HPLC法同时测定氯霉素氢化可的松搽剂中氯霉素和氢化可的松的含量

目的 建立同时测定氯霉素氢化可的松搽剂中氯霉素和氢化可的松的含量测定方法.方法 采用高效液相色谱法.色谱柱为Agilent TC-C18,流动相为甲醇-水(60∶40),流速为1mL·min-1,检测波长为240nm.结果 氯霉素和氢化可的松浓度分别在19.06～762.36μg·mL-1和2.01～80.52μg·mL-1内线性关系良好,r分别为0.9997和0.9999;平均回收率分别为101.8%和102.0%,RSD分别为1.46%和1.24%(n=9).结论 该方法简单、快速、准确,可用于同时测定氯霉素氢化可的松搽剂中氯霉素和氢化可的松的含量.     

反相高效液相色谱法同时测定氯霉素氢化可的松滴耳液中氯霉素和氢化可的松含量的方法学研究

目的建立用反相高效液相色法同时测定氯霉素氢化可的松滴耳液中氯霉素和氢化可的松含量的方法.方法以Shim-pack VP-ODS柱(4.6mm×15cm,5μm)为色谱柱,甲醇-水(内含1.5%冰醋酸)(65:35)为流动相,流速1.0mL/min,进样量10μL.结果一次进样可同时测定两种组分的含量,氯霉素在154.5～1030.0μg/mL,氢化可的松在32.4～210.0μg/mL范围内,峰面积与其浓度均呈良好的线性关系,r值分别为0.999 9和0.999 6,日内精密度和日间精密度良好,平均回收率分别为100.1%,RSD=0.49%(n=9)和100.2%,RSD=0.42%(n=9)结论方法简单快速,结果准确,可作为该制剂的质控分析.     

HPLC法同时测定氯霉素氢化可的松滴耳液的含量

目的：建立高效液相色谱法同时测定氯霉素氢化可的松滴耳液含量。方法：色谱柱为Shim—packVP—ODSC18（150mm×4．6mln,5μm）;流动相为甲醇-水=65：35;氯霉素和氢化可的松检测波长分别选择为277nm和246nm;柱温为25oC,流速1．0ml·min-1。结果：氯霉素在1．41～45μg·ml-1,r=0．9997,氢化可的松在0．94～30μg·ml-1,r=0．9999范围内,线性关系良好。平均回收率氯霉素为100．5％,氢化可的松为100．7％。结论：方法快速灵敏、结果准确、重复性好,可用于该制剂的质量控制。     

氯霉素氢化可的松软膏的研制及质量控制

目的研制氯霉素氢化可的松软膏并建立质量控制标准。方法以FAPG软膏基质(脂肪醇和丙二醇)配制含1%氯霉素、0.5%氢化可的松软膏。采用HPLC法,以Agilent Eclipse XDB-C18(150 mm×4.6 mm,5μm)为色谱柱,甲醇-水(55∶45)为流动相,检测波长240 nm,流速0.9 ml.min-1,进样量10μl,对氯霉素氢化可的松软膏进行含量测定,室温下留样观察6个月,分别考察氯霉素、氢化可的松在软膏剂中的稳定性。结果氯霉素、氢化可的松保留时间分别为2.95、6.43 min;药物浓度与峰面积线性关系良好。氯霉素线性范围为50.18～401.44 mg.L-1,回归方程为C=0.075 93X+0.198 7,r=0.999 9(n=5),平均回收率为100.44%(n=9);氢化可的松线性范围为25.13～200.02 mg.L-1,回归方程为C=0.097 0X+0.357 0,r=0.999 9(n=5),平均回收率为99.86%(n=9)。氯霉素、氢化可的松在软膏剂中室温下保存6个月稳定。结论该制剂为溶液型软膏剂,氯霉素在该软膏剂中的稳定性较在乳膏剂中增加。制剂制备容易,控制方法快速、准确。     

