HPLC法测定盐酸氨溴索注射液的含量和有关物质

目的建立高效液相色谱法测定盐酸氨溴索注射液的含量和有关物质的方法。方法采用Welchrom-C18(4.6 mm×200 mm,5μm)色谱柱,流动相为0.01 mol.L-1磷酸氢二铵溶液(用磷酸调pH值至7.0)-乙腈(50∶50),流速为1.0 mL.min-1,检测波长为248 nm。结果盐酸氨溴索在0.091～0.212 mg.mL-1范围内线性关系良好,相关系数r=0.999 9,平均回收率为99.60%(n=9)。结论采用高效液相色谱法测定盐酸氨溴索注射液的含量和有关物质,方法简便,结果准确可靠。     

HPLC法测定盐酸氨溴索分散片中盐酸氨溴索的含量

目的采用高效液相色谱法测定盐酸氨溴索分散片中盐酸氨溴索的含量。方法使用C18柱(大连依利特Hypersil ODS25μm,4.6mm×200mm),柱温:室温,流动相:以0.025mol.L-1磷酸二氢钾溶液(用磷酸调节pH值为3.0)∶乙腈(75∶25);流速1.0mL.min-1;检测波长244nm。结果采用高效液相色谱法测定盐酸氨溴索分散片中盐酸氨溴索的含量,线性范围为24.528～36.792μg.mL-1,r=0.9998;平均回收率分别为100.9%(RSD=0.5%)。结论用高效液相色谱法测定盐酸氨溴索分散片中盐酸氨溴索的含量,方法简便快速准确,能更好地控制产品质量。     

HPLC测定罗红霉素盐酸氨溴索分散片中的两种主药

目的 建立同时测定罗红霉素盐酸氨溴索分散片中罗红霉素和盐酸氨溴索的方法.方法 采用HPLC法,色谱柱为Alltech Alltima C18 (250 mm×4.6 mm,5 μm);柱温 35℃;流动相为5 mmol · L-1磷酸氢二氨(含5 mmol · L-1十二烷基硫酸钠和0.5%三乙胺,磷酸调pH5.0)-乙腈(58:42);流速 1.0 ml · min-1;检测波长210 nm;进样量20 μl.结果 罗红霉素的线性范围为1.5×10-3～4.5 mg · ml-1(r＝0.9999),日内RSD=0.3%,日间RSD为0.9%～1.5%,平均回收率为100.5%;盐酸氨溴索的线性范围为0.06～600 μg · ml-1(r＝0.9999),日内RSD=0.3%,日间RSD为0.9%～1.2%,平均回收率为100.8%(n=6).结论 所建方法简便快速,选择性好,精密度高,可控制罗红霉素盐酸氨溴索分散片的质量.     

高效液相色谱法测定盐酸氨溴索注射液中2种杂质的含量

目的采用高效液相色谱法测定盐酸氨溴索注射液中2种有关物质的含量。方法采用辛烷基硅烷键合硅胶Kromasil 100-5C8柱(250 mm×4.6 mm,5μm),以磷酸二氢铵缓冲液(取磷酸氢二铵2 g,溶于800m L水中,用磷酸调p H值至4.0,再加水稀释成1 000 m L)-甲醇(45:55)为流动相,流速为1.0 m L·min-1,检测波长分别为238、250 nm,柱温:30℃。结果杂质B反-4-(6,8-二溴-1,2,3,4-四氢喹唑啉-3-基)环己醇和杂质E 2-氨基-3,5-二溴苯甲醛的检出限分别为9.39 ng、3.70 ng,定量限分别为18.78 ng、11.10ng;线性范围分别为0.376¹8.8μg·m L-1(r=0.999 9)、0.38618.8μg·m L-1(r=0.999 9)、0.386⁷.72μg·m L-1(r=0.999 8),平均加样回收率均在99.8%7.72μg·m L-1(r=0.999 8),平均加样回收率均在99.8%¹00.1%,RSD均<0.5%。结论该方法测定盐酸氨溴索注射液中的有关物质方法简便、准确、专属性强,可用于盐酸氨溴索注射液中有关物质的质量控制。     

