HPLC法测定华山参滴丸中东莨菪碱、阿托品及东莨菪内酯的含量

目的:建立HPLC法测定华山参滴丸中东莨菪碱、阿托品及东莨菪内酯的含量。方法:采用资生堂CAPCELL-PAK C18(4.6 mm×250 mm,5μm)色谱柱,以乙腈-甲醇-磷酸氢二钠缓冲液(15∶4∶81)为流动相,流速1.0 mL·min-1,东莨菪碱、阿托品检测波长210 nm(0～15 min),东莨菪内酯检测波长为344 nm(15.1～30 min),柱温30℃。结果:东莨菪碱、阿托品及东莨菪内酯的线性范围分别为0.04～3.95,0.04～4.10,0.05～0.54μg(r=0.9999);平均回收率(n=6)分别为97.58%(RSD=1.3%),98.65%(RSD=1.3%),98.42%(RSD=1.8%)。结论:本文方法简便、准确,可以用于华山参滴丸中东莨菪碱、阿托品及东莨菪内酯的含量测定。     

HPLC-荧光检测法测定枸杞子和五子衍宗丸中东莨菪内酯的含量

目的采用高效液相色谱-荧光检测法(HPLC-FLD)测定枸杞子和五子衍宗丸中东莨菪内酯的含量。方法色谱条件:色谱柱为Agilent Extend-C18柱(4.6 mm×250 mm,5μm);流动相为乙腈-0.1%磷酸(18∶82);流速为1.0 m L·min?1;柱温30℃;荧光检测器激发波长343 nm,发射波长458 nm。结果东莨菪内酯在41.63~2 082 pg内线性关系良好(r=1),回归方程Y=44 095X–44 660,在枸杞子药材中平均回收率为101.1%,RSD为2.2%(n=9),在五子衍宗丸中平均回收率为102.6%,RSD为1.1%(n=9)。宁夏产的枸杞子东莨菪内酯含量高于其他产地。结论该方法快速、简便、灵敏,专属性、重复性良好,有助于评价枸杞子的道地性以及初步区分样品的来源,适用于枸杞子药材和五子衍宗丸中君药枸杞子的质量控制与评价。     

华山参中东莨菪内酯的含量测定方法研究

目的:建立高效液相色谱法测定华山参中东莨菪内酯含量的方法。方法:色谱柱:Agilent ODS C18柱(250 mm×4.6 mm,5μm),流动相:甲醇-0.3%磷酸溶液(30∶70),柱温:35℃,流速:1.0 mL.min-1,测定波长:344 nm。结果:东莨菪内酯的线性范围:9.84~1476.0 ng(r=0.99998);平均回收率在97.2%~100.7%,RSD为1.4%(n=6)。结论:本方法准确、可靠,重复性好,可用于华山参药材的质量控制。     

基于多成分定量分析结合薄层色谱检查的颠茄流浸膏质量评价

目的建立颠茄流浸膏中同时测定4种指标成分含量的方法,结合薄层色谱检查,为其质量评价提供依据。方法采用HPLC,色谱柱:Agilent Kromesil 100-5 C18柱(4.6 mm×250 mm,5μm),流动相为甲醇-0.05%甲酸溶液,梯度洗脱,流速1.0 mL·min^-1,柱温为30℃。采用薄层色谱法进行阿托品检查。结果 4种活性成分东莨菪苷在0.065 76~0.657 6μg(r=1.000 0)、山柰酚-3-O-半乳糖-(6→1)鼠李糖-7-O-葡萄糖苷在0.082 16~0.821 6μg(r=0.999 9)、东莨菪内酯在0.049 84~0.498 4μg(r=1.000 0)和芦丁在0.010 00~0.099 98μg(r=0.999 9)内,均呈良好线性关系;东莨菪苷、山柰酚-3-O-半乳糖-(6→1)鼠李糖-7-O-葡萄糖苷、东莨菪内酯和芦丁的加样回收率分别为100.6%,99.8%,99.9%和97.9%,RSD分别为1.4%,1.6%,1.4%和1.5%。部分批次指标成分含量低且检出硫酸阿托品。结论建立的含量测定方法灵敏度高,结果准确,适用于颠茄流浸膏的质量评价。     

反相高效液相色谱法测定风湿药酒中东莨菪内酯的含量

目的:建立反相高效液相色谱法(RP-HPLC)测定风湿药酒中东莨菪内酯的含量。方法:Hypersil C_(18)(150mm×4.6mm,5μm)色谱柱,流动相为甲醇-0.31％冰醋酸溶液(32:68),流速为1.0mL·min~(-1),检测波长为347nm。结果:东莨菪内酯在45～450mg·L~(-1)浓度范围内呈良好线性关系,回归方程Y=0.06299X+0.01777,r=0.9999(n=6),平均加样回收率为100.9％,RSD为1.59％(n=5)。结论:本方法简便,快速,灵敏,准确,重现性好,可以控制该制剂的质量。     

