离子对RP-HPLC测定盐酸丁螺环酮缓释片中主药的含量

目的　测定盐酸丁螺环酮缓释片中盐酸丁螺环酮的含量。方法　采用离子对反相高效液相色谱法。Nova PakC18色谱柱 ,流动相为甲醇 -乙腈 -离子溶液 (十二烷基硫酸钠 2 5g ,二乙胺 1ml,加水至 10 0 0ml,冰醋酸调pH 3 0 ) (10∶5 0∶4 0 ) ,检测波长为 2 6 5nm。结果　盐酸丁螺环酮的含量在 0 32～ 1 6 μg·ml-1浓度范围内线性关系良好 (r =0 9999)。平均回收率 97 5 6 %(n =5 )RSD =1.13%。结论　所用方法简便、快速、准确。     

RP-HPLC法同时测定复方石韦胶囊中5种成分的含量

目的:建立高效液相色谱法同时测定复方石韦胶囊中香草酸、绿原酸、芦丁、苦参碱和氧化苦参碱的含量。方法:采用Gemini-C_(18)(250mm×4.6mm,5.0μm)色谱柱;以甲醇(A)-0.04%三乙胺(pH=6.65)(B)为流动相,采用梯度洗脱程序:0min,A-B(15:85);10min,A-B(60:40);13 min,A-B(80:20)。流速为0.8 mL·min~(-1);柱温为27℃;二极管阵列检测波长为220,270,326nm。结果:香草酸、绿原酸、芦丁、苦参碱和氧化苦参碱的线性范围分别为1.14～17.14μg·mL~(-1)(r=0.999 3),4.28～51.42μg·mL~(-1)(r=0.998 0),3.97～43.67μg·mL~(-1)(r=0.999 8),0.06～0.72mg·mL~(-1)(r=0.999 6),9.8～68.6μg·mL~(-1)(r=0.999 6);加样回收率分别为100.1%(RSD<2.4%),99.4%(RSD<1.3%),99.5%(RSD<2.4%),99.9%(RSD<72.8%),100.3%(RSD<2.2%)。结论:该检测方法为复方石韦胶囊的质量控制提供了科学依据。     

混合取代基—β—环糊精—毛细管电泳法分离测定麻黄碱和伪麻黄碱

目的:建立毛细管电泳法同时分离测定同分异构的2对手性化合物麻黄碱和伪麻黄碱的含量。方法:Waters CapillaryIon Analyzer,50μm×60cm空心熔融石英毛细管柱,柱上紫外检测。电泳条件:分离用缓冲液为25mmol·L~(-1)的磷酸-Tris 缓冲液,含18mmol·L~(-1)的羧甲基-β-环糊精和7.5mmol·L~(-1)的β-环糊精-硫酸酯,pH3.02。分离电压:18kV;温度:25℃;虹吸进样,高度10cm,时间1s;紫外检测波长214nm。结果:左旋伪麻黄碱、右旋麻黄碱、左旋麻黄碱和右旋伪麻黄碱线性范围分别为23.7～237μg·ml~(-1),25.0～250μg·mL~(-1),25.0～250μg·mL~(-1),25.4～254μg·mL~(-1),以信噪比等于3:1为标准,最小检测浓度均为5.0μg·mL~(-1);日内和日间精密度RSD在2.4％～4.3％之间。结论:方法分离效率高、简便、快速、成本低。     

HPLC法测定人血浆中劳拉西泮的浓度

目的:建立测定人血浆中劳拉西泮浓度的HPLC法。方法:采用美国Dikma公司Diamonsil~(TM)C_(18)(250mm×4.6mm,5μm)为色谱柱,流动相为甲醇-水(75:25,V/V),流速为0.8mL·min~(-1),检测波长232mm,以乙酸乙酯为提取溶剂。结果:劳拉西泮高(20.00μg·mL~(-1))、中(6.00μg·mL~(-1))、低(0.60μg·mL~(-1))3个浓度的平均回收率分别为101.67％,98.17％,91.20％,日内、日间RSD均<5％(n=5);分析方法的定量测定下限为0.O05μg·mL~(-1)。线性范围为0.01～20.00μg·mL~(-1),回归方程为Y=2.16×10~(-2)X-3.33×10~(-3),r=0.9999(n=10)。结论:该方法灵敏、准确、简单、快速,可用于劳拉西泮临床血药浓度监测和药动学研究。     

人血浆中富马酸奎硫平浓度的测定

目的:建立测定人血浆中富马酸奎硫平(QTP)浓度的HPLC法。方法:以Diamonsil~(TM)C_(18)柱(250mm×4.6mm,5μm)为色谱柱,流动相:甲醇-超纯水(85:15,V/V),流速为0.8mL·min~(-1),检测波长254nm,以乙酸乙酯为提取剂。结果:QTP 80.00,16.67,1.67μg·mL~(-1)高、中、低3个浓度的平均回收率分别为98.20％,101.44%,98.21％。日内、日间RSD均<5%(n=5)。分析方法的最小检测限为0.08μg·mL~(-1)(r_(SN)=2)。线性范围为0.17～100.00μg·mL~(-1),线性回归方程为Y=8.78×10~(-2)X-3.37×10~(-2),r=0.9999(n=11)。结论:该方法灵敏、准确、简单、快速,可用于临床血药浓度监测和药动学研究。     

