高效液相色谱法快速测定霉酚酸血药浓度

目的建立高效液相色谱法快速测定人血浆中霉酚酸药物浓度.方法色谱柱为Diamonsil C18(4.6 mm×250mm,5 μm);流动相为乙腈-10 mmol·L-1磷酸二氢钾溶液(pH=3.0)(5050);柱温25℃;流速1.5 ml·min-l;检测波长254 nm.结果本测定方法的线性范围为0.1～50 nag·L-1,r=0.999 8.平均回收率为(97.5±5.4)%,日内RSD不大于5.8%,日间RSD不大于7.2%.MPA的最低检测浓度为0.1 mg·L-1.结论本方法简单、快速、灵敏、重复性好,适用于MPA临床血药浓度监测及人体药动学研究.     

高效液相色谱法测定人血浆中格列本脲浓度

目的:建立测定人血浆中格列本脲浓度的高效液相色谱法.方法:格列本脲血浆样品在酸性条件下以二氯甲烷-正己烷(50:50)提取,以格列齐特为内标.Nova-pakC18柱(4.6 mm×250 mm,4μm),流动相为乙腈-0.03 mol·L-1磷酸二氢钾(pH 3.0)(44:56),流速1.2 mL·min-1,检测波长228 nm.结果:标准曲线线性范围25～600μg·L-1(r=0.9992),血浆中格列本脲最低检测限为15μg·L-1.平均提取回收率为(81.9±3.6)%,平均方法回收率为(101.1±6.8)%,日内RSD≤5.0%,日间RSD≤9.1%.结论:该方法具有良好的准确性、精密性和较高的灵敏度,适用于格列本脲的药动学研究及治疗药物浓度监测.     

高效液相色谱法测定脂平康中大黄酸、大黄素的含量

目的:建立高效液相色谱法测定脂平康中大黄酸、大黄素含量的检测方法.方法:采用高效液相色谱法,Hypersil C18柱(4.6 mm×250 mm,5 μm);流动相:甲醇-0.3%醋酸(87:13);检测波长:434 nm;流速:1.0 mL·min-1;柱温:25℃.结果:大黄酸在1.47～29.40)mg·L-1,大黄素在1.16～23.20 mg·L-1范围内呈良好线性关系;回收率:大黄酸为98.38%,大黄素为98.06%;RSD:大黄酸为1.80%,大黄素为1.07%.结论:本方法检测快速,定量准确,重现性好,可用于脂平康的含量测定.     

高效液相色谱法测定西罗莫司血药浓度

目的:建立快速测定人全血中西罗莫司浓度的高效液相色谱方法.方法:色谱柱为Zorbax Eclipse XDB C18(4.6mm×150mm,5μm);流动相为甲醇-乙腈-去离子水(50∶22∶28,v/v);流速1.2mL·min-1;紫外检测波长278nm;柱温50℃.结果:西罗莫司浓度测定的线性范围为2.5～50.0μg·L-1,最低检测浓度为2.0μg·L-1,平均回收率为103.2%,日内RSD小于5%,日间RSD小于4%.结论:本方法简便、快速,定量准确,可用于西罗莫司临床药动学研究,也可用于西罗莫司常规血药浓度监测.     

高效液相色谱法测定乳结消片中柚皮苷和黄芩苷的含量

目的建立乳结消片中柚皮苷和黄芩苷的含量测定方法.方法采用高效液相色谱法,色谱柱为VP-ODS C18柱(250 min×4.6 mm,5μm),流动相为乙腈-0.6%磷酸溶液(2872),流速为0.9 mL·min-1,检测波长282nm,柱温30℃;进样量20μL.结果柚皮苷在32.8～196.8 mg·L-1范围内,质量浓度与色谱峰面积呈良好的线性关系(r=0.999 9),平均加样回收率为98.95%,RSD为1.84%(n=6);黄芩苷在12.6-168 mg·L-1范围内,质量浓度与色谱峰面积呈良好的线性关系(r=0.999 9),平均加样回收率为100.94%,RSD为1.32%(n=6).精密度测定柚皮苷日内RSD≤1.18%,日间RSD≤1.24%;黄芩苷日内RSD≤1.25%,日间RSD≤1.75%.结论该方法简便易行,准确可靠,可用于乳结消片的质量控制.     

