血浆中去甲右美沙芬和愈创木酚甘油醚的HPLC测定

建立了灵敏度高、选择性好、可同时测定人血浆中右美沙芬活性代谢物去甲右美沙芬及愈创木酚甘油醚的HPLC-荧光检测法.采用C8柱(4.6mm×250mm),流动相为乙腈-0.05mol/L磷酸二氢钾-二乙胺溶液-冰醋酸(15:85:0.2:2,用磷酸调至pH3.0),检测波长λex=280nm,λem=313nm.以盐酸曲马多为内标,血浆样品经液-液萃取后进样测定.方法的日内、日间RSD小于4.63%,回收率97.3%～102.6%.去甲右美沙芬及愈创木酚甘油醚的检测灵敏度分别为5.412和20ng/ml.经方法学验证,满足药物动力学研究的要求.     

氯诺昔康静脉镇痛配伍药物含量的高效液相色谱法测定

目的 建立应用高效液相色谱(HPLC)技术同时测定静脉镇痛液中盐酸氯胺酮、盐酸曲马多、丁溴东莨菪碱、氟哌利多、咪达唑仑与氯诺昔康含量的方法.方法 采用日本DL-C18(150mm×4.6mm,5 μm)色谱柱,乙腈-0.05 mol/L磷酸二氢钾水溶液(21:79)为流动相,流速为0.8 ml/min.结果 盐酸氯胺酮、盐酸曲马多、丁溴东莨菪碱、氟哌利多、咪达唑仑与氯诺昔康分别在40～400 mg/L,8～800 mg/L,0.5～100 mg/L,0.5～25 mg/L,4～80 mg/L与4～400 mg/L浓度范围与峰面积具有良好的线性关系;平均加样回收率分别为98.6%、101.1%、100.4%、99.5%、98.3%与99.8%;相对标准偏差分别为1.12%、0.67%、0.95%、1.23%、1.72%与0.78%.结论 本方法方便、快速、准确,可以作为盐酸氯胺酮、盐酸曲马多、丁溴东莨菪碱、氟哌利多、咪达唑仑与氯诺昔康配伍检测的方法.

Abstract：

Objective To establish a high performance liquid chromatography (HPLC) method for determination of ketamine, tramadol, butylbromide,droperidol,metamizole and lomoxicam in analgesic mixture samples. Methods The chromatographic separation was achieved on DL-C18 (150 mm x 4. 6 mm,5 μm) with the mobile phase consisting of acetonitile and 0.05 mol/L potassium dihydrogen phosphate solution (21:79) at a flow rate of 0.8 ml/min. Results The linearities were in the ranges of 40-400 mg/L for ketamine,8-800 mg/L for tramadol, 0.5-100 mg/L for butylbromide,0.5-25 mg/L for droperidol,4-80 mg/L for metamizole and 4-400 mg/L for lomoxicam. The average recovery was 98.6% , 101.1% , 100.4% , 99.5% , 98.3% and 99.8%, respectively. RSD was 1.12% , 0.67% ,0.95% , 1.23% , 1.72% and 0.78%. Conclusion The method is sensitive,rapid and accurate and suitable for compatible determination of ketamine, tramadol, butylbromide,droperidol, metamizole and lomoxicam in analgesic mixture samples.     

国产盐酸曲马多栓的人体药代动力学和相对生物利用度研究

随机交叉直肠给予12名健康男性受试者100 mg进口和国产盐酸曲马多栓.采用气相色谱法测定给药后不同时间的血浆药物浓度,研究国产盐酸曲马多栓在人体内的药代动力学和相对生物利用度.研究结果表明:进口和国产盐酸曲马多栓的药代动力学参数(均数±标准差):Tmax分别为2.6±1.0 和2.7±1.1 h;Cmax分别为384 ±67和392 ±71 μg·L-1;T1/2分别为8.7 ±2.5和8.9±2.6 h;Vd/F分别为4.2 ±1.2 和4.4±1.3 L·kg-1;CL/F分别为22.8±10.9和22.8±9.2 L·h-1;AUC0～48分别为4792±1576和4719±1589 μg·h·L-1.经配对t检验上述参数差异均无显著性意义.国产盐酸曲马多栓相对生物利用度F为98% ±10%;其90%的可信区间为93%～113% .结果提示国产盐酸曲马多栓和进口盐酸曲马多栓具有生物等效性.     

