碘海醇中3-氯-1,2-丙二醇测定方法的改进

目的：建立毛细管柱GC法测定碘海醇中3-氯-1,2-丙二醇残留量的方法。方法：采用OV-1701石英毛细管柱（30m×0．32mm×1．0μm）,氢火焰离子化检测器,程序升温,进样口温度230℃,检测器温度250℃。结果：3-氯-1,2-丙二醇在4．982～398．6μg·mL^-1浓度范围内与峰面积呈良好的线性关系（r=0．9997,n=7）,加样回收率为80．0％（RSD=6．6％,n=15）;系统适用性溶液回收率应在60％-90％之间,分析了3批样品,第一批样品中未检出,第二批样品中含量为0．0030％,第三批样品中含量为0．0104％。结论：本法专属性强,灵敏度高,结果准确,可很好地控制碘海醇中3-氯-1,2-丙二醇的残留量。     

固相萃取-气相色谱-质谱法测定二羟丙茶碱中痕量3-氯-1,2-丙二醇

目的:建立二羟丙茶碱中痕量3-氯-1,2-丙二醇(3-MCPD)的气相色谱-质谱联用定性定量方法。方法:试样经饱和氯化钠提取,弗罗里硅土层析柱分离净化,旋转蒸发浓缩,三氟乙酸酐衍生后,进行气相色谱-质谱联用(SIM模式)检测。结果:3-氯-1,2-丙二醇在10～500μg·kg-1范围呈良好线性关系(r=0.9993,n=5),检出限为2.3μg·kg-1,三水平加标回收率均在96%以上,RSD在0.249%～1.151%之间。结论:该方法灵敏度高,重现性好,适用于药品中痕量3-氯-1,2-丙二醇的测定。     

LLE-GC-MS法同时测定甘磷酸胆碱中的缩水甘油和3-氯-1,2-丙二醇

目的 建立液液萃取-气相色谱-质谱法(LLE-GC-MS)同时测定甘磷酸胆碱原料药中的基因毒性杂质缩水甘油和3-氯-1,2-丙二醇。方法 采用酸性氯化钠溶液和酸性无水硫酸钠溶液分别处理甘磷酸胆碱原料药，经硅藻土柱净化、富集后用七氟丁酰基咪唑衍生，采用气相色谱-质谱法(SIM模式)进行检测，以D₅-3-氯-1,2丙二醇作为内标，通过双样本差减法计算样品中缩水甘油和3-氯-1,2-丙二醇的含量。结果 2种基因毒性杂质与内标物的峰面积比值在0.1～2 mg·L^-1浓度范围内呈线性相关，相关系数(r)均不小于0.999 2,样品的加样回收率为86.4%～103.3%(RSD<6.0%,n=9)。结论 该方法灵敏度高、专属性强，适用于甘磷酸胆碱原料药中缩水甘油和3-氯-1,2-丙二醇的测定。     

(R)-3-氯-1,2-丙二醇及镇咳药左羟丙哌嗪的合成

目的制备高光学纯度的（R）-3-氯-1，2-丙二醇，并以此为原料改进镇咳药左羟丙哌嗪的合成工艺。方法以自制手性Salen—CoⅢ催化剂水解外消旋环氧氯丙烷得高光学纯度的中间体（R）-3-氯-1，2-丙二醇，该中间体再与N-苯基哌嗪反应合成镇咳药左羟丙哌嗪。结果与结论以手性Salen-CoⅢ催化剂水解环氧氯丙烷得到的（R）-3-氯-1，2-丙二醇光学纯度为99％；以此为原料合成的左旋羟丙哌嗪光学纯度为99％以上，收率为56．3％。目标产物经核磁共振氢谱、质谱确证。     

3-氯-1,2-丙二醇在大鼠体内的毒代动力学

目的　为了全面了解 3 氯 1 ,2 丙二醇 ( 3 MCPD)的毒理作用性质。方法　采用毛细管气相色谱 质谱 (GC MS)联用法测定大鼠血液中 3 MCPD的含量。结果　一次性给大鼠ig 75和 3 0 0mg·kg-1的3 MCPD后 ,血药浓度 时间的动力学符合一级吸收一室模型 ,t1/ 2kα 分别是 ( 1 .61± 0 .1 6)和 ( 1 .0 3±0 .1 9)h ,t1/ 2kβ是 ( 3 .40± 1 .0 1 )和 ( 7.3 8± 2 .76)h,tp为 ( 3 .2 4±0 .2 6)和 ( 3 .3 3±0 .3 9)h ,cmax为 ( 3 1±9)和( 2 1 5± 3 2 )mg·L-1,Cl是 ( 0 .2 7± 0 .1 0 )和 ( 0 .1 0±0 .0 4)mg·kg-1·h-1,V为 ( 1 .3 1± 0 .5 0 )和 ( 1 .0 1±0 .0 5 )L·kg-1。结论　结果表明 3 MCPD经胃肠道吸收入血快 ,在动物体内分布广泛。     