HPLC法测定围手术期患儿血浆中瑞芬太尼浓度

目的:建立高效液相色谱法测定围手术期患儿血浆瑞芬太尼浓度.方法:采用Hypersil CN柱(250 mm×4.6 mm,5μm);流动相为乙腈-0.02 mol·L-1磷酸二氢钾水溶液内含三乙胺0.02%(30:70);流速1.0 ml·min-1;检测波长210nm;进样量为20 μl.结果:标准曲线在1.0～100.0 μg·L-1 内线性关系良好(r=0.999 3).最低检测浓度为1.0μg·L-1.提取回收率(76.51±0.82)%.方法回收率99.66%～102.40%.日内和日间RSD均小于15%.2μg·L-1组靶控浓度与实测浓度基本一致.结论:本方法快速、准确、灵敏、专一性好,适用于临床瑞芬太尼血药浓度检测和药动学研究.     

高效液相色谱法测定妇科洗剂中苦参碱的含量

目的:建立高效液相色谱法测定妇科洗剂中苦参碱的含量.方法:色谱柱为Hypersil BDS C18(200 mm×4.6 mm,5 μm);流动相为乙腈-0.2 mol·L-1的磷酸二氢钾(含0.2%的三乙胺,用磷酸调pH值2.7)4∶96;检测波长为207 nm;柱温30℃;流速0.9 mL·min-1.结果:苦参碱在0.02～0.34 g·L-1范围内,线性关系良好(r=0.999 6),平均回收率为96.02%,RSD为2.2%.结论:该方法简单、快速、准确.     

人血浆中硫唑嘌呤中间代谢物6-巯嘌呤的高效液相色谱测定法

目的:建立人血浆中硫唑嘌呤中间代谢物6-巯嘌呤(6-mercaptopurine,6-MP)的高效液相色谱测定法.方法:取血浆200μL,以6-硫鸟嘌呤(6-TG)为内标,用70%高氯酸沉淀蛋白,6 mol·L-1氢氧化钠调节pH至中性后进样分析.色谱柱:Shimpack CLC-ODS(150 mm×6 mm,5 μm)柱;流动相:乙腈-水-醋酸(10:489:1);检测波长为323 nm.结果:本方法在2～200μg·L-1浓度范围内,线性关系良好(r=0.999 5),RSD为6.79%(n=10);高、中、低3个浓度质控样本的批内及批间RSD在1.3%～6.3%之间,回收率在99.1%～101.5%之间(n=10).结论:本方法简便、准确,能够满足临床研究需要.     

高效液相色谱法测定口腔溃疡糊剂中盐酸金霉素的含量

目的:建立HPLC法测定口腔溃疡糊剂中盐酸金霉素含量。方法:色谱柱为KF-C18柱(4.6 mm×250 mm,10μm);柱温:40℃;流动相为水-N,N二甲基甲酰胺-乙腈(68:27:5),含磷酸氢二钠0.006 3 mol·L-1和乙二胺四乙酸二钠0.01 mol·L-1,并以10 mol·L-1氢氧化钠溶液调节pH至8.5;检测波长为380 nm。结果:盐酸金霉素在10～100μg·ml-1的范围内线性关系良好,r=0.999 6,平均回收率为99.4%,RSD为1.4%。结论:本方法简便,快速,准确,可用于口腔溃疡糊剂的质量控制。     

高效液相色谱法测定复方维生素胶囊中维生素B6与叶酸的含量

目的:建立测定复方维生素胶囊中维生素B6和叶酸含量测定的色谱分析方法.方法:采用Hypersil ODS2色谱柱(4.6 mm× 200mm,5μm);以甲醇-0.05 mol·L-1磷酸二氢钾缓冲液(11:89,pH 5.4)为流动相;流速1.0 mL·min-1;检测波长280 nm处测定.结果:维生素B6与叶酸分别在15.9～142.8mg·L-1,0.372～2.976 mg·L-1范围内呈线性关系;r分别为1.000 0,0.999 8.平均回收率分别为99.95%(RSD为0.83%),100.14%(RSD为1.35%).结论:本法同时测定复方维生素胶囊中维生素B6和叶酸的含量,方法简便、准确.     

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.