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.     

自动柱切换高效液相色谱法同时测定血浆中的SMZ和TMP

应用自制自动柱切换装置建立了同时测定SMZ及TMP血药浓度的HPLC方法.采用μBondapak C 18(50mm×4.6mm.37～50μm)为预处理柱,水为预处理流动相.分析柱为Hypersil BDS C18(150mm×4.6mm,5μm)柱,分析流动相为甲醇:磷酸缓冲液=35:65.检测波长230nm.SMZ和TMP分别在2.5～80μg/ml及0.125～4μg/ml范围内线性良好(r_1=0.999 7,r_2=0.9998).平均方法回收率分别为98.59%及95.71%;日内精密度分别为2.11%及2.67%,日间精密度分别为2.51%及2.89%;两者的最低血浆检测浓度可达SMZO.1μg/ml,TMPO.02μg/ml.方法迅速、简便、灵敏.     

高效液相色谱法测定复方氯唑沙宗片中两组分血药浓度

目的:研究建立测定血浆中复方氯唑沙宗片两组分浓度的HPLC-UV法。方法:反相高效液相色谱法测定血浆中药物的浓度。Zorbax XDB-C18色谱柱,血浆样品经乙醚提取,空气吹干,加流动相溶解进样。氯唑沙宗的流动相为甲醇∶水=(60∶40),在波长282nm处检测;对乙酰氨基酚的流动相为甲醇∶水=(20∶80),在波长245nm处检测,以外标法计算。结果:氯唑沙宗在0.208～33.28μg/ml、对乙酰氨基酚在0.238～14.28μg/ml浓度范围内,样品的峰面积与对应浓度呈良好线性关系,r氯=0.9998,r对=0.9998。最低检测限均为0.1μg/ml,氯唑沙宗高、中、低(20.8μg/ml,4.16μg/ml,0.416μg/ml)3种浓度的方法回收率分别为(103.36±6.0)%,(99.51±1.2)%,(99.08±1.88)%;对乙酰氨基酚高、中、低(9.52μg/ml,2.38μg/ml,0.476μg/ml)3种浓度的方法回收率依次为(101.5±3.15)%,(97.6±1.93)%,(99±3.15)%,日内RSD分别为(1.2%～2.3%)、(1.4%～6.7%),日间RSD分别为(2.5%～5.1%)、(5%～7.8%)。结论:此法操作简便、结果可靠。     

气相色谱法检测二氯甲烷中微量挥发性杂质

目的 建立二氯甲烷中三氯甲烷、四氯化碳、1,2-二氯乙烷三种有机挥发性残留杂质的分析方法.方法 采用程序升温气相色谱法进行,运用DB-5色谱柱、电子捕获检测器(ECD),检测器温度为250℃.结果 三氯甲烷、四氯化碳、1,2-二氯乙烷和二氯甲烷间能够完全分离(分离度＞3.0),线性范围:三氯甲烷0.5-5.0μg/ml,r=0.997;1,2-二氯乙烷2.7～27.0μg/ml,r=0.999;四氯化碳0.025～0.5μg/ml,r=0.999.平均回收率为:三氯甲烷98.6%;1,2-二氯乙烷103.5%;四氯化碳94.4%.检测限:三氯甲烷0.02μg/ml;1,2-二氯乙烷0.10μg/ml;四氯化碳0.001μg/ml.结论 经方法学验证,该方法灵敏度、准确度均能满足ICH对药品中Ⅰ类、类Ⅱ残留溶剂检测的要求,可用于同时检测二氯甲烷中微量的三氯甲烷、1,2-二氯乙烷和四氯化碳残留.     

