RP—HPLC同时测定菝葜药材中总槲皮素和山柰酚含量

目的:建立同时测定菝葜药材中槲皮素和山柰酚含量的反相高效液相色谱法。方法:色谱柱:Lichrospher C_(18)柱(250 mm×4.6 mm,5 μm),流动相:甲醇-0.5%磷酸水溶液(55:45),流速:1.0 mL·min~(-1),检测波长:365 nm。结果:槲皮素在2.97～29.7μg·mL~(-1)浓度范围内线性关系良好(r=0.9999),山柰酚在3.01—30.1μg·mL~(-1)浓度范围内线性关系良好(r=0.9999),方法回收率分别为98.9%和99.7%。结论:本方法简便、准确,灵敏度高,重复性好,可为评价菝葜药材质量提供依据。     

高效液相色谱法测定复方异维倍克气雾剂中异丙托溴铵和盐酸克仑特罗的含量

目的:建立高效液相色谱法测定复方异维倍克气雾剂中异丙托溴铵和盐酸克仑特罗含量。方法:采用反相高效液相色谱法。Intersil C_(18)分析色谱柱(4.6 mm×250 mm,5μm),流动相为乙腈-水(16:84;含0.4%三乙胺,磷酸调 pH 为3),流速1.5 mL·mL~(-1),检测波长205 nm。结果:异丙托溴铵和盐酸克仑特罗的理论板数分别为2400和3500。异丙托溴铵回归方程Y=128458X 58038,r=0.9999,线性范围18.20～182.0μg·mL~(-1);盐酸克仑特罗回归方程 Y=1251564X 10954,r=0.9995,线性范围9.200～46.00μg·mL~(-1)。异丙托溴铵平均回收率为97.4%(n=5),RSD 为2.2%;盐酸克仑特罗平均回收率为100.8%(n=5),RSD为1.9%。异丙托溴铵和盐酸克仑特罗最低检出浓度分别为0.2μg·mL~(-1)和0.03μg·mL~(-1)。结论:方法简便,结果准确。     

高效液相色谱-紫外检测法测定利奈唑胺在体外药效学模型的浓度

目的 建立高效液相色谱-紫外检测法测定利奈唑胺(抗菌药)在国产肉汤基质的药物浓度.方法 MH肉汤样品350 μL,加入15%高氯酸沉淀蛋白,离心后取上清液50μL进样测定.Venusil XBP C_8(4.6 mm×250 mm,5 μm)色谱柱,流动相为水-乙腈(80∶20),流量为1.5 mL·min~(-1),紫外检测波长251nm,室温;用高效液相色谱-紫外检测法测定利奈唑胺浓度.结果 线性范围0.5～40.0 μg·mL~(-1)(γ=0.9996),低、中、高浓度的绝对回收率均大于90%,相对回收率在96%～98%,日内、日间RSD分别小于2%和4%;最低检测浓度为0.5 μg·mL~(-1).结论 该方法准确可靠、操作简便、灵敏度高,适用于体外药效学模型中药物浓度测定.     

RP-HPLC法测定人体血浆中芬布芬的浓度

目的:建立测定人血浆中芬布芬浓度的高效液相色谱法。方法:采用 Diamonsil(钻石)ODS C_(18)色谱柱(250 mm×4.6mm,5μm),以甲醇-0.02 mol·L~(-1)磷酸二氢钾-乙腈(75:20:5)(用磷酸调节 pH 3.0)为流动相,流速为1.0 mL·min~(-1),检测波长285 nm。结果:芬布芬的线性范围为0.16～16.0μg·mL~(-1),定量限为0.16μg·mL~(-1),检测限为0.06μg·mL~(-1),平均回收率为(101.2±3.5)%,RSD 为1.8%,日内及日间精密度分别为1.7%和2.7%。结论:该方法简便、快速、准确,适用于临床上芬布芬的体内研究。     

HPLC法同时测定泌感颗粒中小檗碱和槲皮素的含量

目的:建立同时测定泌感颗粒中小檗碱和槲皮素含量的方法。方法:采用高效液相色谱法,色谱柱为 Diamonsil C_(18)柱(250 mm×4.6 mm,5μm),流动相为乙腈-0.05 mol·L~(-1)磷酸二氢钾溶液(27:73),流速为1.0 mL·min~(-1),检测波长为360nm。结果:小檗碱浓度在8.33～41.6μg·mL~(-1)范围内线性关系良好(r=0.9997),平均方法回收率(n=6)为98.6%;槲皮素浓度在4.08～20.4μg·mL~(-1)范围内线性关系良好(r=0.9998),平均方法回收率(n=6)为97.8%;结论:本法简便,准确度和重复性好,可用于泌感颗粒中小檗碱和槲皮素的同时测定。     