Beagle犬血浆中非索非那定和伪麻黄碱的LC-MS/MS测定

建立了LC-MS/MS法测定Beagle犬血浆中的盐酸非索非那定及盐酸伪麻黄碱.采用C18色谱柱,以5 mmol/L乙酸铵溶液-甲醇(35∶65)为流动相,盐酸曲马多为内标,采用多离子反应监测方式,监测离子对分别为m/z 502.3→466.3(非索非那定)、m/z 166.5→148.1(伪麻黄碱)和m/z 264.1→58.2(内标).盐酸非索非那定及盐酸伪麻黄碱分别在5～4 000ng/ml和5～2 000ng/ml范围内线性关系良好,批内、批间RSD均小于15%.     

止咳水中盐酸氯胺酮、氢溴酸右美沙芬及盐酸曲马多的HPLC-MS/MS筛查方法

目的 建立止咳水中盐酸氯胺酮、氢溴酸右美沙芬及盐酸曲马多的HPLC-MS/MS筛查方法.方法 采用Eclipse XDB C18色谱柱(4.6mm×50mm,5μm);流动相:乙腈-0.4%乙酸铵溶液(内含0.2%三乙胺,用冰醋酸调pH值至5.5)(35:65);流速:0.8ml/min (分流比1:4);柱温:35℃...     

复方盐酸曲马多片中盐酸曲马多血药浓度的测定

目的:通过采用高效液相色谱方法测定复方盐酸曲马多中盐酸曲马多的血药浓度.方法:采用C18色谱柱(10um,4.6mm×200mm),0.01mol/L磷酸二氢钾-乙腈-四氢呋喃(85:5:10)为流动相,流速为0.8mL.min,柱温20℃,检测波长为218nm-1.结果:盐酸曲马多浓度在25ng/mL(a)1600ng.mL-1范围内线性关系良好(r=0.9995),方法回收率为95%以上.结论:该方法简便且重复性好.     

盐酸曲马多与枸橼酸芬太尼在氯化钠注射液中的稳定性研究

目的考察盐酸曲马多与枸橼酸芬太尼注射液在0.9%氯化钠注射液中的配伍稳定性。方法在室温条件下,观察两药配伍后的外观及pH值变化,盐酸曲马多与枸橼酸芬太尼的含量测定采用SinoChrom ODS-BP色谱柱,以乙腈-0.05 mol/L磷酸二氢钾水溶液（25∶75）为流动相,流速为1.0 ml/min。结果配伍液中盐酸曲马多与枸橼酸芬太尼的含量均大于98%,72 h内外观与pH值均未见明显变化。结论在室温条件下,盐酸曲马多与枸橼酸芬太尼注射液在0.9%氯化钠注射液中72 h内保持稳定。     

高效液相色谱法测定人血清中盐酸曲马多浓度

目的:建立人血清中盐酸曲马多的高效液相色谱测定法.方法:采用固相萃取法预处理血清样品,分析柱为Symmetry C18柱(5 μm,250 mm×4.6 mm),流动相为pH2.5的0.025 mol·L-1 磷酸二氢钾缓冲液-乙腈(82∶18),流速为1.2 mL·min-1, 荧光检测波长为λex为276 nm,λem为310 nm,Gain:100,柱温为25℃.结果:盐酸曲马多的保留时间为7.8 min左右; 血药浓度线性范围为15～1000 μg·L-1(r=0.9999),最低检测浓度为10 μg·L-1 (S/N＞3),萃取回收率在70%以上(n=5),分析方法回收率在98%～101%(n=5),日内和日间RSD分别为1.30%～6.84%和1.51%～3.81%(n=5).结论:本法操作便捷,灵敏度和精密度高,重现性好,适于盐酸曲马多的药动学研究.     

盐酸曲马多分子印迹聚合物膜电极的制备及应用

介绍了盐酸曲马多分子印迹聚合物离子选择性电极的制备、特性及应用.该电极在1.0×10~(-6)～1.0×10~(-2)mol/L范围内表现Nernst响应,斜率为30.4mV/pc,检测限为6.3×10~(-7)mol/L,回收率为97%～101%.     

愈美分散片的HPLC测定

建立了HPLC法测定愈美分散片中愈创木酚甘油醚和氢溴酸右美沙芬的含量.采用ODS柱,流动相为乙腈-甲醇-0.01%三乙胺溶液(18:15:67,pH3.5),流速1.0ml/min,检测波长276nm.愈创木酚甘油醚和氢溴酸右美沙芬的线性范围分别为6～72μg/ml和4.2～51μg/ml,平均回收率分别为99.0%和102.6%,RSD分别为1.2%和1.5%.     

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.