NP-HPLC法监测人血浆中4种苯并二氮(?)药物浓度

目的:建立监测人血浆中咪达唑仑、三唑仑、艾司唑仑和阿普唑仑药物浓度的正相高效液相色谱方法。方法:血浆样品用乙醚萃取,55℃水浴中氮气吹干;残留物用乙醇溶解后进样。色谱柱为Shim-pack CLC-CN 柱(150 mm×6.0 mm,5μm),流动相为正己烷-无水乙醇-甲醇(76:18:6),流速为1.10 mL·min-1,柱温为:40℃,紫外检测波长为230 nm。结果:本方法可用于同时测定血浆中4种药物的浓度。咪达唑仑、三唑仑、艾司唑仑和阿普唑仑在0.050-20.0μg·mL-1范围内线性关系良好(r≥0.9996),准确度分别为98.9％,99.8％,101.8％及100.5％(n=6)。日内和日间RSD均不大于5.1％(n=6)。结论:本方法灵敏、特异性强、准确、简便易行,适用于咪达唑仑、三唑仑、艾司唑仑和阿普唑仑4种药物血浓度的临床监测。     

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     

RP-HPLC同时测定血浆中8种苯二氮(艹卓)类药物

目的 采用HPLC法建立同时测定血浆中8种苯二氮(艹卓)类药物(氯硝西泮、艾司唑仑、阿普唑仑、三唑仑、澳沙西泮、替马西泮、氯氮(艹卓)和地西泮)的方法.方法 血浆样品经正己烷-二氯甲烷(5:3)提取.选用Diamonsil Rp-C18柱(250 mm×4.6mm,5μm);甲醇-25 mmol.L-1醋酸铵溶液(63:37)作流动相,流速1.0 mL·min-1,检测波长230 nm.结果 氯硝西泮、三唑仑、澳沙西泮、氯氮(艹卓)、地西泮的最低检测浓度为8μg·L-1,艾司唑仑、阿普唑仑、替马西泮的最低检测浓度为5μg·L-1;方法回收率接近100%;提取回收率大于70%,日内、日间精密度小于6%;艾司唑仑、阿普唑仑和替马西泮10～1.5×103μg·L-1的线性关系良好,其余5种药物的线性范围为20～1.5×103μg·L-1(r＞0.999).结论 所建方法操作简便、快速、准确、灵敏度高、重复性好,适用于临床上人血浆中8种苯二氮(艹卓)类药物的同时定性、定量检测.     

RP-HPLC法同时测定血浆中艾司唑仑和阿普唑仑的浓度

目的　建立反相 HPL C法同时测定血浆中艾司唑仑 (EZ)和阿普唑仑 (AZ)浓度的方法。 方法 　以 Techsphere-ODS色谱柱为分析柱 ,甲醇 -水 (65∶ 3 5 )为流动相 ,硝西泮 (NZ)为内标 ,紫外 2 5 4nm处检测。结果 　 EZ和 AZ血浓线性范围为 0 .2 5～ 3 .0μg· ml- 1 ,最低检测浓度分别为 12 .5 ng/ml、12 .5 ng/ml,日内和日间精密度均小于 7%,平均回收率分别为 10 1.5 0 %,96.14 %。 结论 　本法可用于临床血药浓度测定     

HPLC法同时测定人血浆中7种苯二氮(艹卓)类药物的浓度

目的:建立HPLG法同时测定人血浆中地西泮、硝西泮、氯硝西泮、咪达唑仑、三唑仑、艾司唑仑和阿普唑仑的浓度.方法:血浆样品用乙醚萃取,55℃水浴中N2吹干,残留物用乙醇溶解后进样.色谱柱为Shim-pack CLC-CN柱(150 mm×6.0mm,5μm),流动相为正己烷-无水乙醇-甲醇(87.8:10.2:2,V/V/V),流速1.10 mL·min-1,柱温40℃,检测波长240 nm.结果:硝西泮、氯硝西泮在0.02～20.0 mg·L-1范围内线性关系良好(r≥0.999 3),地西泮、咪达唑仑、三唑仑、艾司唑仑和阿普唑仑在0.05～20.0 mg·L-1范围内线性关系良好(r≥0.999 7).方法回收率近100%,日内和日间RSD均≤7%(n=5).结论:本方法适用于人血浆中7种苯二氮(艹卓)类药物同时检测.     

