HPLC法测定沙纳唑的含量及其有关物质

目的:建立高效液相色谱法测定沙纳唑的含量及其有关物质。方法:采用 Kromasil KR 100 C_(18)色谱柱(4.6 mm×250mm,5μm)。流动相:甲醇-水-冰醋酸(200:800:3),流速:1 mL·min~(-1)。检测波长:248 nm。结果:HPLC法测定的线性范围为50～300μg·mL~(-1),r=0.9999,最低检测限为0.5 ng,本方法重复性和精密度良好(RSD<2％)。结论:采用HPLC法测定沙纳唑及其注射液的含量及有关物质,方法简便,结果准确。     

RP-HPLC法测定盐酸卡替洛尔口腔崩解片主药及有关物质的含量

目的:建立测定盐酸卡替洛尔口腔崩解片主药和有关物质含量的方法。方法:采用反相高效液相色谱法。色谱柱为Ulti-mate XB C18,以0.17%的Na2HPO4溶液(1mo·lL-1的H3PO4调节pH至3.0±0.05)-乙腈(85:15)为流动相,流速为1mL·min-1,检测波长为251nm,柱温为30℃。结果:盐酸卡替洛尔与有关物质及破坏后的降解成分可完全分离;盐酸卡替洛尔检测浓度线性范围为1.25～40.0μg·mL-1(r=0.9998);低、中、高3种浓度的回收率(n=3)分别为101.4%(RSD=0.12%)、101.3%(RSD=0.07%)、101.4%(RSD=0.03%);最低检测限为6.3ng,最低定量限为20.8ng。结论:该方法操作简便、快速准确、专属性强、灵敏度高,可用于盐酸卡替洛尔口腔崩解片主药及其有关物质的含量测定。     

HPLC法同时测定复方甲地孕酮注射液中主药的含量及有关物质

目的:建立测定复方甲地孕酮注射液中主药的含量及有关物质的方法。方法:采用高效液相色谱法。色谱柱为Diamon-sil C18柱,流动相为甲醇-水(70:30),流速为1.0mL·min-1,进样量为20μL,柱温为40℃,检测波长为280nm。结果:醋酸甲地孕酮和雌二醇的检测浓度分别在0.5～100.0、3.0～90.0μg·mL-1范围内与其峰面积积分值呈良好的线性关系(r=0.9999)。醋酸甲地孕酮定量限为17ng,最低检测限为5ng;雌二醇定量限为12ng,最低检测限为3.5ng。醋酸甲地孕酮和雌二醇的低、中、高平均回收率分别为102.0%、100.0%、99.9%和101.0%、101.7%、99.4%,RSD分别为0.37%、0.06%、0.10%和0.21%、0.17%、0.46%(n=9)。结论:该方法简便准确、重复性好,可用于复方甲地孕酮注射液的质量控制。     

HPLC法测定盐酸纳美芬的含量及其有关物质

目的:建立高效液相色谱法测定新药盐酸纳美芬及其注射剂的含量及其有关物质。方法:采用迪马公司C18钻石色谱柱(250 mm×4．6 mm,5μm);流动相:乙腈-0．05 mol·L-1的磷酸缓冲液(20:80),其中1 000 mL缓冲液中含有7．8 g磷酸二氢钠和2 mL的三乙胺,用85％的磷酸调节pH为4．2±0．02;流速:1．0 mL·min-1;检测波长为210 nm。结果:HPLC法测定的线性范围为21-126μg·mL-1,r=1．000,最低检测限为0．2 ng,本方法的重复性和精密度良好(RSD<2％),平均回收率为99．30％-99．42％。结论:采用HPLC法测定盐酸纳美芬及其注射液的含量和有关物质,方法简便,结果准确。     

