高效液相色谱法测定阿替洛尔片中阿替洛尔含量及其有关物质

目的:高效液相色谱法测定阿替洛尔片中阿替洛尔含量及其有关物质.方法:Inertsil ODS-3 C18 (5 μm,4.6 mm×150 mm)色谱柱,磷酸盐缓冲液-甲醇-辛烷磺酸钠(700∶300∶1.70)为流动相,检测波长:275 nm,流速:1.0 mL·min-1,柱温:36 ℃.结果:该方法能分离片剂中的阿替洛尔及其相关杂质,阿替洛尔在54.1～270.5 mg·L-1浓度范围内,线性良好,r=0.999 9;最低检测限21.6 ng.结论:HPLC法可作为阿替洛尔片的质量控制方法,简便快速,稳定可靠.     

高效液相色谱法测定苯磺酸氨氯地平片的含量及有关物质

目的:建立高效液相色谱法测定苯磺酸氨氯地平片的含量及有关物质的方法。方法:色谱柱为:Hypersil ODS2(4.6mm×250mm,5μm);柱温为25℃;检测波长为237nm;流动相为甲醇-0.03mol.L-1磷酸二氢钾水溶液(70∶30);流速为1mL.min-1。结果:制剂中其它成分不干扰测定,杂质峰和主峰达到有效分离。苯磺酸氨氯地平溶液在8.9~71.2mg.L-1范围内线性关系良好(r=0.999 9,n=5),平均回收率为99.9%,RSD为1.0%。结论:该方法适用于测定苯磺酸氨氯地平片的含量及其有关物质,方法简单,结果准确,专属性强。     

高效液相色谱法测定左卡尼汀原料中的有关物质

目的建立HPLC法测定左卡尼汀中有关物质。方法采用Thermo APS-2 HYPERSIL色谱柱(250 mm×4.6 mm,5μm),流动相为磷酸盐缓冲液(含磷酸二氢钾质量浓度为6.81 g·L~(-1),用氢氧化钠试液调节pH值至4.7)-乙腈(体积比为35∶65);检测波长为205 nm;柱温为30℃;流速为1m L·min~(-1)。结果左卡尼汀和杂质A得到有效分离,分离度>1.5,流动相不干扰测定;左卡尼汀的检出限和定量限分别为15μg·L~(-1)和50μg·L~(-1),左卡尼汀杂质A的检出限为0.19μg·L~(-1);杂质A在质量浓度0.95~47.5μg·L~(-1)内线性关系良好(r=0.999 3)。结论建立的方法可用于左卡尼汀原料中有关物质的测定。     

HPLC法测定乙胺吡嗪利福异烟片Ⅱ中利福平的有关物质

目的:建立乙胺吡嗪利福异烟片Ⅱ中利福平的有关物质的HPLC方法.方法:色谱柱为Kromasil C18(150 mm×4.6 mm,5μm),流动相为甲醇-磷酸盐缓冲液(55∶45),检测波长为254 nm,流速为1.0ml· min-1,柱温40℃,进样量为20μl.结果:共检测到6个杂质峰,各杂质峰与主峰分离度良好.结论:该方法专属性强,稳定性好,灵敏度高,可用于控制乙胺吡嗪利福异烟片Ⅱ的质量.     

HPLC法测定甲氧氯普胺片中甲氧氯普胺及有关物质的含量

目的建立测定甲氧氯普胺片中甲氧氯普胺及有关物质含量的方法。方法采用HPLC法。色谱柱为C18柱(250 mm×4.0 mm,5μm),流动相为乙腈-20 mmol.L-1磷酸溶液(体积比19∶81,用三乙胺调pH值至4.0),流速为1.0 mL.m in-1,检测波长为275 nm。结果在建立的色谱条件下,甲氧氯普胺与杂质能完全分离;甲氧氯普胺质量浓度在12.4~124 mg.L-1内与峰面积呈良好的线性关系,r=1.0000,平均回收率为100.5%(n=9);有关物质(按甲氧氯普胺计)的检出限为0.3ng。结论HPLC法可用于甲氧氯普胺片的质量控制。     

HPLC测定阿折地平及其制剂的含量和有关物质

目的测定阿折地平、阿折地平片及胶囊的含量和有关物质。方法采用HPLC法,用D iamonsilTMC18色谱柱(250 mm×4.6 mm,5μm);流动相为乙腈-10 mmol.L-1磷酸二氢铵溶液(三乙胺调pH6.5)(82:18);流速1.0 m l.m in-1;检测波长254nm;柱温30℃;进样20μl。结果阿折地平与其相邻杂质峰能完全分离;在16.84~336.80μg.m l-1范围内,其线性关系良好(r2=0.9999)。结论所用方法简便、准确、专属性好,可作为阿折地平及其片剂和胶囊剂的含量测定及有关物质的检查。     

