毛细管气相色谱法测定替米沙坦中的有机溶剂残留量

目的:建立气相色谱法测定替米沙坦中残留有机溶剂甲醇、乙醇、丙酮、二氯甲烷、氯仿、乙二醇和二甲基甲酰胺。方法:以DB-624弹性石英毛细管柱为色谱柱(30m×0.53mm),载气为氮气,采用氢火焰离子化检测器,进样口温度为200℃,检测器温度为250℃。顶空进样法采用程序升温(50℃,保持15min,以30℃.min-1升至160℃,保持5min),进样量1.0mL。直接进样法柱温为100℃,进样量1.0μL。结果:3批样品中7种有机溶剂残留量均符合规定。结论:本方法可测定替米沙坦中的有机溶剂残留量,方法简单、准确。     

毛细管气相色谱法测定枸橼酸他莫昔芬原料药中有机溶剂的残留量

目的：建立毛细管气相色谱法测定枸橼酸他莫昔芬原料药中有机溶剂残留量的方法。方法：色谱柱：DB-624（30m×0．53mm×3μm）弹性石英毛细管柱；柱温采用程序升温：起始40℃，保持13min，20℃／min升至230℃，保持15min；氢火焰离子化检测器，载气：氮气，流速：3．0ml·min-1，进样口温度：140℃；检测器温度：250℃；分流比为5：1。结果：甲醇、丙酮、乙酸乙酯、四氢呋喃及甲苯浓度的线性均在各自浓度范围内，线性关系良好。平均回收率为：95．1％～98．1％。结论：方法操作简便、结果准确可靠，可以用于枸橼酸他莫昔芬原料药中有机溶剂残留的测定。     

毛细管气相色谱直接进样检测34种残留溶剂

目的：建立一种常用的气相色谱法分离检测ICH中规定的34种残留溶剂。方法：以DB-624弹性石英毛细管柱为色谱柱（75m×0．53mm×3．0μm），载气为氮气，采用氢火焰离子化检测器（FID），进样口温度为220℃，检测器温度为300℃，柱温采用程序升温（35℃保持18min；以5℃·min^-1升至45℃，保持8min；以5℃·min^-1升至80℃，保持3min；以5℃·min^-1升至150℃，保持2min；再以30℃·min^-1升至250℃，并保持5min），流速3mL·min^-1。以N-甲基吡咯烷酮为溶剂，进样体积为1μL。结果：34种有机溶剂均能得到很好的分离，分离度绝大多数均大于1．5。峰面积与浓度呈良好的线性关系，精密度良好。结论：本文气相色谱条件可用于常用的34种溶剂的分离与测定，方法简单准确。     

顶空毛细管气相色谱法测定胸腺五肽长效微球中的残留溶剂

目的：建立顶空毛细管气相色谱法，用于胸腺五肽长效微球残留溶剂的测定。方法：采用DB-624弹性石英毛细管柱（30m×0．32mm，1．8μm），载气为氮气，氢火焰离子化检测器，进样口及检测器温度均为250℃。柱温采用程序升温：初始温度为40℃，保持10min，以8℃·min^-1升至120℃，保持4min，再以40℃·min^-1升至200℃，保持2min；流速为1．0mL·min^-1。分流比为10：1，以二甲基亚砜为溶剂。结果：甲醇、乙醇、丙酮、乙腈、二氯甲烷、乙酸乙酯与四氢呋喃7种溶剂均得到了较好的分离；在各自浓度范围内均具有良好线性关系，测定精密度RSD均小于2％，标准加样回收率为97．6％-99．1％，RSD小于1．8％；制备的微球有机溶剂残留量符合中国药典限度要求。结论：方法准确可靠，可用于胸腺五肽长效微球中残留溶剂的测定。     

毛细管气相色谱法测定西沙必利中有机溶剂残留量

目的：建立测定西沙必利中有机溶剂残留量的方法。方法：采用毛细管气相色谱法测定，色谱柱为DB-624毛细管柱；程序升温，初始温度为40℃，维持6min后，以10℃·min^-1升温至200℃保持5min。结果：在确定的色谱条件下各组分能基线分离，线性关系良好；加样回收率为91．3％～103．5％。最低检测浓度为0．45～6μg·mL^-1。结论：该方法灵敏度和准确度均达到有机溶剂残留量检测的要求，可用于西沙必利中有机溶剂残留量的测定。     

