注射用雷贝拉唑钠有关物质的HPLC法优化检测

为优化注射用雷贝拉唑钠有关物质HPLC检测条件,本实验采用岛津LC-10A高效液相色谱仪系统,Shimadzu CLC-ODS色谱柱,流速1.0 mL.min-1,柱温25℃,检测波长为286 nm,流动相采用(c)0.05 mol.L-1磷酸二氢钾缓冲溶液-甲醇-乙腈(50︰30︰20,1.0 mol.L-1氢氧化钾溶液调pH 7.0)对其进行检查。流动相(c)较流动相(a)、(b)而言,主成分峰与杂质峰分离效果佳,专属性强、灵敏度高,适用于注射用雷贝拉唑钠中有关物质的测定。     

HPLC梯度洗脱法检查甲睾酮喷雾剂中的有关物质

目的 建立检查甲睾酮喷雾剂中有关物质的方法.方法 采用HPLC梯度洗脱法,色谱柱为VP-C18柱(250 mm×4.6 m,5 μm);以甲醇-乙腈-水(33:22:45)为流动相A,乙腈为流动相B,梯度洗脱;检测波长241 nm;柱温35℃;流速1.0 ml·min-1.结果 在选定的色谱条件下,主成分与有关物质能完全分离,各杂质峰分离良好,最低检测限为0.06 ng.结论 所建方法专属性强、灵敏度高、重复性好,可用于检查甲睾酮喷雾剂的有关物质.     

盐酸艾咪朵尔相关物质的分离与含量测定

目的建立RP-HPLC法分离测定盐酸艾咪朵尔相关物质。方法色谱柱为Agilent TC-C18柱(150 mm×4.6 mm,5μm),柱温35℃,以乙腈-甲酸水溶液(甲酸-水体积比0.3∶100)为流动相进行梯度洗脱,流速为1.0 mL.m in-1,检测波长254 nm。结果确定了盐酸艾咪朵尔合成中可能引入的杂质A、B、C和盐酸艾咪朵尔的出峰位置,在盐酸艾咪朵尔原料中,杂质A、B、C的含量质量分数均小于0.1%。结论采用杂质外标对照法较质量分数1%主成分自身对照法更能直接反映盐酸艾咪朵尔中有关物质的情况。     

高效液相色谱-电喷雾检测器测定熊去氧胆酸的有关物质

目的:建立高效液相色谱-电喷雾检测器法测定熊去氧胆酸中的10个有关物质。方法:采用SHISEIDO Capcell PAK C₁₈ MGII(150 mm×4.6 mm, 5μm)色谱柱,以0.1%甲酸-甲醇-乙腈(30∶45∶25)为流动相A,乙腈为流动相B,梯度洗脱,流速1.0 mL·min^-1,柱温40℃,检测器温度35℃,采集频率5 Hz,过滤常数3.6 s。采用主成分自身对照法计算已知杂质和其它杂质的含量,并对建立的方法进行方法学验证。结果:熊去氧胆酸与各杂质分离度良好;熊去氧胆酸、杂质A、杂质B、杂质C、杂质E的质量浓度均在1.0～100.0μg·mL^-1范围内与峰面积呈良好的线性关系,定量限均为1.0μg·mL^-1,检测限均为0.5μg·mL^-1,杂质的平均回收率在99.3%～100.1%,RSD(n=9)不高于2.0%;供试品溶液在10℃条件下放置24 h内稳定;微调液相色谱参数后,对有关物质的检测结果无影响。3批样品有关物质结果显示,杂质A的含量均小于1.0%...     

HPLC测定盐酸替罗非班的含量和有关物质

目的 采用HPLC法测定盐酸替罗非班的含量及有关物质.方法 采用Venusil XBD C18色谱柱(250 mm×4.6 mm,5μm),流动相为0.01 mol·L-1磷酸二氢钾缓冲液(磷酸调pH2.3)-乙腈(72:28),流速1.0 mL· min-1,柱温35℃,检测波长227 nm.结果 主成分与各杂质峰的分离度良好,盐酸替罗非班10.0～ 100.0 μg· mL-1与峰面积有良好的线性关系(r=0.9999),平均回收率为99.4％,RSD=1.3％ (n =9),检测限和定量限分别为0.3、1.0 ng.结论 所用方法专属性强、灵敏度高,适用于盐酸替罗非班的含量和有关物质的测定.     

