巴洛沙星有关物质测定方法的改进

目的:建立用高效液相色谱法(HPLC法)测定巴洛沙星降解物质的方法.方法:色谱柱为C18柱(250 mm×4.6 mm,5μm),流动相为乙腈-磷酸盐缓冲溶液(25:75);检测波长为295 nm.结果:HPLC法可测定巴洛沙星的有关物质.结论:HPLC法简单、快速、重现性好.     

用RP-HPLC法测定人血浆中巴洛沙星浓度并应用于治疗药物监测

目的:建立巴洛沙星血药浓度的RP-HPLC测定方法,并用于巴洛沙星片剂的药动学参数测定,为临床合理用药提供参考.方法:色谱柱为Diamonsil ODS C18柱(150 mm×4.6 mm,5μm),流动相为乙腈-水(含0.04 mol/L磷酸和0.4%三乙胺,pH=4.5):23,77,流速为1.0 mL/min,柱温35℃,检测波长294 nm.内标物为加替沙星.将该方法用于单剂量口服100 mg巴洛沙星片的主要药动学参数研究.结果:该方法的线性范围为0.05～5.00μg/mL(r=0.999 8),方法的日内及日间RSD＜10%.结论:该方法准确,快速、简便,可为临床评价药物治疗效果提供参考.     

RP-HPLC法测定普卢利沙星的含量及有关物质

目的:建立普卢利沙星的RP-HPLC含量测定及有关物质检测方法.方法:采用Agilent C18(250mm×4.6mm,5μm)色谱柱,0.5mol·L-1的磷酸二氢钾溶液(含0.5%的三乙胺,用磷酸调pH=3.0)-乙腈=30:70为流动相,检测波长280nm,流速0.8mL·min-1.结果:普卢利沙星在10～2 000μg·mL-1浓度范围内,峰面积与浓度呈良好线性关系(r=0.999 9),平均回收率99.86%,RSD=0.82%.结论:本法测定普卢利沙星的含量及有关物质,方法简便,快捷,结果准确,专属性好.     

高效液相色谱法检查巴洛沙星原料及片剂中有关物质

目的建立测定巴洛沙星原料及片剂中有关物质的高效液相色谱法。方法采用C18色谱柱(250×4.6mm,5μm);以0.05mol/L枸椽酸-乙腈(80∶20,用三乙胺调pH值为7.5)为流动相;检测波长264nm。结果巴洛沙星与其它杂质峰完全分离,从而对其有关物质进行限量检查。结论该法操作简便,结果准确,影响因素少。     

反相高效液相色谱法测定巴洛沙星片的含量及有关物质

目的:建立巴洛沙星片含量及有关物质测定的反相高效液相色谱方法.方法:色谱柱为DiamonsilTM C18(4.6 mm×250 mm,5 μm);流动相为乙腈-0.05 mol/L柠檬酸(用三乙胺调pH 4.0)(22:78),检测波长294 nm.结果:在0.52～83.2 μg/ml范围内,溶液浓度与峰面积呈良好的线性关系,平均回收率为99.6%,RSD为0.55%(n=9).结论:该方法简单、快速、准确,重现性及专属性好,可用于巴洛沙星片的质量控制.     

甲芬那酸片有关物质测定方法的研究

目的建立甲芬那酸片有关物质的测定方法。方法采用HPLC法。色谱柱:Phenomenex C18色谱柱(150mm×4.60mm,5μm);流动相:0.05mol·L-1磷酸二氢铵溶液(氨试液调节pH值为5.0)-乙腈-四氢呋喃(48∶40∶12);流速:1.0mL·min-1;检测波长:254nm。结果 2,3-二甲基苯胺的线性范围为0.79~12.60μg·mL-1,r=0.999 9,回收率为103.8%(n=9),RSD值为0.72%。结论该方法重复性好,结果准确,能有效控制甲芬那酸片中有关物质的含量。     

巴洛沙星片有关物质测定方法的研究

目的建立RP-HPLC法[1]测定巴洛沙星片的有关物质。方法采用Ecosil C18色谱柱（250 mm×4.6 mm,5μm）,0.05 mol/L磷酸二氢钾溶液（含0.2%三乙胺,用磷酸调节pH值为3.0）为流动相A,乙腈为流动相B,梯度洗脱,流速为1 mL/min,检测波长294 nm。结果采用主成分自身稀释方法测定,方法的专属性强,巴洛沙星在0.195 10~9.752 90μg/mL范围内呈线性,线性方程为A=53.009 7C＋1.508 4,相关系数为：r=0.999 9（n=5）。最低检测限为0.030 pg。结论结果方法准确可靠,重复性好,可用于巴洛沙星片有关物质的测定。     

HPLC法同时测定苦参碱葡萄糖注射液中苦参碱及有关物质的含量

目的:建立高效液相色谱法测定苦参碱葡萄糖注射液中苦参碱及有关物质的含量。方法:以 Lichospher 氨基柱(200mm×4.6mm,5μm)为分离柱;乙腈-0.02 mol·L~(-1)磷酸二氢钠(75:25)为流动相;流速:1.0mL·min~(-1);检测波长:210nm;进样量:20μL。结果:采用该方法线性范围为0.006～0.40mg·mL~(-1)(r=0.9990,n=6);稳定性试验 RSD 为0.43%(n=5);重复性试验 RSD 为0.52%(n=5);平均回收率为100.7%(n=9)。结论:本法简便、准确,重复性好,可用于苦参碱葡萄糖注射液的质量控制。     

RP—HPLC法测定羧胺三唑含量及有关物质

目的:采用反相高效液相色谱法测定羧胺三唑的含量及其有关物质。方法:采用Kromasil C_(18)色谱柱(4.6mm×250mm,5μm);以乙腈-水相(45∶55)为流动相;流速2.0mL·min~(-1);检测波长:262nm;柱温:室温;进样量:20μL。结果:反相高效液相色谱法测定的线性范围为12.5～200μg·mL~(-1);相关系数r=0.9999;日内精密度:RSD为0.38%(n=5);日间精密度:RSD为0.39%(n=5)。结论:本法简便快速、准确、专属性好。     

HPLC法测定异牡荆素磷脂复合物中的有关物质

目的建立高效液相色谱法测定异牡荆素磷脂复合物中有关物质含量的方法。方法采用Cosmosil 5C_(18)-AR-II色谱柱(250 mm×4.6 mm,5μm),流动相A:甲醇,流动相B:体积分数为0.2%的甲酸溶液,流速:1.0 mL·min~(-1),梯度洗脱,检测波长:272 nm,进样量:10μL,柱温:35℃。结果异牡荆素与有关物质A-C及未知杂质均能良好分离;各有关物质的质量浓度在0.5～12.5 mg·L~(-1)内线性关系良好,r≥0.999 3(n=6);精密度RSD不大于1.6%;回收率为96.1%～102.8%(RSD≤2.0%,n=9);经对3批样品测定,有关物质的质量分数均低于规定限度。结论该方法适用于异牡荆素磷脂复合物有关物质的检查。     

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.