HPLC法同时测定人血浆中7种苯二氮类药物的浓度

目的建立HPLG法同时测定人血浆中地西泮、硝西泮、氯硝西泮、咪达唑仑、三唑仑、艾司唑仑和阿普唑仑的浓度.方法血浆样品用乙醚萃取,55℃水浴中N2吹干,残留物用乙醇溶解后进样.色谱柱为Shim-pack CLC-CN柱(150 mm×6.0mm,5μm),流动相为正己烷-无水乙醇-甲醇(87.810.22,V/V/V),流速1.10 mL·min-1,柱温40℃,检测波长240 nm.结果硝西泮、氯硝西泮在0.02～20.0 mg·L-1范围内线性关系良好(r≥0.999 3),地西泮、咪达唑仑、三唑仑、艾司唑仑和阿普唑仑在0.05～20.0 mg·L-1范围内线性关系良好(r≥0.999 7).方法回收率近100%,日内和日间RSD均≤7%(n=5).结论本方法适用于人血浆中7种苯二氮(艹卓)类药物同时检测.     

酶水解-HPLC法同时测定尿中三唑仑及其代谢物

目的 :用酶水解 HPLC方法同时测定尿中三唑仑及其主要代谢物α 羟基三唑仑。方法 :尿样 2mL ,加 β 葡萄糖醛酸苷酶 0 2 5mL ,5 5℃酶解 2h ,用正己烷 二氯甲烷 (5∶3,v/v) 5mL提取 ,挥干提取溶剂后用 5 0 μL甲醇溶解 ,10 μL进样 ,HPLC检测。结果 :本法对三唑仑和α 羟基三唑仑的最低检测限均为 4ng·mL-1;绝对回收率分别为 93 12 %和 6 7 70 % ;日内、日间RSD分别在 6 0 8%和 11 0 5 %以下 ;线性范围均为 12 5～ 375 0ng·mL-1。结论 :酶水解提高了α 羟基三唑仑的检出率 ,从而使本法能同时测定尿中三唑仑及α 羟基三唑仑 ,此法重现性好、灵敏、可靠 ,可用于三唑仑滥用中毒及有关案例的检测     

HPLC法测定艾司唑仑血药浓度的方法验证

目的:建立测定艾司唑仑血药浓度的方法,以确定较好的检测条件。方法:采用高效液相色谱法,以依利特Hypersil ODS2 C18为色谱柱,甲醇-乙腈-水(28∶28∶54)为流动相,1.0 mL·min-1为流速,35℃为柱温,230 nm为检测波长,地西泮为内标,考察服用艾司唑仑片患者血浆、碱化血浆、血清浓度并对选定的标本及提取方法进行验证。结果:艾司唑仑血浆浓度明显高于碱化血浆及血清浓度,经成对双侧t检验,艾司唑仑血浆浓度与碱化血浆及血清浓度比较(P分别为0.011 30、0.018 17),有显著性差异。艾司唑仑血药浓度在0.049 4～1.289 6μg·mL-1范围内线性关系良好(r=0.991 8),定量下限为0.049 4μg·mL-1;平均日内、日间RSD均<10%,平均回收率为99.95%～100.79%。结论:采用患者血浆作为标本进行艾司唑仑血药浓度监测和药物中毒的定量分析可行,本方法简便、准确。     

HPLC法测定地西泮和艾司唑仑的血药浓度

目的:建立HPLC法同时测定地西泮和艾司唑仑血药浓度。方法:以Ultrasphere ODS 5 μm 4 .6mm×2 5cm色谱柱为分离柱,流动相:甲醇 乙腈 水( 4 0∶2 0∶4 0 ) ;检测波长为2 5 4nm ,以外标法峰面积定量。结果:地西泮和艾司唑仑的血浓度分别在0 .2 1 4～2 .5 6 8μg/ml,0 .2 5 8～3.0 96 μg/ml范围内与峰面积呈良好的线性关系,日内及日间差均小于1 0 % ,平均回收率分别为98.37% ,99.1 9%。结论:本法可用于临床血药浓度测定。     

HPLC同时测定人血浆中4种苯二氮类药物的浓度

目的 采用HPLC同时测定人血浆中地西泮、氯硝西泮、三唑仑、艾司唑仑的浓度.方法 血浆样品经氢氧化钠碱化后用乙酸乙酯萃取,氮气吹干,残留物用甲醇溶解后进样.采用Alhech-C18色谱柱,流动相为乙腈-甲醇-水(30:30:40),流速为1.0 ml·min-1,检测波长为225 nm.结果 三唑仑0.05-10.00 mg·L-1与峰面积的线性关系良好(r=0.9998),地西泮、艾司唑仑和氯硝西泮0.1～20.0 mg·L-1与峰面积的线性关系良好(r=0.9997).4种成分的方法回收率分别为96.8%、92.6%、97.7%、94.8%;13内和日间RSD均小于10%(n=5).结论 所建方法操作简便、快速、准确、灵敏度高、重复性好,适用于临床上人血浆中4种苯二氮(艹卓)类药物的同时定性、定量检测.     

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.