高效液相色谱法测定血清及尿中卡那霉素含量

本文研究了血清及尿中卡那霉素的高效液相色谱测定法。血样用乙腈去蛋白、尿样用水稀释后,经邻苯二醛衍生化,衍生物经色谱分离,荧光检测。最低检测浓度:血样为0.2μg/ml,尿样为2μg/ml;平均回收率:血样为98.3%(SD=4.1),尿样为98.2%(SD=2.3);日内变异系数:血样及尿样均低于4%;日间变异系数:血样不大于5.4%,尿样不大于5.7%;线性浓度范围:血样为4～40μg/ml,尿样为50～500μg/ml。     

HPLC法测定含有多种维生素类制剂中四种维生素含量

目的:建立HPLC法测定含有多种维生素类制剂中四种维生素(维生素B1、维生素B2、维生素B6、烟酰胺)的含量.方法:采用C18柱,以0.05mol/L己烷磺酸钠溶液(用冰醋酸调节pH值为3.0)-甲醇(80:20)为流动相,流速为1.0ml/min.紫外检测波长为254nm.结果:本实验中维生素B1、维生素B2、维生素B6、烟酰胺线性范围分别为4～20μg/ml(r=0.9997),4～20μg/ml(r=0.9998),0.8～4μg/ml(r=0.9997),32～160μg/ml(r=0.9999),方法的回收率在98.5%～100.4%,RSD为0.23%～1.10%.各组分间的分离度均符合要求.结论:本方法快速、简便、准确,分离效果好,辅料无干扰,适用于该类制剂中四种维生素组分同时测定.     

阿替洛尔与硝苯地平复方片的HPLC测定

采用高效液相色谱法测定复方阿替洛尔片中阿替洛尔与硝苯地平的含量.色谱柱为Kromasil C18,流动相为甲醇-水-磷酸盐缓冲液(pH3.0)(55:42:3,含6.0 mmol/L辛烷磺酸钠),流速0.8ml/min,检测波长274 nm.阿替洛尔和硝苯地平的线性范围分别为20～80μg/ml和8～32μg/ml,平均回收率分别为100.2%(RSD 0.45%)和100.4%(RSD 0.77%).     

HPLC法同时测定血清中苯妥英,卡马西平的浓度

本实验建立了用反相HPLC 法同时测定人血清中苯妥英及卡马西平的方法。以苯乙酮为内标,采用Ultrasphere ODS 柱(5μm)(φ4.6×150mm),甲醇:水(50:50)为流动相流速0.8ml/min 紫外210nm 检测,血清处理用于乙腈沉淀蛋白,样品预处理过程快速简便,整个过程仅需20min 即可检出。苯妥英最低检测浓度为0.626μg/ml,相对回收率为99.66～102.40%线性范围为1.252～40.06μg/ml,相关系数r=0.9999:卡马西平最低检测浓度为0.5μg/ml,相对回收率为101.28～103.93%,线性范围为1.274～20.38μg/ml,相关系数r=0.9999。将本法应用于临床治疗药物监测获得满意效果。     

注射用头孢他啶中头孢他啶与精氨酸的HPLC法测定

建立了HPLC法测定注射用头孢他啶中的头孢他啶与精氨酸.采用C18色谱柱,以乙腈-0.5 mol/L磷酸盐缓冲液(pH 7.0)-0.14%戊烷磺酸钠溶液(40:200:1 760)为流动相,检测波长206nm.头孢他啶和精氨酸在10～800μg/ml和4～290μg/ml浓度范围内线性关系良好,回收率为99.8%和99.5%,RSD为0.4%和1.0%.     

高产液相色谱法测定复方利福平片中利福平、异烟肝及吡嗪酰胺的含量

用HPLC法测定复方利福平片中利福平、异烟肼及吡嗪酰胺的含量.方法采用Spherisorb CN(250mm×4.6mm,5μm)色谱柱,流动相采用0.01mol/L庚烷磺酸钠溶液(pH2.2)-乙腈(4456,v/v),流速为2.0ml/min,检测波长为254nm.结果利福平在71.76～166.40μg/ml、异烟肼在47.64～111.16μg/ml、吡嗪酰胺在137.76～321.44μg/ml范围内线性良好,r分别为0.9999、0.9991、0.9999(n=9),平均回收率分别为99.57%、99.51%、100.10%,RSD分别为0.71%、0.51%、0.62%(n=7).结论本法简便、准确、灵敏度高.     

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.