HPLC测定参附强心丸中东莨菪内酯和7-羟基香豆素含量

目的:建立HPLC法测定参附强心丸中东莨菪内酯和7-羟基香豆素含量的方法.方法:采用二极管阵列检测器,色谱柱为Phenomenex Luna C18(250mm×4.6mm,5μm);流动相为甲醇-0.5％冰乙酸水溶液,梯度洗脱;流速为1.0mL/min;检测波长为345nm.结果:东莨菪内酯线性范围为0.0760～0.3800μg(R2=0.999),平均回收率为104.54％,RSD为2.27％,重复性RSD为1.22％(n=6),精密度RSD为0.90％(n=6),稳定性RSD为0.91％;7-羟基香豆素线性范围为0.0300～0.1500μg(R2=0.999),平均回收率为102.51％,RSD为1.04％,重复性RSD为5.08％(n=6),精密度RSD为0.91％(n=6),稳定性RSD为0.91％.结论:本研究所建方法稳定、可靠,可作为该制剂的质量控制方法.     

中国药典2015年版颠茄酊中东莨菪内酯含量测定及特征图谱分析

目的 建立颠茄酊的HPLC特征图谱及东莨菪内酯的含量测定方法。方法 采用Welch XB-C₁₈(250 mm×4.6 mm,5 μm)色谱柱,流动相为甲醇-0.05%磷酸,梯度洗脱,流速：1.0 mL·min^-1;柱温：30 ℃;检测波长：344 nm。结果 建立了颠茄酊HPLC特征图谱,确定了6个共有峰,指认了其中3个共有峰的成分分别为山柰素-3-O-半乳糖-(6→1)鼠李糖-7-O-葡萄糖苷、东莨菪内酯和芦丁。东莨菪内酯进样量在11.18~670.5 ng(r=1.000 0)内线性关系良好,平均加样回收率为104.2%。结论 特征图谱结合东莨菪内酯的定量测定,能更好地控制颠茄酊的质量。     

胃肠宁胶囊定性定量方法研究

目的建立胃肠宁胶囊的质量控制方法。方法采用TLC法定性鉴别,HPLC法测定有效成分东莨菪内酯的含量。结果薄层色谱鉴别中,供试品色谱中,在与对照品、对照药材色谱相应的位置上,显相同颜色的斑点。东莨菪内酯在21.40~214.0μg·m L-1内与峰面积呈良好的线性关系(r=0.999 5),平均回收率为100.4%,RSD为1.7%。结论所建方法准确可靠、灵敏度高、专属性强,可有效控制胃肠宁胶囊的质量。     

HPLC法同时测定无梗五加果中东莨菪内酯和异嗪皮啶的含量

目的建立同时测定无梗五加(Acanthopanax sessiliflorus(Rupr.et Maxim.)Seem.)果中东莨菪内酯和异嗪皮啶含量的HPLC法。方法采用Zirchrom Kromasil ODS C18(4.6 mm×200 mm,5μm)色谱柱,流动相为乙腈甲醇水冰醋酸(体积比为13∶1∶86∶1),流速为1.0 mL.min-1,柱温为室温,检测波长为344 nm。结果东莨菪内酯和异嗪皮啶分别在0.975~7.80 mg.L-1和0.360~2.88 mg.L-1内质量浓度与峰面积呈良好的线性关系,回归方程分别为A=2.150×104ρ-2.964×102(r=0.999 1)和A=1.776×104ρ-1.947×103(r=0.999 7),平均回收率分别为101.2%和98.8%,测得样品中东莨菪内酯和异嗪皮啶的含量分别为30.5μg.g-1(RSD=1.7%)和7.90μg.g-1(RSD=2.4%)。结论方法准确、可靠,可为无梗五加果的质量控制提供参考依据。     

RP-HPLC法测定清肺合剂中东莨菪内酯的含量

目的:建立以反相高效液相色谱法测定清肺合剂中东莨菪内酯含量的方法。方法:色谱柱为C18(250mm×4.6mm,5μm),流动相为甲醇-0.5%醋酸(40∶60),检测波长为345nm,流速为1.0mL·min-1。结果:东莨菪内酯进样量在0.04～0.80μg范围内与峰面积积分值呈良好线性关系(r=0.9999);平均回收率为98.6%,RSD=1.35%(n=6)。结论:本方法方便易行、结果准确、重复性好,可用于清肺合剂的质量控制。     

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.