辅料对X线造影剂碘海醇注射液稳定性的影响

目的:考察不同辅料对国产碘海醇(Iohexol)注射液稳定性的影响。方法:测定高温灭菌前后6组不同辅料的碘海醇注射液pH、碘离子浓度、含量变化。结果与结论:同时含三羟甲基氨基甲烷(Tris ,1 .2mg/ml)、乙二胺四乙酸二钠钙(EDTA-Na₂Ca ,0 .1mg/ml) 2种辅料时,碘海醇注射液最稳定。     

固相萃取-反相高效液相色谱法同时测定人血清中地西泮及氯硝西泮

目的 :建立一种快速、灵敏的同时测定人血清中地西泮与氯硝西泮的HPLC方法。方法 :血样经C18 SPE小柱萃取后 ,在BeckmanODS色谱柱上 ,以甲醇 水 (6 0∶40 )为流动相 ,流速 1 .0ml·min- 1,2 31nm检测。结果 :氯硝西泮、地西泮的保留时间分别为 4.5,7.4min ;线性范围分别为 0 .0 3～ 1 .0 0 ,0 .2 5～ 1 0 .0 0 μg·ml- 1;平均日内RSD分别为 2 .40 %,2 .30 %;平均日间RSD分别为 2 .6 2 %,2 .49%;平均回收率分别为 99.7%,99.5%,平均RSD分别为 3.2 8%,3.36 %。结论 :本方法可用于同时监测地西泮与氯硝西泮血药浓度。     

毛细管气相色谱法测定羟丙基-β-环糊精中的有机溶剂残留量

目的：建立毛细管气相色谱法测定羟丙基-β-环糊精中乙醇和1,2-丙二醇的残留量的方法。方法：色谱柱为DB-624石英毛细管柱,柱温采用程序升温,FID检测器,检测器温度为250℃,进样口温度为250℃,以二甲亚砜为溶剂。结果：乙醇、1,2-丙二醇的检测浓度的线性范围分别为0．1～5．0mg·ml^-1（r=0．9999）、0．1～5．0mg·ml^-1（r=0．9997）;平均回收率为分别为99．0％,98．2％,（RSD分别为1．9％,2．2％）;最低检出限分别为1．03,0．81ng;3批样品中2种有机溶剂残留量均符合《中国药典》要求。结论：本方法简单、准确、灵敏度高、重复性好,可用于该药物中有机溶剂残留量的测定。     

毛细管气相色谱法测定氯唑沙宗片含量

目的　测定氯唑沙宗片中氯唑沙宗含量。方法　采用毛细管气相色谱法,色谱柱:OV -I弹性石英毛细管柱(30m×0 . 2 5mm,0 . 1μm),汽化室温度:2 2 0℃,检测器温度:2 5 0℃;检测器:FID检测器;载气:氮气;流速:2 . 5ml·min-1,尾吹:2 0ml·min-1,分流比5∶1。结果　氯唑沙宗15～4 0 μg·ml-1(r =0 9998)范围内呈良好线性关系,平均回收率为10 0 . 2 %。结论　该方法测定氯唑沙宗含量准确、可靠,回收率高。     

HPLC法测定大鼠体内8-氯腺苷及其代谢物的浓度

采用高效液相色谱法测定大鼠体内 8-氯腺苷及其代谢物 8-氯肌苷和 8-氯腺嘌呤的浓度。试样用乙腈沉淀蛋白后 ,水层进样 ,采用 YWG- C18柱 ,以甲醇 - 1 %醋酸 (含 0 .1 %四丁基溴化铵 )为流动相 ,检测波长 2 63nm。8-氯腺苷及其代谢物分离良好 ,最低检测浓度 8-氯腺苷、8-氯肌苷和 8-氯腺嘌呤分别为 0 .1 0μg/ ml,0 .50μg/ml,0 .2 5μg/ ml,日内精密度和日间精密度均在 2 .3%～ 1 6.0 % ,三种化合物回收率为 70 %～ 99%     

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.