高效液相色谱法同时测定人血浆中对乙酰氨基酚、伪麻黄碱和咖啡因

目的:建立一种同时测定人血浆中对乙酰氨基酚、伪麻黄碱和咖啡因的高效液相色谱(HPIC)法,并用于含上述组分的复方制荆的人体药动学研究.方法:以荼碱为内标,血样经醋酸乙酯提取后,采用高效液相色谱紫外(HPLC_UV)法进行测定.色谱柱为Diamonsil C<,18>柱(4.6 mm x 150mm,5μm);流动相为甲醇-0.05 mo·L-1磷酸二氢钾(23:77,pH 2.4);流速1 mL·min-1.检测波长210 nm.结果:人血浆中对乙酰氨基酚、盐酸伪麻黄碱和咖啡因质量浓度测定的线性范围分别为0.12～11.52 mg·L-1,0.008～0.432mg·L-1和0.03～2.16mg·L-1;最低可定量质量浓度分别为0.12,0.008,0.03 mg·L-1;各组分日内、日间RSD均小于15%,方法回收率均大于88%.结论:该方法能快速可靠地同时测定人血浆中对乙酰氨基酚、伪麻黄碱和咖啡因的浓度.可用于含上述组分的复方制剂的人体药动学或生物等效性研究.     

HPLC法测定小儿氨酚匹林咖啡因片中四种成分的含量

目的:建立HPLC法同时测定小儿氨酚匹林咖啡因片中对乙酰氨基酚、咖啡因、阿司匹林及水杨酸的含量.方法:采用岛津ODS-VP色谱柱(4.6 mm×150 mm,5μm);以甲醇-0.01mol·L-1磷酸溶液(30:70)(用三乙胺调节pH值至3.1)为流动相;检测波长为220nm;流速为1.0 mL·min-1.结果:在建立的色谱条件下,对乙酰氨基酚、咖啡因、阿司匹林、水杨酸的线性范围分别为12.6～126 nag·L-1(r=0.999 9);3.0～30.0 rag·L-1(r=1.000 0);23.0～230 mg·L-1(r=0.999 8);0.115～6.9 mg·L-1(r=1.000 0).对乙酰氨基酚、咖啡因、阿司匹林的平均回收率分别为99,1%(RSD=1.32%,n=9);100.0%(RSD=0.57%,m=9);99.0%(RSD=1.09%,n=9).结论:本法简便、快捷,准确度高,专属性强,重现性好,可用于小儿氨酚匹林咖啡因片中对乙酰氨基酚、咖啡因、阿司匹林的含量测定及水杨酸的限度控制.     

HPLC测定复方氨酚苯海拉明片中对乙酰氨基酚和咖啡因含量

目的建立高效液相色谱法测定复方氨酚苯海拉明片中对乙酰氨基酚和咖啡因的含量。方法采用KromasilC18色谱柱(4.5 mm×150 mm,5μm),流动相为甲醇-水(30∶70),流速为1.0 mL.min-1,检测波长为280 nm,柱温为室温,进样体积为20μL。结果对乙酰氨基酚和咖啡因的线性范围分别为80~320 mg.L-1(r=0.999 7,n=7)和10~30 mg.L-1(r=0.999 7,n=5);高中低3种浓度的平均回收率分别为100.7%(RSD=0.69%),101.3%(RSD=0.53%),n=9。结论本方法简便、准确、灵敏、回收率高。     

高效液相色谱法同时测定小儿感冒冲剂中对乙酰氨基酚和咖啡因的含量

目的:建立同时测定小儿速效感冒冲剂中对乙酰氨基酚和咖啡因含量的高效液相色谱方法.方法:采用HypersilODS C18柱(5μm,250 mm×4.6 mm),流动相为甲醇∶水(30∶70),检测波长为280 nm,峰面积外标法.结果:对乙酰氨基酚在10.08～100.80μg·ml-1,咖啡因在0.592～5.920μg·ml-1浓度范围内线性关系良好;对乙酰氨基酚回收率为98.9%,RSD为0.58%(n=6),咖啡因回收率为100.15%,RSD为2.52%(n=6).结论:该方法具有操作简便、结果准确等优点.     

RP-HPLC测定复方氨酚烷胺胶囊中3种组分的含量

目的:采用高效液相色谱法测定复方氨酚烷胺胶囊中马来酸氟苯那敏、对乙酰氨基酚和咖啡因的含量.方法:使用ZORBAX Eclipse XDB-C18(4.6 mm×150 mm,5 μm),流动相为0.01 mol·L-1戊烷磺酸钠溶液(磷酸调节pH3.0)-甲醇(85∶15),柱温30℃,流速为1.0 mL·min-1,检测波长为216 nm.结果:马来酸氯苯那敏、对乙酰氨基酚和咖啡因的线性范围分别为:2.30～45.96 mg·L-1(r=0.999 7),32.37～647.32 mg·L-1(r=0.999 6),5.81～116.12 mg·L-1(r=0.999 7);平均回收率分别为99.6%,100.1%,99.9%,RSD分别为0.26%,0.60%,0.48%.结论:本法简便,快速经济,结果准确,重现性好,更有利于控制产品质量.     

