血浆中单硝酸异山梨酯的高效液相色谱法测定

目的 :建立了高效液相色谱法测定血浆中单硝酸异山梨酯浓度。方法 :采用硅胶分析柱 ,以二氯甲烷 -正己烷 -乙腈 -甲醇 (92∶4∶1 5∶2 5 )为流动相 ,卡马西平作内标。样品在碱性条件下用二氯甲烷萃取浓集后进样 ,2 34nm波长下检测 ,按内标法定量。结果 :标准曲线在 2 5～ 16 0 0 μg·L-1范围内有良好线性 ,最低检测浓度为 10 μg·L-1,方法回收率为 96 %～ 10 4% ,日内RSD小于 4 5 % ,日间RSD小于 5 %。结论 :本法具有快速简便 ,灵敏准确等特点 ,已用于单硝酸异山梨酯缓释制剂生物利用度测定 ,结果良好。     

反相高效液相色谱法测定血浆中文拉法辛浓度

目的 :建立高效液相色谱法检测人血浆中文拉法辛浓度。方法 :血浆样品经石油醚 乙醚 (2∶1 )提取后 ,有机相再用50mmol·L- 1盐酸反萃取并浓缩进样。色谱柱为氰基柱 (2 50× 4.6mm ,5μm) ,乙腈 -0 .1mol·L- 1NH4 H2 PO4 (2 5∶75)为流动相 ,UV检测波长 2 2 9nm。结果 :文拉法辛血浆最低检测浓度 1 0 μg·L- 1,线性范围 2 5～ 80 0 μg·L- 1,萃取回收率 75.5%～79.3%,加样回收率 97.4%～ 1 0 1 .2 %,日内RSD 4.87%～ 6 .39%,日间RSD 7.55%～ 1 0 .80 %。结论 :该法准确可靠 ,已用于临床患者文拉法辛血药浓度测定。     

高效液相色谱法测定血浆缬沙坦浓度

目的　建立一种高效液相色谱法以测定血浆中缬沙坦浓度。方法　色谱柱 :LichrospherC18高效液相柱 ;流动相 :0 0 1mol·L-1磷酸二氢钾缓冲液 (pH 3 1)∶乙腈 =5 3∶4 7(V/V) ,流量 1 0ml·min-1;检测器 :荧光检测 ,激发波长2 6 5nm ,发射波长 378nm。血浆样品经盐酸酸化 ,乙酸乙酯萃取 ,分离有机相 ,氮气吹干 ,流动相溶解后进样。结果　缬沙坦保留时间为 12 5min ,分离良好 ;标准曲线在 5 9～2 36 0 μg·L-1范围内呈线性 ;日间RSD为 5 94 %～ 8 4 1% ,日内RSD为 2 83%～ 7 0 7% ,回收率为 81 13%± 5 2 6 %。选择住院高血压病人 15例 ,每日口服缬沙坦胶囊 80mg ,分别于第 4、7d测定其稳态峰、谷浓度 ,谷浓度为 (16 5 99±6 0 2 2 ) μg·L-1,峰浓度为 (5 2 6 90± 337 0 6 ) μg·L-1。结论　该法灵敏、简便 ,适用于血药浓度监测及其动力学研究     

RP-HPLC测定母体及胎儿血浆中罗哌卡因和布比卡因的药物浓度

目的 :建立罗哌卡因、布比卡因血浆药物浓度的反相高效液相 (RP HPLC)测定方法 ,并测定其母体和 (或 )胎儿血药浓度 ,为临床合理用药提供参考。方法 :采用AgilentHPLC系统 ;色谱柱 :Dikma C18(5 μm ,4 .6× 15 0mm)。以罗格列酮作为内标 ,流动相为磷酸二氢钠缓冲液 (10mmol·L- 1,pH3.0 )∶乙腈 =78∶2 2 ,流速 1.0mL·min- 1,λ =2 10nm。结果 :罗哌卡因线性关系为Y =0 .0 2 95X -0 .0 2 98(n =7,r =0 .9998) ;最低检测浓度为 0 .0 1mg·L- 1;平均回收率为 99.82 % ;日内、日间RSD分别小于 2 .4 7% ,3.75 % ;布比卡因线性关系为Y =0 .0 2 87X + 0 .0 2 71(n =7,r =0 .9998) ;最低检测浓度为 0 .0 1mg·L- 1;平均回收率为 10 1.0 1% ;日内、日间RSD分别小于 2 .6 9% ,4 .75 %。测定 6 0个血样 ,罗哌卡因浓度为 0 .15～ 0 .7mg·L- 1,布比卡因为 0 .1～ 0 .5 8mg·L- 1。结论 :RP HPLC法简便、灵敏、准确 ,可以用来测定临床血样中罗哌卡因、布比卡因的药物浓度 ,可为临床合理用药提供参考。     