固相萃取HPLC测定人血浆中头孢西酮及在药动学研究中的应用

目的:建立反相高效液相色谱办法测定人血浆中头孢西酮浓度,并用于注射用头孢西酮钠人体药代动力学研究。方法:采用高效液相色谱紫外检测法,血浆中加入内标后经固相萃取,色谱柱为 Apollo C_(18)(5μm,250 mm×4.6 mm)。流动相为乙腈-0.02 mol·L~(-1)醋酸铵溶液(18∶82)(pH 5.0),流速1 mL·min~(-1),检测波长为278 nm。结果:本方法线性检测范围为0.5～250μg·mL~(-1),线性关系良好(r=0.9996);最低检测浓度为0.5μg·mL~(-1);方法绝对回收率为67.2%～84.0%,相对回收率为91.1%～102.1%;日内、日间 RSD 均小于8%。结论:本方法灵敏度高,操作简便,可用于人血浆中头孢西酮的浓度测定及临床药代动力学研究。     

高效液相色谱分离柱后化学发光法同时测定菟丝子中黄酮类成分

目的:建立高效液相色谱分离柱后化学发光法测定菟丝子中芦丁、山柰素、槲皮素和异鼠李素含量。方法:基于在氢氧化钠碱性介质中铁氰化钾可以直接氧化芦丁、山柰素、槲皮素和异鼠李素产生化学发光。色谱柱:Hypersil ODS(5μm,4.6 mm×150 mm),流动相:乙醇-乙腈-水-磷酸(21:22:55:2),流速:1mL·min~(-1),柱温:25℃。结果:芦丁、山柰素、槲皮素和异鼠李素浓度分别在0.2～5μg·mL~(-1)(r=0.9990),0.1～15μg·mL~(-1)(r=0.9991),0.1～100μg·mL~(-1)(r=0.9994),0.3～200μg·mL~(-1)(r=0.9998)范围内,与峰面积有良好的线性关系;检测限(S/N=3)分别为0.02,0.08,0.08,0.03μg·mL~(-1)。结论:水法简便、快速、有效,灵敏度高,首次用于菟丝子中黄酮类成分的测定,取得了很好的结果。     

高效液相色谱法测定氯霉素甲硝唑搽剂的含量

目的建立高效液相色谱法同时测定氯霉素甲硝唑搽剂中两组分含量。方法采用高效液相色谱法测定氯霉素和甲硝唑的含量。色谱条件为:Agilent Extend-C18色谱柱(4.6×250mm),流动相:甲醇-水-冰醋酸(45∶55∶0.1),流速1.0mL/m in,检测波长280nm,柱温30℃,进样量10μL。结果线性范围分别是:氯霉素49.82μg/mL~498.20μg/mL,r=0.9999;甲硝唑39.74μg/mL~397.40μg/mL,r=0.9999;平均回收率±RSD分别为99.42%±0.97%,99.83%±0.70%。结论本法简便,快速,准确,适用于该制剂中氯霉素和甲硝唑含量测定。     

HPLC法测定抗菌消炎胶囊中槲皮素和山柰素的含量

目的建立抗菌消炎胶囊中槲皮素和山柰素含量测定的高效液相色谱方法。方法色谱柱:Agilent Eclipse XDB-C18(250mm×4.6mm,5μm);流动相:甲醇-4mL·L~(-1)磷酸溶液(50∶50);柱温:30℃;流速:1.0mL·min~(-1);检测波长:360nm。结果槲皮素质量浓度在1.034~20.68μg·mL~(-1)范围内呈良好的线性关系(r=0.999 3),加样回收率为97.14%,RSD值为0.84%(n=6);山柰素质量浓度在2.061~41.22μg·mL~(-1)范围内呈良好的线性关系(r=0.999 1),加样回收率为98.05%,RSD值为0.59%(n=6)。结论该方法定量准确可靠,操作简便,灵敏度高,可用于抗菌消炎胶囊的质量控制。     

RP-HPLC法同时测定乙肝舒康胶囊中虎杖苷和二苯乙烯苷含量

目的:建立同时测定乙肝舒康胶囊中虎杖苷和二苯乙烯苷的高效液相色谱法。方法:采用 Hypersil C_(18)色谱柱(200 mm×4.6 mm,5μm),以乙情-水(20:80,v/v)为流动相,流速为1.0 mL·min~(-1),检测波长为320 nm。结果:虎杖苷和二苯乙烯苷的线性范围分别为1.5～30μg·mL~(-1)。(r=0.9993)和5～100μg·mL~(-1)(r=0.9999),平均回收率(n=9)分别为96.5%和100.9%。结论:本法简便,准确,重现性好。     

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.

     

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.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.