LC-MS/MS法测定氢溴酸东莨菪碱在大鼠体内的组织分布

目的:研究氢溴酸东莨菪碱在大鼠体内各组织的分布特点。方法:液相色谱分离采用C18(3.0 mm×100 mm,3.5μm)色谱柱,甲醇-2 mmol.L-1甲酸铵溶液(40∶60,甲酸调pH至3.52)为流动相,流速0.4 mL.min-1;质谱检测采用ESI离子源,正离子MRM方式检测。采取大鼠灌胃给药,运用液相色谱-质谱/质谱法测定氢溴酸东莨菪碱在大鼠各个组织中的药物浓度。结果:氢溴酸东莨菪碱在各个组织中的一定浓度范围内线性关系良好,各个组织中低、中、高浓度氢溴酸东莨菪碱的回收率及精密度均符合方法学要求。氢溴酸东莨菪碱在体内分布广泛,以脾、肝、肺中分布较高。结论:本方法简便、准确,灵敏度高,可用于氢溴酸东莨菪碱的体内分析研究。     

苍术中非法添加硫酸阿托品及氢溴酸东莨菪碱的检测方法

目的建立中药苍术中非法添加硫酸阿托品及氢溴酸东莨菪碱的定性定量检测方法。方法采用薄层色谱法定性、高效液相色谱法定量;色谱柱为phenomenex Luna C18柱（200 mm×4.6 mm,5μm）,流动相为0.07 mol/L磷酸钠溶液（含0.017 5 mol/L十二烷基硫酸钠,用磷酸调节pH至6.0-乙腈（70∶30）,流速为1.0 mL/min,柱温为30℃,检测波长为216 nm。结果硫酸阿托品及氢溴酸东莨菪碱进样量分别在1.97～9.85μg和2.03～10.15μg的范围内与峰面积积分值线性关系良好,平均加样回收率分别为99.67%和99.77%,RSD为0.12%和0.19%（n=6）。结论该方法简便、快速、准确,可用于检测苍术中非法添加的硫酸阿托品及氢溴酸东莨菪碱。     

离子对反相高效液相色谱法测定氢溴酸东莨菪碱注射液的含量

目的建立离子对反相高效液相色谱法测定氢溴酸东莨菪碱注射液的含量.方法流动相为甲醇-20mmol/L庚烷磺酸钠溶液-冰醋酸(50502),流速0.9mL/min,ZORBAX SB-C18色谱柱(4.6×250mm,5μm),检测波长225nm.结果线性范围为0.1～0.5mg/mL(r=0.999 8),平均回收率为101.15%,RSD为1.58%.结论本法简便、快速,结果准确,适用于氢溴酸东莨菪碱注射液的质量控制.     

复方氢溴酸东莨菪碱贴膏含量测定方法

目的：研究复方氢溴酸东莨菪碱贴膏中氢溴酸东莨菪碱含量测定方法.方法：采用加热回流提取复方氢溴酸东莨菪碱贴膏中的氢溴酸东莨菪碱,并用高效液相色谱法测定其含量.色谱柱：Agilent ZORBAX SB-C8柱（250 mm×4.6 mm,5 μm）,流动相：0.25%十二烷基硫酸钠溶液（用磷酸调节pH至2.5）-乙腈（60：40）,检测波长：210 nm,流速：1.0 ml·min^-1,进样量20 μl.结果：氢溴酸东莨菪碱浓度在11.24～224.80 μg·ml^-1范围内线性关系良好,r=0.999 9.平均加样回收率为98.22%,RSD为0.9%（n=6）.结论：所建含量测定方法简便准确,溶剂成本低,且较环保.     

高效液相色谱法测定胃痛宁片中天仙子浸膏含量

目的建立测定胃痛宁片中天仙子浸膏含量的高效液相色谱(HPLC)法。方法色谱柱为SunFire C18柱(250 mm×4.6 mm,5μm),流动相为乙腈(A)-0.1%磷酸溶液(B,含0.02%的三乙胺),梯度洗脱,流速为1.0 m L/min,柱温为35℃,检测波长为210 nm。结果氢溴酸东莨菪碱和硫酸阿托品与相邻杂质峰均可以完全分离;氢溴酸东莨菪碱和硫酸阿托品质量浓度分别在0.002146~0.10729 mg/m L和0.002071~0.10354 mg/m L范围内与峰面积线性关系良好,平均回收率分别为100.04%和98.91%,RSD分别为5.86%和5.54%(n=9)。结论该法可有效测定胃痛宁片中天仙子浸膏的含量,可为完善胃痛宁片质量标准提供参考。     

氢溴酸东茛菪碱的含量和降解产物的测定

目的:采用离子对色谱法测定氢溴酸东莨菪碱注射液的含量和降解产物.方法:以ODS柱为固定相,0.004%磷酸溶液(pH3.0)-乙腈(50:50)配制的0.008 mol·L-1十二烷基硫酸钠溶液为流动相,流速1.0 mL·min-1,用DAD检测器于波长210 m处测定.结果:氢溴酸东莨菪碱在5.868～293.4 mg·L-1范围内,与色谱峰峰面积呈良好线性关系,相关系数为0.9999,平均加样回收率为100.7%,RSD为0.8%(n=6).结论:对氢溴酸东莨菪碱的含量及降解产物进行研究表明,方法简便、快速,结果准确、专属性强.     

HPLC测定氢溴酸东茛菪碱的含量和有关物质

目的 采用HPLC法测定氢溴酸东莨菪碱的含量及有关物质.方法 色谱柱为Inertsil C8(150 mm×4.6 mm,5μm);流动相为乙腈-0.25%十二烷基硫酸钠溶液(磷酸调pH2.5)(4;6);检测波长210 nm.结果 氢溴酸东莨菪碱进样量0.8～12.4μg与峰面积的线性关系良好(r=0.9999);最低检测限为1.875 ng;最低定量限为6.008 ng.单一最大杂质为0.02%,有关物质总量为0.03%-0.07%.结论 所建方法 准确、简便、快速,适用于氢溴酸东莨菪碱的质量控制.     

HPLC法测定氢溴酸右美沙芬分散片中氢溴酸右美沙芬的含量

目的:建立高效液相色谱法测定氢溴酸右美沙芬分散片中氢溴酸右美沙芬的含量.方法:采用高效液相色谱法,色谱柱为TIAMHE○R C 18(200 mm×4.6 mm,5μm);流动相为甲烷磺酸溶液-乙腈(70:30);检测波长:280 nm,柱温:30℃;流速:1.0 ml/min.结果:氢溴酸右美沙芬在49.5~346.5μg/ml的浓度范围内,其浓度与峰面积呈良好线性关系(r=0.9999).平均回收率为100.05%,RSD为0.87%.结论:高效液相色谱法简便,快捷,精密度高,可用于氢溴酸右美沙芬分散片中氢溴酸右美沙芬含量测定.     

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%.     

高效液相色谱法测定丁溴东莨菪碱有关物质的研究

目的 :建立测定丁溴东莨菪碱有关物质的高效液相色谱法。方法 :采用WatersSymmetryC18色谱柱 (5μm ,3 9mm× 15 0mm) ,以 0 0 0 1mol·L-1盐酸 -甲醇 (185∶340 )配制的 0 0 0 8mol·L-1十二烷基硫酸钠溶液为流动相 ,用DAD检测器于 2 10nm波长处测定。结果 :丁溴东莨菪碱与其他莨菪碱峰完全分离 ,从而对主要的杂质氢溴酸东莨菪碱进行了限量检查。结论 :此法操作简便、快速、准确、具有量化的优点。     

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.