HPLC法测定盐酸二氢埃托啡注射液的含量及有关物质

目的:采用高效液相色谱法测定盐酸二氢埃托啡的含量及其有关物质。方法:采用色谱柱为 Diamonsil ODS C_(18)柱(4.6mm×250mm,5μm,迪马公司),流动相为乙腈-0.02mol·L~(-1)KH_2PO_4(23:77),H_3PO_4调 pH 为3.5～4.0,流速为1.0 mL·min~(-1),检测波长为211 nm。结果:HPLC 法测定的线性范围为1.0～50μg·mL~(-1),r=0.9999,最低检测限为1ng,本方法的重复性和精密度良好(RSD<2%)。结论:采用 HPLC 法测定盐酸二氢埃托啡注射剂的含量及有关物质,方法简便,结果准确。     

HPLC法测定西格列羧的含量及有关物质

目的:建立抗2型糖尿病新药西格列羧的含量及有关物质的HPLC测定方法。方法:采用C18柱(150 mm×4．6 mm,5μm),流动相为甲醇-水-四氢呋喃-醋酸(35:35:30:0．5),检测波长为236 nm,流速为1．0 mL·min-1。结果:西格列羧在1.0-200μg·mL-1的浓度范围内,峰面积与浓度呈良好线性关系(r=1．0),回收率RSD小于0．2％,最低检测限为0．48 ng。结论:本方法专属、灵敏、可靠,可用于测定西格列羧的含量和有关物质。     

RP—HPLC法测定替米沙坦含量及有关物质

目的:采用反相高效液相色谱法测定替米沙坦的含量及有关物质。方法:色谱柱为Alltech公司Alltima C_(18)柱(150 mm×4.6 mm,5 μm),以乙腈-0.01 mol·L~(-1)醋酸铵缓冲液(60:40,用醋酸调节pH=6.0)为流动相,流速1.0 mL·min~(-1),检测波长分别为298 nm(含量测定)与255 nm(有关物质测定)。结果:替米沙坦在50-250μg·mL~(-1)范围内呈良好的线性关系,r=0.9999;最低检出限0.04 ng;日内精密度(RSD<0.5%)与日间精密度(RSD<0.5%)良好。结论:本方法简便、快速,结果准确、可靠。     

RP-HPLC法测定硝唑尼特含量及有关物质的方法学研究

目的:反相高效液相色谱法测定硝唑尼特的含量及其有关物质。方法:C18色谱柱(4.6 mm×150mm,填料:Hypersil,粒度:5μm),以乙腈-10 mmol·L-1甲酸(60:40)为流动相,流速0.8 mL·min-1,波长240 nm测定。结果:反相高效液相色谱法测定的线性范围为20.0-120.0μg·mL-1,相关系数为0.9998;最低检测限1.0 ng;样品溶液至少在24 h内稳定(RSD<1.0％);进样精密度(RSD<0.1％)良好。结论:本法简便、快速、准确,可用于硝唑尼特含量及其有关物质的测定。     

RP-HPLC测定麝香草酚的含量及有关物质

目的采用RP-HPLC测定麝香草酚的含量和有关物质。方法用C18色谱柱,流动相为水-甲醇(40∶60),流速为1.0 mL.min-1,检测波长276 nm。结果麝香草酚含量测定的线性范围为0.5014～2.0055 mg.mL-1(r=0.9999),RSD=0.20%;有关物质的线性范围为50.1～501.4μg.mL-1(r=0.9999);最低检测限为30 ng;最小定量限为98 ng。结论所用方法操作简便,结果准确可靠,可用于麝香草酚的含量测定和有关物质检查。     

HPLC法测定头孢泊肟酯分散片中有关物质的含量

目的:建立测定头孢泊肟酯分散片中有关物质含量的方法。方法:采用高效液相色谱法。色谱柱为ODS(C18)柱,流动相为水-甲醇(55:45),流速为2.0mL·min-1,检测波长为240nm,柱温为25℃,进样量为20μL。结果:头孢泊肟酯A、头孢泊肟酯B与杂质能完全分离;头孢泊肟酯A最小检测限为1.6ng,头孢泊肟酯B最小检测限为1.2ng,其有关物质含量均<4.0%。结论:该方法简便、准确,灵敏度高,专属性强,可用于头孢泊肟酯分散片有关物质含量的测定。     

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.     

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.