RP-HPLC法测定盐酸异丙嗪注射液中主药和有关物质的含量

目的:建立以反相高效液相色谱法测定盐酸异丙嗪注射液中主药和有关物质含量的方法。方法:色谱柱采用DiamonsilC18,以0.05mo·lL-1磷酸二氢铵(pH3.2)-乙腈(70∶30)为流动相,流速1.0mL·min-1,检测波长249nm,检测3批盐酸异丙嗪注射液样品中主药和有关物质含量。结果:盐酸异丙嗪检测浓度线性范围为5.07～101.32μg·mL-1(r=0.9995);平均回收率为100.3%(RSD=0.33%,n=6);有关物质各杂质与主药峰之间的分离度良好。盐酸异丙嗪检测限和定量限分别为20、80ng·mL-1,3批有关物质的含量分别为1.9%、1.7%、1.0%。结论:本法操作简便,灵敏度高,结果准确,可有效控制盐酸异丙嗪注射液的质量。     

HPLC法测定盐酸左旋咪唑中有关物质

目的:建立高效液相色谱法测定盐酸左旋咪唑中的有关物质.方法:色谱柱为Aichrombond C18(250 mm×4.6 mm,5 μm);流动相为0.5%磷酸二氢铵(用三乙胺调节pH至6.5)-乙腈(70:30);流速为1.0 ml·min-1;检测波长为215 nm;进样量为10 μl.结果:有关物质各杂质峰与主峰之间分离良好,杂质2,3-二氢-6-苯基咪唑[2,1-b]噻唑盐酸盐的线性范围为1.11～11.10 μg·ml-1(r=0.998 5),最低检测限为0.6 ng.结论:该方法专属性强、重复性好,可用于盐酸左旋咪唑的有关物质测定.     

高效液相色谱法测定复方辛伐他汀烟酸缓释片的有关物质

目的 建立复方辛伐他汀烟酸缓释片有关物质检查的HPLC方法.方法 采用C18柱,以乙腈-0.1%磷酸溶液(50∶50)为流动相A,0.1%磷酸的乙腈溶液为流动相B,梯度洗脱,对辛伐他汀的有关物质进行检测;以乙腈-0.05mol·L-1磷酸二氢钠溶液(磷酸调pH至2.5)(1∶99)为流动相,对烟酸进行检测.结果 在建立的色谱条件下,辛伐他汀、烟酸峰与其相关杂质峰均能完全分离.结论 本法简便、准确、专属性强,可用于本品的有关物质检查.     

HPLC法检测盐酸多奈哌齐片中有关物质含量

目的:建立以高效液相色谱法检测盐酸多奈哌齐片中有关物质含量的方法。方法:色谱柱为AlltimaTM C18,流动相为0.01mo·lL-1磷酸氢二钾溶液(含3%三乙胺,pH=4.3)-甲醇(60∶40),检测波长为271nm,柱温为35℃,流速为1.0mL·min-1;以主成分自身对照法计算有关物质含量。结果:该色谱条件下,主成分与有关物质能完全分离,各杂质峰分离良好,最低检测限为0.05ng,有关物质含量均为0.42%。结论:该方法专属性强、灵敏度高、重复性好,可用于该制剂中有关物质的检测。     

HPLC法测定盐酸普拉格雷有关物质的含量

目的建立高效液相色谱法测定盐酸普拉格雷原料药中有关物质。方法采用色谱柱为Cosmosil C18(250 mm×4.6 mm,5μm)柱;流动相为乙腈-磷酸盐缓冲溶液(p H值3.0,体积比为60∶40);流速为1.0 m L·min~(-1);检测波长为219 nm;进样量为10μL;柱温为30℃。结果杂质OHTP、杂质PFTP、杂质MFTP、杂质二酮、杂质OXTP、杂质CATP和盐酸普拉格雷的定量限分别为6.0×10-2、0.24、0.24、0.50、0.24、0.51和0.12 mg·L~(-1);检测限分别为20、80、80、170、80、170和40μg·L~(-1)。各杂质在考察的质量浓度范围内线性关系良好(r≥0.999 0),平均回收率分别为96.4%、97.7%、95.3%、96.7%、95.4%和95.4%(n=9)。结论该方法可用于盐酸普拉格雷有关物质的测定。     

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.     

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.     

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.