HPLC法测定鼻腔洗液中盐酸溴乙新和氢化可的松含量

目的建立HPLC法测定鼻腔洗液中盐酸溴乙新和氢化可的松的含量。方法采用Kromasil C18（5μm,4．6×250mm）色谱柱;流动相为水（含0．025mmol·L^-1 KH2PO4、0．1％三乙胺、0．3％磷酸）：乙腈（60：40）：检测波长249nm;流速为1．0ml·min^-1;进样量20μl。结果盐酸溴乙新和氢化可的松的线性范围分别为1．6～12．8μg／ml（r=0．9996）,5～40μg/ml（r=0．9999）;平均加样回收率分别为：99．2％（RSD=0．5％）,99．4％（RSD=0．4％,n=6）;日内RSD分别为0．5％和0．6％（n=5）,日间RSD分别小于0．7％和0．6％（n=3）。结论该方法简便、准确,适合该制剂质量检验分析。     

RP—HPLC法测定醋酸氢化可的松乳膏中醋酸氢化可的松的含量

目的：建立了RP—HPLC法测定醋酸氢化可的松乳膏中醋酸氢化可的松的含量。方法：采用AgilentHC C18（4．6IDATI×250mm,5μm）色谱柱,乙腈-水（36：64）为流动相,检测波长254nm,流速1．0ml／min,柱温40℃。结果：醋酸氢化可的松在0．506～202．4μg／ml浓度范围内呈良好线性关系（r=0．99999）;醋酸氢化可的松乳膏的平均回收率为99．28％,RSD为0．42％（n=9）。结论：该方法快速、简便、准确、灵敏、重现性好,并能有效控制药品质量。     

双波长分光光度法测定氯霉素氢化可的松滴耳液中氢化可的松的含量

应用双波长分光光度法测定氯霉素氢化可的松滴耳液中氢化可的松含量。以乙醇、聚乙二醇_(400),丙二醇的混合液为溶剂,在波长247、309nm处进行测定。结果氢化可的松浓度在2～12μg·ml~(-1)之间,浓度与吸收度差值呈良好的线性关系。氢化可的松平均回收率为99.7％,RSD为0.7％(n=9)。该方法简便、快速、准确可靠     

氯霉素氢化可的松乳膏的制备及质量控制

目的:制备氯霉素氢化可的松乳膏并建立其质量控制方法。方法:以水包油基质制备乳膏;采用高效液相色谱法测定其中主药含量。结果:所制制剂各项检查均符合2005年版《中国药典》相关规定;氯霉素、氢化可的松线性范围分别为50.10～400.80(r=0.9997)、25.08～200.64μg.mL-1(r=0.9997);平均回收率分别为100.5%(RSD=2.1%)、100.4%(RSD=1.7%)。结论:本制剂制备工艺简便可行,质量稳定可控。     

氯霉素氢化可的松滴耳液的制备和质量控制及临床应用

目的：探讨氯霉素氢化可的松滴耳液的制备、质量控制及临床应用。方法：制备氯霉素氢化可的松滴耳液，采用紫外分光光度法测定氢化可的松的吸收度，观察临床效果。结果：氢化可的松在247nm处有最大吸收，氯霉素在247nm和309nm有等吸收点。平均回收率为100.25％，RSD为0．86％（n=9），临床总有效率99.00％。结论：该制剂处方合理，含量测定方法简便，疗效确切.     

氯霉素氢化可的松滴耳液含量测定方法的改进

摘 要 目的：建立氯霉素氢化可的松滴耳液中氯霉素和氢化可的松的含量测定方法。方法: 采用HPLC法,色谱柱：资生堂SPOLAR C18柱（250 mm ×4.6 mm,5 μm）;流动相：0.01 mol·L^-1庚烷磺酸钠缓冲溶液（称取磷酸二氢钾6.8 g,用0.01 mol·L^-1庚烷磺酸钠缓冲溶液溶解并稀释至1 000 ml,再加三乙胺5 ml,混匀,用磷酸调pH至2.5）-甲醇（40∶60）;柱温：30℃;流速：1.0 ml·min^-1;检测波长：245 nm;进样量：10 μl。结果: 氯霉素在50.26～753.84 μg·ml^-1（r=0.999 6）、氢化可的松在10.93～163.92 μg·ml^-1(r=1.000 0)范围内与峰面积有良好的线性关系。氯霉素的平均回收率为100.21%,RSD为0.48%（n=9）;氢化可的松的平均回收率为100.82%,RSD为0.37%（n=9）。结论:该方法专属性强、重复性好、精密度高,可作为氯霉素氢化可的松滴耳液的含量测定方法。     

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.

---

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.