监测。方法:采用高效液相色谱(HPLC)-紫外检测法,以卡马西平为内标,乙腈蛋白沉淀法处理血浆样品。色谱柱为Phecda C18,流动相为20mmol/L磷酸二氢钾缓冲液(p H=6.0)-乙腈(50∶50,V/V),流速为1 ml/min,柱温为40℃,检测波长为255 nm,进样量为50μl。结果:伏立康唑和卡马西平的保留时间分别为8.34和6.24 min;血浆中伏立康唑线性范围为0.10~20.00μg/ml(r=0.999 5),定量下限为0.05μg/ml,日内、日间RSD分别为≤1.57%、1.45%,低、中、高梯度浓度提取回收率在81.40%~128.29%之间。结论:该方法操作简便,结果准确,适用于伏立康唑的临床治疗药物监测。     

同时检测多种抗癫痫药物方法概述

抗癫痫药物的血药浓度与疗效和毒副反应密切相关。药物的治疗血浓度(如卡马西平6～10μg/ml,苯妥英10～20μg/ml,扑痫酮8～12μg/ml)和毒性浓度(如卡马西平>15μg/ml,苯妥英>25μg/ml,扑痫酮>15μg/ml)相近,用药剂量个体差异较大,临床上又常见几种抗癫痫药物同时使用,故有必要建立同时检测血药浓度的方法。由此逐步实现给药方案的合理化和用药剂量的个体化。     

高效液相色谱法测定人血清美西律浓度

目的:用高效液相色谱法测定血清中盐酸美西律浓度。方法:以卡马西平为内标,采用C_(18)柱及保护柱;流动相为甲醇:磷酸缓冲液(55:45v/v),含乙腈0.5％(v/v);流速为0.6ml/min;提取液为正庚烷;采用紫外检测,检测波长为220nm。结果:美西律与内标分离良好,保留时间分别为9.64min和14.18min;在血清中提取的绝对回收率为84.61％;盐酸美西律在0.3～3.0μg/ml范围内线性关系良好,相关系数γ=0.9998,回归方程为Y=2.4337X-0.2595;日内及日间变异均<6％;最低检测浓度为 0.025μg/ml。结论:本方法适用于盐酸美西律的药物动力学研究。     

皮肤渗透液中石杉碱-甲含量的HPLC法测定

HPLC法测定皮肤渗透液中石杉碱-甲的含量,采用外标法定量,流动相:甲醇-水(50:50V/V);紫外检测波长313nm,流速:1ml/min;柱温30℃;线性范围:0.1μg/ml～10μg/ml(r=0.9999)平均回收率99.62%(CV%=1.52%),为皮肤渗透液中石杉碱-甲含量测定的良好方法。     

反相高效液相色谱法测定苯巴比妥血药浓度

目的:建立一种快速测定苯巴比妥血药浓度的方法.方法:采用反相高效液相色谱法,以卡马西平为内标,测定苯巴比妥协药浓度.色谱柱shimadzu Shimpack CLC-C_(18)不锈钢柱,流动相为甲醇一水(60:40),流速0.8ml/min,检测波长254nm.结果:在5~40μg/ml浓度范围内线性良好(r=0.9999),最低检测限为11.57ng/ml高、中、低三种浓度的平均回收率分别为100.24%,100.28%,99.41%,RSD分别为0.7%,2.7%,5.8%(n=9).日内和日间平均RSD分别为3.3%,5.2%,8.7%和7.3%,7.3%,9.2%(n=9).结论:该方法准确、快速、简便,灵敏度高,重现性好,可作为苯巴比妥血药浓度监测的常规方法.     

皮肤渗透液中石杉碱-甲含量的HPLC法测定

HPLC法测定皮肤渗透液中石杉碱-甲的含量,采用外标法定量,流动相:甲醇-水(50:50V/V);紫外检测波长313nm,流速:1ml/min;柱温30℃;线性范围:0.1μg/ml～10μg/ml(r==0.9999)平均回收率99.62%(CV%=1.52%),为皮肤渗透液中石杉碱-甲含量测定的良好方法。     

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.

     

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.     

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.     

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.