HPLC梯度洗脱法同时测定冠心苏合滴丸中5个成分的含量

目的 建立HPLC梯度洗脱法同时测定冠心苏合滴丸中的马兜铃酸Ⅰ、荭草苷、异荭草苷、牡荆苷和异牡荆苷含量。 方法 采用Diamonsil C₁₈色谱柱(250 mm×4.6 mm,5 μm),以甲醇(A)-0.5％冰醋酸溶液(B)为流动相,进行梯度洗脱,流速0.9mL.min_-1,柱温30℃,波长切换法检测(0～21 min,390 nm,马兜铃酸Ⅰ;21～60 min,338 nm,荭草苷、异荭草苷、牡荆苷和异牡荆苷);进样量为10 μL。 结果 马兜铃酸Ⅰ、荭草苷、异荭草苷、牡荆苷和异牡荆苷5个成分的线性范围分别为4.16～83.20 μg.mL_-1(r=0.9996)、6.35～127.00 μg.mL_-1(r=0.9998)、4.98～99.60 μg.mL_-1(r=0.9992)、14.33～286.60 μg.mL_-1(r=0.9997)、16.37～327.40 μg.mL_-1(r=0.9994);平均加样回收率及相应的RSD分别为98.26%(1.40%),99.23%(1.35%),97.90%(1.58%),96.97%(1.14%),99.11%(1.58%)。结论 本文建立的方法符合方法学验证要求,可用于冠心苏合滴丸中的5个指标性成分的同时定量测定。     

高效液相色谱法测定金莲花胶囊中3种黄酮苷含量

目的 建立金莲花胶囊中荭草苷、牡荆苷和槲皮素的含量测定方法.方法 采用高效液相色谱法,色谱柱为Alltima HP C18柱(250mm×4.6 mm,5μm),流动相为乙腈-1%冰醋酸溶液(15:85),流速为1.0 mL/min,检测波长为360 nm.结果 在上述色谱条件下,槲皮素、荭草苷、牡荆苷分别在2~16,8~64,5~40 μg/mL范围内与峰面积积分值线性关系良好,平均回收率分别为97.66%(RSD=2.06%),99.86%(RSD=1.89%),98.87%(RSD=2.64%).结论 该方法简便、准确、快速,可用于金莲花胶囊的质量控制.     

HPLC法测定导赤冲剂中异牡荆苷和异荭草苷的含量

目的 建立导赤冲剂中异牡荆苷和异荭草苷的含量测定方法.方法 采用高效液相色谱法,色谱柱为迪马C18柱,流动相为四氢呋喃-乙腈-0.2％磷酸水溶液(66∶ 22∶ 12),流速为1.0 mL?nin-1,柱温为35℃,检测波长为330 nm.结果 异荭草苷在0.82～4.08 μg范国内与峰面积积分值呈良好的线性关系(r=0.9990),平均加样回收率为96.4％,RSD为2.7％;异牡荆苷在0.79～3.96 μg范围内与峰面积积分值呈良好的线性关系(r=0.9999),平均加样回收率为98.8％,RSD为2.6％.结论 建立的含量测定方法简便、准确、灵敏,可用于导赤冲剂中异牡荆苷和异荭草苷的含量测定.     

荭草素和异荭草素、牡荆素和异牡荆素2对碳苷化合物的快速检测与鉴定

目的:建立利用超高效液相色谱-电喷雾电离质谱(UPLC-ESI/MS)快速检测和鉴定荭草素(orientin)和异荭草素(isoorientin)、牡荆素(vitexin)和异牡荆素(isovitexin)2对碳苷化合物的方法,并将其应用于荭草中上述2对碳苷化合物的分析鉴定。方法:采用BEH C18(2.1 mm×150 mm,1.7μm)色谱柱,柱温45℃,以甲醇(A)-0.1%甲酸水溶液(B)为流动相,梯度洗脱,流速0.3 mL.min-1;通过电喷雾电离源(ESI),考察了以正离子多反应监测(MRM)与不同能量下碰撞诱导解离(CID)对标准对照品中这2对碳苷化合物的检测和鉴定的可行性,利用所建立的方法筛选并鉴定了荭草粗提物中的这2对异构体。结果:建立了MRM筛选分析和CID快速鉴定荭草素和异荭草素、牡荆素和异牡荆素2对碳苷化合物的方法。应用这一方法,完成了荭草中这2对碳苷异构体的快速分析鉴定。结论:该方法简便、快速、可靠,可以用于荭草等含荭草素和异荭草素、牡荆素和异牡荆素2对异构体的药材及其相关产品中这些化合物的快速分析鉴定。     

高效液相色谱波长切换法测定不同产地龙胆饮片酒炙前后马钱苷酸与异荭草苷含量

目的建立同时测定龙胆饮片中活性成分马钱苷酸和异荭草苷含量的HPLC法,并对不同产地龙胆饮片酒炙前后马钱苷酸和异荭草苷的含量差异进行比较,根据含量水平对龙胆药材进行聚类分析。方法色谱柱:Welchrom C_(18)柱(4.6 mm×250 mm,5μm);流动相:0.04%磷酸溶液(A)-甲醇(B),梯度洗脱;流速:1.0 mL·min~(-1);检测波长:0～21 min,236 nm(马钱苷酸)、21～25 min,350 nm(异荭草苷);柱温:25℃;进样量:10μL;采用IBM SPSS statistics 24.0软件进行聚类分析。结果马钱苷酸、异荭草苷分别在8.0625～258μg·mL~(-1)(r=0.9998),0.402～12.85μg·mL~(-1)(r=0.9997)与峰面积线性关系良好,平均回收率分别为98.8%(RSD=0.94%)、98.2%(RSD=1.2%);聚类分析显示所测龙胆饮片大致分为两类。结论该方法简便准确,分离效果及重复性好,可为龙胆饮片的质量控制提供参考。不同产地龙胆饮片中马钱苷酸和异荭草苷含量存在显著差异,酒炙后两种成分含量大部分呈现下降趋势。     

