反相高效液相色谱法同时测定血浆中氯胺酮,苯巴比妥和阿托品的浓度

本文采用ＺｏｒｂａｘＣ８色谱柱，甲醇－磷酸盐缓冲液（６９∶３１）为流动相，２２０ｎｍ为检测波长，非那西丁为内标，建立了同时测定人血浆中氯胺酮、苯巴比妥和阿托品浓度的反相高效液相色谱法。本法简便、快速、灵敏、重现性好。氯胺酮、苯巴比妥和阿托品的平均回收率分别为９９．２０％，９９．１３％和９７．６２％；不同浓度水平测定结果的日内和日间相对标准偏差均小于５％；其检测限分别为０．２μｇ／ｍｌ，０．０５μｇ／ｍｌ和０．５μｇ／ｍｌ（Ｓ∶Ｎ＝３∶１）。     

血浆中格列齐特的HPLC测定及药代动力学研究

本文采用Ｚｏｒｂａｘ Ｃ８色谱法，甲醇－０．２％冰醋酸（６２：３８）为流动相，２２９ｎｍ为检测波长，甲苯磺丁脲为内标，乙酸乙以血浆药物，建立了测定血浆中格列齐特浓度的ＨＰＬＣ法。该法简便，灵敏、快速，准确，格列齐特在０．２５￣８．０μｇ／ｍｌ的浓度范围内线性关系良好（ｒ＝０．９９１），检测限为０．１５μｇ／ｍｌ（Ｓ／Ｎ＝３：１）。平均回收率为９７．６０％，不同浓度水平测定结果的日内和日间精密度（Ｒ     

RP－HPLC法测定人血清中卡马西平及其环氧化物

用ＲＰ－ＨＰＬＣ法测定人血清中卡马西平（ＣＢＺ）及活性代谢产物卡马西平１０，１１－环氧化物（ＣＢＺ－Ｅ）的含量。血清样品用乙醚－二氯甲烷（３：１，Ｖ／Ｖ）混合溶剂提取，以硝基安定为内标，乙腈－水（４０：６０，Ｖ／Ｖ）为流动相，流速为１．２０ｍｌ／ｍｉｎ，ＵＶ２１５ｎｍ处测定；ＣＢＺ－Ｅ和ＣＢＺ最低检测浓度分别为５０和６０ｎｇ／ｍｌ；线性范围为０．１～５．０μｇ／ｍｌ和０．２～２０μｇ／ｍｌ；ＲＳＤ在５％以下。应用本法测定了８名癫痫病人单一服用ＣＢＺ治疗血清中ＣＢＺ和ＣＢＺ－Ｅ的浓度。     

高效液相色谱法测定血浆中硫唑嘌呤和巯嘌呤浓度

本文报道用高效液相色谱法测定人血浆中硫唑嘌呤和巯嘌呤浓度的方法。样品用三氯醋酸沉淀蛋白后，取上清液直接进样。以ＳｐｈｅｒｉｓｏｕｂＣ１８为固定相，甲醇－水－乙二胺（２００：８００：１０Ｖ／Ｖ）为流动相，检测波长为ＵＶ３１３ｎｍ，甲硝唑为内标。硫唑嘌呤和巯嘌呤最低检出浓度分别为０．１μｇ／ｍｌ和０．５μｇ／ｍｌ；平均回收率分别为９６．６±２．７２和１０３．４±２．６５。     

奥沙普秦及其片剂的HPLC测定

建立了测定奥沙普秦及其片剂含量的高效液相色谱法。采用Ｓｈｉｍ－ｐａｃｋ ＣＬＣ－ＯＤＳ为色谱柱，甲醇－水（７８：２２）为流动相，流速１．０ｍｌ／ｍｉｎ，检测波长为２５４ｎｍ，以二苯胺为内标。结果表明奥沙普秦在１３￣７６μｇ／ｍｌ浓度范围内奥沙普秦与内标物峰面积之比与其浓度呈良好线性关系，ｒ＝０．９９９９。精密度试验ＲＳＤ０．１９％，方法回收率为１００．１％。     

HPLC测定收缴海洛因的含量

采用高效液相色谱法测定海洛因的含量，色谱柱：Ｎｏｖａ－ｐａｋＣ１８柱，流动相０．０５ｍｏｌ／Ｌ磷酸氢二钠－磷酸二氢钠：乙腈，流速：２．０ｍｌ／ｍｉｎ紫外检测波长为２１４ｎｍ，在海洛因浓度２．９３μｇ／ｍｌ－６０００．００μｇ／ｍｌ范围内，线性良好，回归方程Ｙ＝０．０２６ｘ＋０．５２０４，ｒ＝０．９９９９，Ｙ为峰面积，ｘ为浓度。涨洛因标准品检测的日内平均标准偏差为１．４２－２．１６％；日间平均偏差     

反相高效液相色谱法测定人血浆中双氯灭痛

本文建立了用反相高效液相色谱法测定人血浆中双氯灭痛的方法，对样品提取及色谱分析条件等作了详细研究。血浆经酸化反用正己烷－异丙醇提取，以ＳｐｈｅｒｉｓｏｒｂＣ１８为固定相，甲醇与醋酸钠缓冲液的混合深液（６８：３２，Ｖ／Ｖ；ｐＨ４．２）为流动相进行色谱分离。检测波长为２７４ｎｍ，二苯胺为内标。双氯灭痛浓度在０．１０－２．５０μｇ／ｍｌ范围内线笥良好，ｒ＝０．９９９４。测定含双氯灭痛浓度为０．２０μｇ／     

气相色谱法测定卡维地洛中有机溶剂残留量

采用气相色谱法测定卡维地洛中残留溶剂甲醇、异丙醇、甲苯的含量。结果为：甲醇在１０－１６０μｇ／ｍｌ的浓度范围内,回归方程为Ｙ＝２．２８８Ｘ－０．００７２ｒ＝０．９９９８;异丙醇在１６０－８００μｇ／ｍｌ的浓度范围内,回归方程为Ｙ＝３．５４６５Ｘ＋０．０９６０ｒ＝０．９９９７,甲苯在３０－１６０μｇ／ｍｌ的浓度范围内,回归方程为Ｙ＝９．１８７５Ｘ＋０．１１７４ｒ＝１．０００。结果表明：以上各浓度范围     

盐酸普罗帕酮的荧光测定法

盐酸普罗帕酮在ｐＨ７．０的乙醇－水介质中进行测定，激发光波长３２３ｎｍ，发射光波长４１８ｎｍ。在１￣６０μｇ／ｍｌ浓度范围内，荧光强度与浓度呈线性关系。最低检测浓度０．０４μｇ／ｍｌ。本法测定成本低，选择性好，灵敏度高。     

反相高效液相色谱法同时测定血浆中苯妥英钠及其主要代谢产物的浓度

以非那西丁为内标，乙酸乙酯萃取血浆药物，甲醇－乙腈－水（４０：１０：５０，Ｖ／Ｖ）为流动相，紫外检测波长为２０３ｎｍ的色谱条件下，反相高效液相色谱法同时测定血浆中苯妥英钠及其主要代谢产物（对羟基苯妥英钠）。结果，血浆苯妥英钠及对羟基苯妥英钠在５￣３５μｇ／ｍｌ和２．５￣３０μｇ／ｍｌ的浓度范围内标准曲线线性关系良好，检测限分别为２．５μｇ／ｍｌ和１．５μｇ／ｍｌ（Ｓ／Ｎ＝３：１）。还测定了家兔口服     

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.     

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.