HPLC法测定美司钠原料中的有关物质

摘 要 目的：建立HPLC法测定美司钠原料中的有关物质。 方法: 采用C18柱（250 mm×4.6 mm,5 μm）;以甲醇 磷酸盐缓冲液（取磷酸二氢钾2.94 g、磷酸氢二钾2.94 g、四丁基硫酸氢铵2.6 g溶于660 ml水中,用磷酸调pH 2.3）（34∶66）为流动相;流速为1.0 ml·min-1;检测波长为235 nm。 结果: 美司钠与各杂质及强制破坏产物能完全分离;美司钠及杂质A、B、D、F分别在41.03～4 103.00 μg ·ml-1（r=1.000 0）、0.53～53.44 μg ·ml-1（r=1.000 0）、0.43～42.88 μg ·ml-1（r=1.000 0）、30.80～308.00 μg ·ml-1（r=1.000 0）、0.422 4～42.24 μg ·ml-1（r=1.000 0）范围内线性关系良好;各杂质加样回收率在97.8%～101.4%之间;进样精密度和重复性均符合规定;其中杂质A、B、F的相对校正因子分别为0.03,0.01,0.01。 结论: 建立的方法可用于美司钠原料有关物质的质量控制。     

吉西他滨相关血小板减少对晚期非小细胞肺癌患者生存时间的影响

摘 要 目的：探索吉西他滨相关血小板减少对晚期非小细胞肺癌（NSCLC）患者生存的影响。方法: 回顾性分析我院2011年1～12月接受吉西他滨化疗的晚期NSCLC住院患者,根据吉西他滨首次化疗后血小板计数（Plt)最低值分为Plt＞50×109·L-1组（43例）和Plt<50×109·L-1组（24例）。查阅电子病历提取相关资料,并随访生存时间。比较两组相关指标并进行COX多因素分析。结果:共入选病例67例。两组间除病理类型外,性别、年龄、化疗周期等差异均无统计学意义（P＞0.05）;Plt＞50×109·L-1组中位生存时间显著高于Plt<50×109·L-1组（P＜0.05）。结论:吉西他滨引起的重度Plt减少（Ⅲ度/Ⅳ度）会影响晚期NSCLC患者的生存时间,临床用药应积极做好Plt减少的预防和治疗。     

HPLC法同时测定参莲胶囊中7种生物碱成分的含量

摘 要 目的：建立RP HPLC双波长法同时测定参莲胶囊中氧化苦参碱、槐定碱、氧化槐果碱、苦参碱、槐果碱、粉防己碱、防己诺林碱7种生物碱含量。 方法: 采用Venusil XBP NH2（250 mm×4.6 mm,5 μm）色谱柱,以乙腈 0.01%醋酸铵水溶液为流动相梯度洗脱,流速为1.0 ml·min-1,检测波长为210 nm、280 nm。 结果: 氧化苦参碱、槐定碱、氧化槐果碱、苦参碱、槐果碱、粉防己碱、防己诺林碱线性范围分别为32.07～513.07 μg·ml-1（r=0.998 8）、37.90～606.40 μg·ml-1（r=0.999 2）、23.07～369.07 μg·ml-1（r=0.999 2）、52.37～837.87 μg·ml-1（r=0.999 7）、17.63～282.13 μg·ml-1（r=0.999 1）、5.30～84.80 μg·ml-1（r=0.999 5）、8.87～141.87 μg·ml-1（r=0.999 7）;平均加样回收率（n=9）为100.16%~102.84%（RSD≤2.0%）。5批样品中氧化苦参碱、槐定碱、氧化槐果碱、苦参碱、槐果碱、粉防己碱、防己诺林碱含量依次为9.18~9.69 mg·g-1、9.35~11.74 mg·g-1、6.73~7.09 mg·g-1、15.17~15.96 mg·g-1、5.03~5.33 mg·g-1、1.23~1.97 mg·g-1、2.48~2.74 mg·g-1。 结论: 所建立的多成分分析方法可用于参莲胶囊中7个生物碱成分的含量测定。     

复方枇杷喷托维林颗粒中吗啡的鉴别和含量测定

摘 要 目的：建立复方枇杷喷托维林颗粒中吗啡的鉴别和含量测定方法。方法: 采用薄层色谱对吗啡进行定性鉴别;采用高效液相法测定吗啡含量,使用Diamonsil plus C18（250 mm×4.6 mm,5 μm）色谱柱;流动相为乙腈 0.05 mol·L-1磷酸二氢钾 0.002 5 mol·L-1 庚烷磺酸钠（10 ∶〖KG-*4〗45 ∶〖KG-*4〗45）;流速1.0 ml·min-1;检测波长：220 nm。结果: 薄层鉴别斑点清晰,阴性对照无干扰。在选定的色谱条件下,吗啡在5.07～15.21μg·ml-1的质量浓度范围内线性关系良好(r=0.999 2),平均加样回收率为98.7%, RSD=1.9%（n=6）。结论: 本方法简便、准确,可用于该制剂中吗啡的质量控制。     