顶空气相色谱法测定氢化可的松琥珀酸钠中N，N-二甲基甲酰胺的残留量

目的建立测定氢化可的松琥珀酸钠中有机溶剂N，N-二甲基甲酰胺（DMF）残留量的方法。方法采用顶空气相色谱法，色谱柱为DB-624毛细管色谱柱（30m×0．32mm，1．8μm），载气为氮气，分流比为10：1，以二甲基亚砜（DMSO）为溶剂，柱温85℃，保持10min，然后以35℃／min的速率升温至200℃，保持6min，进样口温度为220℃，氢火焰离子化检测器（FID）温度为250℃。结果DMF质量浓度在0．0567～0．5090mg／mL范围内与峰面积线性关系良好，r=0．99998（n=7），平均加样回收率为101．4％，DMF的最低检出限为0．0028％。结论顶空气相色谱法可用于测定氢化可的松琥珀酸钠中有机溶剂DMF的残留量。     

GC法同时测定五味子挥发油中α-蒎烯、β-蒎烯、柠檬烯和乙酸龙脑酯的含量

摘要目的：建立同时测定五昧子挥发油中α-蒎烯、β-蒎烯、柠檬烯和乙酸龙脑酯4种成分含量的气相色谱方法。方法：采用水蒸气蒸馏法进行挥发油的提取，采用Gc法对挥发油中α-蒎烯、β-蒎烯、柠檬烯和乙酸龙脑酯4种成分进行含量测定。气相色谱条件：DB-17石英毛细管色谱柱（30m×0．25mm×0．25μm）；氢火焰离子化检测器（FID）；进样口温度230℃；检测器温度250℃；柱温以50℃为起始温度，保持2min，以10℃·min^-1升温至130℃，保持5min；载气为氮气，流速为1．2mL·min^-1；进样方式为分流进样，分流比10：1；进样量为1μL。结果α-蒎烯、β-蒎烯、柠檬烯和乙酸龙脑酯进样浓度分别在0．02～0．21mg·mL^-1（r=0．9998），0．006～0．10mg·mL^-1（r=0．9993），0．006～0．16mg·mL^-1（r=0．9994），0．04～1．00mg·mL^-1（r=0．9993）范围内呈良好线性关系；平均回收率（n=3）分别为99．5％～101．6％，96．3％～101．9％，98．6％～100．4％，96．1％～96．8％。结论：方法简便快速，可用于五味子挥发油中α-蒎烯、β-蒎烯、柠檬烯和乙酸龙脑酯4种成分的含量测定。     

顶空气相色谱法测定反式帕罗醇中6种有机溶剂残留量

目的建立测定反式帕罗醇中6种有机溶剂残留量的方法。方法采用项空气相色谱法,色谱柱为DB-624毛细管柱（30m×530μm,3．0μm）,载气为氯气,分流比为5：1,以二甲基甲酰胺（DMF）为溶剂,程序升温,初始柱温为40℃,保持12min,然后以10℃／min的速率升温至160℃,保持3min,进样口温度为220℃,氢火焰离子化检测器（FID）温度为250℃。结果丙酮、异丙醇、石油醚、乙酸乙酯、甲苯和四氢呋喃6种有机溶剂均得到有效分离,回收率及线性关系皆良好。结论该方法灵敏度、准确性均达到有机溶荆残留量的检测要求,可用于测定反式帕罗醇中有机溶剂的残留量。     

顶空气相色谱法测定格列齐特中有机溶剂残留量

目的：建立顶空气相色谱法测定格列齐特中6种有机溶剂残留量的方法。方法：采用顶空气相色谱法，FID检测器，在毛细管色谱柱DB-624（30m×0．53m×3μm）上程序升温，载气为氮气，进样口温度200℃，检测器温度280℃。结果：6种有机溶剂完全分离，在所考察的浓度范围内具有良好线性，乙醇、乙酸乙酯、乙腈、四氢呋喃、甲苯、苯的最低检出浓度分别为0．258，0．098，0．207，0．036，0．045，0．048μg·mL^-。精密度RSD均小于4．0％，平均回收率为94％～105％。结论：本方法简便，结果准确可靠，重现性好，可用于多种残留溶剂的同时测定。     

气相色谱法测定阿立哌唑原料药中4种有机溶剂残留量

目的 建立阿立哌唑原料药中残留有机溶剂乙醇、乙腈、二氯甲烷、N,N-二甲基甲酰胺的气相色谱测定方法 .方法 采用AC-1毛细管色谱柱(30m×0.53mm×1.0μm);氮气为载气;初始柱温为40℃,保持3min后以40℃/min的速率升至160℃,保持2min;氢火焰离子化检测器温度为200℃;进样口温度为160℃;进样量为1μL.结果 阿立哌唑原料药中的4种有机溶剂完全分离,在所考察的浓度范围内均具有良好的线性关系,加样回收率在98.1%~99.0%范围内.3批阿立哌唑样品中均未检出4种有机溶剂.结论 该方法 准确、灵敏度高,适用于阿立哌唑原料药中有机溶剂残留量的测定.     

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.

     

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.