HPLC法同时测定洛索洛芬钠片中的5个已知杂质

目的:对洛索洛芬钠片的有关物质检测方法进行优化,提高杂质分离度和检出率。方法:采用Intersil ODS-3(4.6 mm×250 mm, 5μm);流动相为0.01 mol·L^-1的磷酸二氢钾溶液(pH 4.5)-乙腈(85∶15)(A)和0.01 mol·L^-1的磷酸二氢钾溶液(pH 4.5)-乙腈(15∶85)(B),梯度洗脱,流速1.0 mL·min^-1;检测波长220 nm;柱温40℃;进样体积20μL。结果:洛索洛芬钠与相邻杂质以及5个已知杂质之间均达到的分离、洛索洛芬钠和5个已知杂质的浓度与峰面积之间线性关系(r>0.999 9)、精密度、准确度和耐用性均良好;洛索洛芬钠片3批自制制剂与3批参比制剂的杂质谱基本一致,各批样品均符合制订质量标准的规定。结论:本法可用于洛索洛芬钠片有关物质的质量控制。     

硫酸卡那霉素及注射液有关物质高温型及低温型蒸发光检测器方法建立及比对北大核心CSCD

目的:建立硫酸卡那霉素及注射液有关物质高温型及低温型蒸发光检测器方法并进行结果比对。方法:高温型蒸发光检测器方法为采用-Waters XSelect?HSS T3(5μm,4.6 mm×250 mm)色谱柱,以0.2 mol·L1三氟醋酸溶液为流动相,流速0.3 m L·min^(-1),柱温30℃;蒸发光散射检测器漂移管温度110℃,载气流量2.5 L·min^(-1)。低温型蒸发光检测器方法为采用Agilent ZORBAX SB-C18(5μm,4.6 mm×250 mm)色谱柱,以0.2 mol·L^(-1)三氟醋酸溶液-甲醇(98∶2)为流动相,流速0.3 m L·min^(-1),柱温30℃;蒸发光散射检测器漂移管温度65℃,喷雾器比率40%,压力0.207 MPa。结果:采用高温型蒸发光检测器,线性范围为0.003~0.12 mg·m L^(-1)(r=0.999 6),检测下限和定量下限分别为^(-1)0.031μg和0.062μg;采用低温型蒸发光检测器,线性范围为0.003~0.12 mg·m L(r=0.999 1),检测下限和定量下限分别为0.022μg和0.051μg。2种方法的专属性,流动相比例和色谱柱的耐用性均符合要求。4批硫酸卡那霉素和6批注射液的检测结果比对表明卡那霉素B的检测结果差异不大,其他单个杂质和杂质总量低温型检测器检测结果均高于高温型检测器。结论:本文建立的2种有关物质检测方法均适用于硫酸卡霉素及其注射液的有关物质检查,低温型检测器的最大杂质为相对保留时间约为0.85的未知杂质,高温型检测器的最大杂质也为主峰前杂质,但与其他杂质峰的未达到基线分离。对杂质的分离能力,低温型检测器更有优势。同时,低温型检测器杂质检出量和检出个数均优于高温型检测器,2种方法的建立为进一步制定合理限度进行有关物质控制以及杂质解析奠定了研究基础。     

RP-HPLC法测定丁酸氯维地平原料药中有关物质

目的建立测定丁酸氯维地平原料药中有关物质的RP-HPLC法。方法采用Welchrom C_(18)色谱柱(250 mm×4.6 mm,5μm);流动相为甲醇–环己烷–水(70∶0.5∶30);体积流量为1 m L/min;柱温为30℃;检测波长为240 nm;进样体积为20μL。结果丁酸氯维地平及其14种杂质能够达到良好的分离;丁酸氯维地平及其杂质I、III、IV、V的质量浓度与峰面积的线性关系良好;丁酸氯维地平及其14种杂质的检测限(S/N≥3)在0.57~3.13 ng。结论该方法简便准确、重复性好,专属性强,精密度高,可用于丁酸氯维地平原料药中有关物质的测定。     

RP-HPLC法测定枸橼酸托法替尼含量及有关物质

目的建立测定枸橼酸托法替尼含量及有关物质的RP-HPLC法。方法使用C18色谱柱(250 mm×4.6 mm,5μm),以乙腈-磷酸盐缓冲液(p H 7.0)为流动相(含量测定采用等度洗脱,体积比25∶75;有关物质测定采用梯度洗脱),流速1.0 m L·min~(-1),检测波长289 nm,柱温30℃。结果在含量测定色谱条件下,托法替尼在质量浓度10.0~60.0 mg·L~(-1)内呈良好线性关系(r=0.999 9),平均回收率为100.5%(n=9);在有关物质测定色谱条件下,托法替尼与各杂质能够得到良好的分离;杂质A~E在质量浓度0.16~1.6 mg·L~(-1),杂质F在质量浓度0.32~1.6 mg·L~(-1)内呈良好的线性关系,杂质A~F的r≥0.999 7。结论该方法可用于枸橼酸托法替尼的含量测定及有关物质的控制。     

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.