高效液相色谱法同时测定血浆中的氯胺酮、咪唑西泮的浓度

目的:建立同时测定血浆中氯胺酮、咪唑西泮浓度的高效液相色谱法.方法:采用Diamosil C18色谱柱(4.6 mm×150 mm,5μm),以甲醇-磷酸盐缓冲液(65:35)为流动相,非那西丁为内标,流速为1.0 mL·min-1,在220 nm波长下定量测定氯胺酮、咪唑西泮血浆浓度.结果:氯胺酮在0.25～10.0 mg·L-1浓度范围内线性良好,r=0.9994,平均回收率为99.33%,日内、日间精密度RSD为0.66%～3.66%.咪唑西泮在25～1000μg·L-1浓度范围内线性良好,r=0.9995,平均回收率为101.46%,日内、日间精密度RSD为1.48%～3.36%.结论:本文HPLC法操作简单,快速,重现性好,准确可靠,适用于临床血药浓度监测及药动学研究.     

HPLC法同时测定阿咖酚胶囊中三种成分的含量

目的:建立同时测定阿咖酚胶囊中三种成分(对乙酰氨基酚、咖啡因、阿司匹林)的HPLC法.方法:色谱柱为Phenomenex C8柱(4.6 mm×250 mm,5μm),流动相为磷酸盐缓冲液(取0.01 mol·L-1磷酸二氢钾溶液,用磷酸调节pH至2.6±0.1)甲醇(65:35),流速为1.0 mL·min-1,检测波长为229 nm,柱温为30℃.结果:对乙酰氨基酚、咖啡因和阿司匹林的进样量分别在0.408 4～4.084,0.093 8～0.938和0.747 6～7.476μg范围内与峰面积呈良好线性关系,r分别为1.000 0,1.000 0,0.999 9(n=6),平均加样回收率分别为100.6%,100.5%和100.3%,RSD分别为0.8%,1.6%和1.2%(n=9).结论:本方法快速简便,准确可靠,可用于阿咖酚胶囊的质量控制.     

HPLC法同时测定人血浆中的对乙酰氨基酚、水杨酸和咖啡因的含量

目的建立同时测定人血浆中对乙酰氨基酚、水杨酸和咖啡因浓度的HPLC法,并将其应用于阿咖酚胶囊复方制剂的人体药动学研究。方法以甲醇-四氢呋喃-10 mmol.L-1醋酸盐缓冲液(含体积分数为0.1%的冰醋酸溶液)(体积比为23∶2∶77)为流动相,茶碱为内标,采用krom asil苯基柱分离,在237 nm处进行检测。结果血浆中对乙酰氨基酚、水杨酸和咖啡因测定方法的线性分别为0.203~16.2、0.503~80.4、0.103~8.24μg.L-1;方法的准确度?RE?分别为-4.2%~0.5%、-9.2%~-0.5%、-7.8%~1.9%;日内精密度?RSD?分别小于5.2%、6.5%、7.0%;日间精密度?RSD?分别小于8.1%、5.2%、6.2%。结论建立的HPLC方法可用于阿咖酚胶囊复方制剂的人体药动学研究。     

高效液相色谱法测定勃氏合剂中苯巴比妥钠和咖啡因含量

目的:用高效液相色谱法同时测定勃氏合剂中苯巴比妥钠和咖啡因含量.方法:色谱柱为C18柱(4.6 m×250 mm,5μm);流动相为甲醇-0.05 mol·L-1磷酸二氢钾溶液(每1 L加1.5 mL三乙胺,用磷酸调节pH至4.7)(50:50);流速:1 mL·min-1;检测波长:254 nm.结果:苯巴比妥钠和咖啡因分别在39.04～156.14mg·L-1和21.40～85.60 mg·L-1范围内线性关系良好;平均回收率分别为100.0%,99.2%(RSD为0.41%,0.45%).结论:本法简便、快速、准确,重现性好,适于该制剂的含量测定和质量控制.     

HPLC法同时测定感冒灵胶囊中三组分的含量

目的建立感冒灵胶囊的质量标准.方法采用 C18色谱柱,流动相为乙腈 0.03mol·L-1磷酸氢二铵(磷酸调 pH至3.1)(12∶88),进样量10μl,柱温为20℃,检测波长214nm,流速为1.0ml·min-1.结果对乙酰氨基酚、咖啡因、马来酸氯苯那敏分别在101.17~2023.40、2.00~40.09和2.05~40.93mg·L-1范围内线性关系良好,精密度 RSD分别为0.05%、0.09%、0.17%(n=8),平均回收率分别为100.4%、99.6%、99.6%.结论结果准确,方法重复性好,可作为该制剂的质量控制指标.     

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.