HPLC法测定复方盐酸萘甲唑林（乎泰）喷雾剂中中盐酸萘甲唑林和马来酸氯苯那敏的含量

目的:用HPLC法测定复方盐酸萘甲唑林(乎泰)喷雾剂中盐酸萘甲唑林和马来酸氯苯那敏的含量。方法:以Spherisorb硅胶柱(250mm×5mm,10μm)为固定相,流动相为乙腈-3％醋酸-三乙胺(15:85:0.08,用醋酸或三乙胺调节pH3.0),流速为1.5 mL·min~(-1),检测波长为265nm,进样20μL,采用外标法定量。结果:盐酸萘甲唑林线性范围为40.76～163.04μg·mL~(-1),马来酸氯苯那敏的线性范围为80.04～320.16μg·mL~(-1),平均回收率分别为100.5％和100.3％。结论:本法结果准确,重现性良好,方法简便。以此方法测定的盐酸萘甲唑林和马来酸氯苯那敏含量,较原方法更合理,准确,简便。     

硝基咪唑类药物在授乳妇女中的乳药分析

目的:研究甲硝唑、替硝唑在授乳妇女乳汁中的分泌。方法:高效液相色谱法。Ultraspbere-ODS柱,甲硝唑乳药分析用流动相为乙腈-0.1％冰醋酸(50:50),替硝唑乳药分析用流动相为乙腈-水(60:40),流速1.0mL·min~(-1) ,检测波长318nm。结果:甲硝唑乳汁药物浓度在2h时为(10.11±5.390)μg·mL~(-1),8h时尚可测得(4.478±2.669)μg·mL~(-1)。替硝唑乳汁药物浓度在2h时为(14.17±5.746)μg·mL~(-1),8h时尚可测得(9.364±5.123)μg·mL~(-1)。结论:本文建立的高效液相色谱法简单、灵敏,适用于乳药浓度的测定,建议授乳妇女避开给药时间哺乳。     

大鼠口服茯苓素后血浆中的去氢土莫酸药代动力学研究

目的:建立测定大鼠血浆中去氢土奠酸浓度的高效液相色谱方法,并以去氢土莫酸为指标,研究大鼠灌胃给予茯苓素混合提取物后的药代动力学行为。方法:采用HPLC方法测定大鼠灌胃给予茯苓素混合提取物后,血浆中去氢土莫酸的浓度。色谱柱为ODS枉(200mm×4.6 mm,5μm),流动相为甲醇乙腈-2％冰醋酸水溶液(13:12:10),流速为1.0mL·min~(-1),检测波长为242nm,进样量20μL,室温下操作,内标物为丙酸睾丸素。结果:在0.20～20.0μg·mL~(-1)范围内具有良好线性关系(r=0.9981),方法回收率为85.2％～93.6％,日内、日间RSD均小于6.0％,达峰时间约为2h,峰浓度为(10.4±1.4)μg·mL~(-1),药时曲线下面积为32.6μg·mL~(-1)·h~(-1)。结论:此方法稳定、可靠,适用于茯苓素的药代动力学研究。     

高效液相色谱荧光法测定人血浆中盐酸伐昔洛韦的代谢产物阿昔洛韦

目的:建立高效液相色谱荧光分析方法测定人血浆中盐酸伐昔洛韦的代谢产物阿昔洛韦(ACV)。方法:20例受试者单次、交叉口服盐酸伐昔洛韦片300mg后,以喷昔洛韦为内标,用沉淀法去除蛋白,用HPLC-荧光法测定。结果:ACV在0．02～5μg·mL~(-1)的浓度范围内有良好的线性关系(r=0．999 95),最低检测浓度为0．02μg·mL~(-1)(S/N＞3),ACV的相对回收率为96．08%～97．28%,绝对回收率为69．62%～72．02%(n=5),日内精密度RSD为3．33%～6．12%,日间精密度为2．37%～6．81%。结论:本方法简便、灵敏、特异性强,可用于血浆中ACV的测定及人体药动学研究。     

盐酸丁螺环酮缓释片家兔体内血药浓度的测定

目的:建立盐酸丁螺环酮缓释片在家兔体内的血药浓度测定方法.方法:采用Nova-Pak C18柱(250mm×4.6mm,5μm),流动相为甲醇-乙腈-离子对试剂(10:50:40),检测波长为254nm.结果:缓释片中盐酸丁螺环酮在1～28ng·mL-1范围内呈良好的线性关系,r=0.999 5,平均回收率为98.45%,日内、日间精密度RSD均＜6%(n=6).结论:该测定方法准确、重现性好,简便、快速,适用于盐酸丁螺环酮缓释制剂研究的质量分析.     

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.