UPLC-MS/MS同时测定Beagle犬血浆中原儿茶酸、异荭草素和野黄芩苷

目的建立Beagle犬血浆中同时测定原儿茶酸、异荭草素和野黄芩苷的超高效液相色谱-串联质谱分析方法。方法 Beagle犬单次股静脉注射88 mg.kg-1的注射用复方荭草(冻干粉针),分时取血处理。色谱采用Waters BEH C18反相柱,流动相为乙腈-水(含0.1%甲酸)梯度洗脱,质谱采用多反应离子监测(MRM)方式进行检测,用于定量分析的离子对分别为原儿茶酸m/z109.0→m/z152.8、异荭草素m/z449.2→m/z299.1、野黄芩苷m/z463.1→m/z287.1。结果原儿茶酸、异荭草素和野黄芩苷的线性范围分别为0.002～0.569、0.022～5.450和0.024～5.860 mg·L-1,方法的准确度,日内、日间精密度和稳定性均符合要求。结论该方法快速、灵敏、专属性强,可用于原儿茶酸、异荭草素和野黄芩苷的药代动力学研究。     

金莲花滴丸中荭草苷和牡荆苷的含量测定方法探讨

目的 探讨金莲花滴丸中荭草苷和牡荆苷的含量测定方法.方法 采用高效液相色谱法测定荭草苷和牡荆苷的含量,以Shimadzu VP-ODS(250×4.6 mm,5μm)色谱柱,0.5％冰醋酸水溶液-乙腈(88:12)为流动相,检测波长为340 nm,柱温35℃.结果 荭草苷在25.0～75.0μg/ml范围内呈良好的线性关系,平均回收率为99.9％,RSD为1.2％;牡荆苷在8.0～24.0μg/ml范围内呈良好的线性关系,平均回收率为100.5％,RSD为1.3％.结论 采用高效液相色谱法测定荭草苷和牡荆苷的含量准确可靠,重复性好,可作为金莲花滴丸的质量控制方法.     

金莲花多苷片中四种黄酮类化合物的含量测定

目的测定金莲花多苷片中四种黄酮类成分的含量。方法采用高效液相色谱法,以乙腈-0.2%磷酸溶液为流动相,流速为1.0 mL/min,柱温为室温,在360nm波长处,同时测定金莲花中四种黄酮类成分的含量。结果荭草素-2"-O-β-L-半乳糖苷、荭草苷、牡荆苷及槲皮素进样量分别在0.1976~1.9760μg、0.1010~1.0100μg、0.0604~0.6040μg、0.0608~0.6080μg范围内线性关系良好,平均回收率分别为99.17%、98.09%、99.15%、98.54%,RSD分别为1.05%、0.90%、0.54%。0.73%。结论本方法简单准确,重复性良好,适用于金莲花多苷片的含量测定。     

HPLC法测定不同产地紫果西番莲叶中荭草素与异荭草素含量

目的建立高效液相色谱法测定紫果西番莲叶中荭草素、异荭草素的含量,并比较不同产地紫果西番莲叶中荭草素及异荭草素的含量差异。方法 色谱柱为Inertsil C18(5μm,4.6 mm×250 mm);流动相为乙腈-0.1%磷酸水溶液(18∶82);检测波长:350 nm,流速1 ml/min,柱温30℃。结果异荭草素、荭草素检测浓度分别在0.015～0.150 mg/ml(r=0.999 8)0、.012～0.120 mg/ml(r=0.999 8)范围内线性关系良好,平均回收率分别为98.91%(RSD=1.28%)、99.08%(RSD=1.12%)。结论本方法简便、准确,可以作为紫果西番莲叶中荭草素和异荭草素含量测定的一种有效方法。     

HPLC法测定蒲葵药材中6种组分含量

目的:建立HPLC法同时测定蒲葵中荭草苷、异荭草苷、牡荆苷、异牡荆苷、异鼠李素-3-O-β-D-葡萄糖苷、苜蓿素含量,并比较不同产地不同部位蒲葵中6种组分的含量。方法:采用Agilent TC-C18(4.6 mm×250 mm,5μm)色谱柱;以甲醇(B)-0.05%醋酸溶液(A)为流动相,梯度洗脱(0～25 min,B:33%→45%;25～40 min,B:45%→80%;40～45 min,B:80%→95%;45～50 min,B:95%→95%;50～60 min,B:95%→33%);流速0.800 mL·min-1;检测波长340 nm,柱温30℃。结果:6个成分的检测范围分别为荭草苷:8.59～550.0μg·mL-1(r=0.9997)、异荭草苷:9.37～600.0μg·mL-1(r=0.9999)、牡荆苷:8.59～550.0μg·mL-1(r=0.9998)、异牡荆苷:8.59～550.0μg·mL-1(r=0.9995)、异鼠李素-3-O-β-D-葡萄糖苷:7.81～500.0μg·mL-1(r=0.9999),苜蓿素:8.59～550.0μg·mL-1(r=0.9999);平均回...     

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.