高效液相色谱法测定人血浆中氨溴索含量

目的:建立测定人血浆中氨溴索的高效液相色谱法。方法:色谱柱为ZORBAX Eclipse XDB-C18(4.6mm×150mm,5μm);保护柱为Eclipse XDB-C18(4.6mm×12.5mm,5μm);流动相为乙腈-磷酸氢二胺缓冲液(pH7.0)(45∶55);紫外检测波长242nm;流速1.0mL.min-1;柱温30℃;内标为盐酸地尔硫卓。结果:回归方程线性良好,方程:A=0.0021C 0.029 5,r=0.9999(n=5),线性范围为10~640μg.L-1,最低检测质量浓度为5μg.L-1。低、中、高(20,160,480μg.L-1)3种质量浓度的绝对回收率和相对回收率分别为90.6%,85.6%,91.8%和102.4%,91.8%,93.3%。日内、日间RSD均小于10%。结论:该方法适用于测定人血浆中氨溴索含量,结果准确、可靠。     

离子对-HPLC法测定盐酸倍他司汀注射液中药物与有关物质含量

目的用离子对HPLC法测定盐酸倍他司汀注射液中药物及有关物质含量。方法色谱柱:Diamonsil C18柱(200 mm×4.6 mm,5μm);流动相:甲醇10 mmol.L-1醋酸钠溶液(含5 mmol.L-1庚烷磺酸钠,体积分数为0.2%的三乙胺,用冰醋酸调pH至3.3)(25∶75),检测波长:261 nm,流速:1.0 mL.min-1,柱温:室温。结果盐酸倍他司汀质量浓度在1~250 mg.L-1内线性关系良好(r=0.999 9),平均回收率为99.8%,RSD=1.0%。盐酸倍他司汀的理论塔板数大于2 000,盐酸倍他司汀与其主要杂质分离度不低于1.5。结论适用于盐酸倍他司汀注射液中药物与有关物质的含量测定。     

反相高效液相色谱法测定盐酸多沙普仑注射液的含量

目的:建立盐酸多沙普仑注射液的HPLC含量测定及有关物质检查方法.方法:色谱柱为Diamonsil C18(4.6 mm×250mm,5μm,迪马公司),流动相为水-甲醇(30:70),流量为1mL·min-1,检测波长为225 nm,柱温为40℃.结果:多沙普仑在20～200 mg·L-1浓度范围内,与峰面积呈良好的相关性(r=0.999 5),平均回收率为99.7%(n=9),RSD=1.0%.结论:本法专属性强、灵敏度高、重现性好,结果准确,适用于盐酸多沙普仑注射液的质量控制.     

HPLC法测定盐酸法舒地尔注射液的含量

目的建立高效液相色谱法测定盐酸法舒地尔注射液含量的方法。方法采用Welch Ultimate XB-C8色谱柱(4.6 mm×250 mm,5μm),流动相为0.03 mol.L-1磷酸氢二铵溶液-乙腈=76:24(用磷酸调节pH值至4.5),检测波长为275 nm,流速为1.0 mL.min-1。结果盐酸法舒地尔在90.04～210.08μg.mL-1的浓度范围内线性关系(r=0.999 9)良好,平均回收率为99.87%,RSD为0.24%。结论本方法专属强、准确度高,可用于盐酸法舒地尔注射液的质量控制。     

紫外分光光度法测定盐酸普鲁卡因注射液的含量

目的建立紫外分光度法测定盐酸普鲁卡因注射液含量测定方法.方法采用紫外分光度法测定盐酸普鲁卡因注射液的含量,测定波长为(290±1)nm.结果线性范围为4～12 mg·L-1,盐酸普鲁卡因的平均回收率为99.7%,RSD=0.34%(n=3),r=0.9999(n=5).结论该法简便、快速、准确,可作为盐酸普鲁卡因注射液的含量测定方法.     

HPLC法测定盐酸溴己新注射液的含量

目的建立高效液相色谱法测定盐酸溴己新注射液的含量。方法色谱柱:Apollo C18柱(4.6mm×250mm,5μm),柱温:30℃;流动相:乙腈-0.05mol.L-1磷酸盐缓冲液(磷酸调节pH=3.0)(40∶60),流速:1.0mL.min-1,检测波长为249nm。结果盐酸溴己新在2.264~45.28μg.mL-1浓度范围内线性良好(r=0.9999,n=5),平均回收率为100.4%(RSD=0.15%,n=6)。结论本法快速、简便、准确,重复性好。     

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.

     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.