高效液相色谱法测定异丁司特的血药浓度

目的 :建立高效液相色谱法测定人血浆中异丁司特浓度的方法。方法 :采用YWG C18色谱柱 ,以甲醇 0 .0 5mol·L-1磷酸二氢钾 (6 5∶35 ,用磷酸调pH值 3.5 )为流动相 ,检测波长 2 2 5nm ,流速 1.0mL·min-1,进样量 5 0 μL ,内标物为桂利嗪。 结果 :异丁司特标准曲线在 2～ 12 0 μg·L-1范围内线性关系良好 (r =0 .995 6 ) ,最低检测浓度为 2 μg·L-1,平均回收率为10 0 .2 % ,RSD为 4 .7% (n =5 )。结论 :该法操作简便 ,灵敏 ,准确度高 ,适用于异丁司特血药浓度的测定和药动学的研究。     

液相色谱-串联质谱法测定人血浆中罗格列酮

目的:建立测定人血浆中罗格列酮的液相色谱-质谱-质谱联用法,并用于临床药动学研究。方法: 血浆样品经液-液萃取后,以乙腈-水-甲酸(90:10:0．5)为流动相,采用Zorbax SB—C18柱分离,通过电喷雾离子化四极杆串联质谱,以选择反应监测(SRM)方式进行检测。用于定量分析的离子反应分别为m／z 358→ 135(罗格列酮)和m／z 256→167(内标苯海拉明)。结果:标准曲线线性范围为0．50～1 000μg·L-1,定量下限为0．50μg·L-1,日内、日间精密度(RSD)均小于7．4％。应用此法测试了20名男性健康受试者口服酒石酸罗格列酮片(相当于罗格列酮4 mg)后血浆中罗格列酮的浓度。结论:该法灵敏、快速、准确,操作简便、线性范围宽,适用于罗格列酮的临床药动学研究。     

高效液相色谱法测定血清中胺碘酮浓度

目的 　建立反相高效液相色谱法测定人血清中胺碘酮的浓度。方法 　采用液 -液提取 ,流动相为甲醇∶水∶三乙胺 (2 0 0∶ 3 6∶ 0 .1) ,醋酸调 p H值至 7.15 ,检测波长 2 40 nm。结果 　线性范围为 0 .4～ 4μg· m L- 1 平均回收率 10 1.6% ,日内 RSD小于 6% ,日间 RSD小于 9%。结论 　本方法操作简便、快速、准确 ,适用于生物样品中胺碘酮的血药浓度监测。     

RP-HPLC测定大鼠血浆中水飞蓟宾的浓度

目的　测定大鼠血浆中水飞蓟宾的浓度。方法　用RP -HPLC。样品以叔丁基甲醚提取 ,色谱柱为PoresphereC18柱 (4.0mm× 2 5 0mm ,5 μm) ,流动相为甲醇 水 0 .0 5mol·L-1磷酸二氢钾 (2 0∶10∶7) ,流速为 1.0ml·min-1,检测波长为 2 88nm ,温度为室温。结果　大鼠血浆中成分对水飞蓟宾的测定无干扰 ;在 0 .0 0 6 1～ 3.12 5 μg·ml-1浓度范围内呈现良好的线性关系 ,r=0 .9992 ;血浆中水飞蓟宾的最低检测浓度为 6ng·ml-1,平均回收率为10 7.0 0 % ,日内RSD≤ 8.19% ,日间RSD≤ 13.78%。结论　该法样品处理简便 ,灵敏度高 ,结果准确。     

HPLC法同时测定血浆地西泮及其代谢物浓度

目的 :建立同时测定血浆中地西泮及其代谢物浓度的方法。方法 :选用ZORBAXRP C18柱 (15 0mm× 4 6mm ,5 μm) ;甲醇 - 2 5mmol·L-1醋酸铵溶液 (6 0∶4 0 ,V/V)作流动相 ;流速 0 8mL·min-1;检测波长 2 30nm。取血浆样品 0 5mL ,在碱性条件下用二氯甲烷 -正己烷提取 ,HPLC检测。结果 :本法对替马西泮、去甲地西泮和地西泮 3种物质的最低检测限均为 2 μg·L-1,线性范围为 10～ 15 0 0 μg·L-1;奥沙西泮的最低检测限为 5 μg·L-1,线性范围为 2 0～ 15 0 0 μg·L-1。回收率均接近 10 0 % ,日内、日间RSD <5 %。结论 :本法能同时测定血浆中地西泮及其代谢物浓度 ,具有重现性好 ,灵敏、可靠 ,可用于地西泮中毒的监测     

高效液相色谱法测定马来酸罗格列酮片的含量

目的建立高效液相色谱法测定进口马来酸罗格列酮片的含量。方法色谱柱:HypersilC18柱(150×4.6mm,5μm);流动相:乙腈-0.01mol·L-1乙酸铵(50∶50),流速1.0mL·min-1,紫外检测波长:247nm。结果罗格列酮在10~200μg·mL-1浓度范围内线性良好(r=0.9999,n=3);加样回收率为99.61%,RSD为1.02%(n=6)。结论本法快速、简便、准确、重复性好。     

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.