HPLC法测定米诺地尔洗剂含量及温度对含量影响的考察

摘 要 目的：建立高效液相色谱法同时测定化瘀祛斑胶囊中芍药苷、黄芩苷和黄芩素的含量。方法: 色谱柱为Agilent Zorbax SB C18柱（150 mm×4.6 mm,5 μm）;流动相为甲醇 0.1%磷酸溶液,梯度洗脱;流速为1.0 ml·min-1;检测波长为230 nm（0~15 min）,277 nm（15~45 min）;柱温为25℃;进样量为10 μl。结果: 芍药苷、黄芩苷和黄芩素的线性范围分别为1.295～25.890 μg·ml-1（r=0.999 9）、30.050～601.000 μg·ml-1（r=0.999 9）、1.874~37.480 μg·ml-1（r=0.999 9）,平均回收率分别为100.9%,100.3%,99.31%,RSD分别为0.92%,1.30%,0.89%。结论: 该法简便、快捷、结果准确、重复性好、实用性强,可以用于化瘀祛斑胶囊的质量控制。     

强力枇杷露质量标准的提高和优化

摘 要 目的：优化和提高强力枇杷露的质量标准。方法: 删去原质量标准中的化学反应,应用TLC法对处方中的罂粟壳、枇杷叶和桔梗进行鉴别;用HPLC法测定来源于罂粟壳的吗啡和磷酸可待因的含量。吗啡含量测定色谱条件为：色谱柱：Inertsil ODS 3（250 mm×4.6 mm,5 μm）,流动相：乙腈 0.01 mol·L-1庚烷磺酸钠溶液与0.02 mol·L-1磷酸二氢钾溶液的等量混合液（用10%磷酸溶液调节pH至2.8）（13∶〖KG-*2〗87）,检测波长：220 nm,柱温：30 ℃,流速：1.0 ml·min^-1;磷酸可待因含量测定色谱条件为：色谱柱：Inertsil ODS 3（250 mm×4.6 mm,5 μm）,流动相：乙腈 0.01 mol·L-1庚烷磺酸钠溶液与0.02 mol·L-1磷酸二氢钾溶液的等量混合液（用10%磷酸溶液调节pH至2.8）（15∶〖KG-*2〗85）,检测波长：220 nm,柱温：30 ℃,流速：1.0 ml·min^-1。结果:TLC法可用于鉴别罂粟壳、枇杷叶和桔梗;吗啡在3.14～62.80 μg·ml^-1的浓度范围内线性关系良好（r＝1.000 0）,平均回收率96.69%（RSD=2.41%,n=9）;磷酸可待因在3.52～87.94 μg·ml^-1范围内线性关系良好（r＝1.000 0）,平均回收率为95.68%（RSD=2.64%,n=9）。结论:改进了强力枇杷露的质量标准,建立的方法操作简易、精密度和准确度都好、专属性也强。     

HPLC法同时测定鼻炎愈合剂中阿魏酸、绿原酸和蒙花苷含量

摘 要 目的：建立HPLC法测定鼻炎愈合剂中阿魏酸、绿原酸和蒙花苷含量。方法: 以Agilent ZORBAX SB C18柱（250 mm×4.6 mm,5 μm）为色谱柱,流动相为乙腈 0.1%磷酸溶液,梯度洗脱,流速为1.0 ml·min-1,柱温30℃,检测波长326 nm。结果: 绿原酸、阿魏酸、蒙花苷分别在3.039 7~30.396 8 μg·ml-1 (r=0.999 7),3.999 9~39.999 4 μg·ml-1 (r=0.999 9),5.820 7~58.207 2 μg·ml-1(r=0.999 9)范围内与峰面积呈良好线性关系,其平均加样回收率分别为98.92%,100.81%,99.89%,RSD分别为1.00%,1.02%,0.99%（n=6）。结论: 该方法操作简便、准确、重现性好,可用于鼻炎愈合剂的质量控制。     

HPLC法同时测定根管消毒糊剂中3种成分的含量

摘 要 目的：建立高效液相色谱法（HPLC）同时测定根管消毒糊剂中多西环素、甲氧苄啶和醋酸地塞米松的含量。 方法: 色谱柱为Wonda Cract C18（250 mm×4.6 mm,5 μm）,流动相为甲醇 0.005 mol·L-1庚烷磺酸钠缓冲溶液（内含0.1%三乙胺）（梯度洗脱）,流速1.0 ml·min-1,检测波长240 nm,柱温25℃,进样量20 μl。 结果: 多西环素、甲氧苄啶和醋酸地塞米松的质量浓度分别在61 ~ 1 214 μg·ml-1（r=0.999 5）、57 ~ 1 137 μg·ml-1（r=0.999 7）和2~9 μg·ml-1（r=0.999 2）范围内与峰面积呈良好的线性关系;平均加样回收率及相应RSD分别为99.5%（RSD=1.21%）、100.4%（RSD=1.23%）和100.1%（RSD=1.20%）（n=9）。 结论: 该方法准确度好,精密度高,可用于多西环素、甲氧苄啶和醋酸地塞米松的同时测定。     

基于HPLC波长切换法对舒肝益脾液中7种成分的质量控制研究

摘 要 目的：建立HPLC波长切换法同时测定舒肝益脾液中7个成分。 方法: 色谱柱：Luna C18柱（250 mm×4.6 mm,5 μm）;流动相：乙腈 0.05％磷酸溶液,梯度洗脱;流速：0.9 ml·min-1;检测波长：345 nm（滨蒿内酯）、254 nm（毛蕊异黄酮苷、芒柄花苷、毛蕊异黄酮和芒柄花素）和210 nm（去氢茯苓酸和茯苓酸）;柱温：30 ℃,进样量：10 μl。结果: 滨蒿内酯、毛蕊异黄酮苷、芒柄花苷、毛蕊异黄酮、芒柄花素、去氢茯苓酸、茯苓酸7个成分的线性范围分别为6.09～152.25 μg·ml-1(r=0.999 9)、2.42～60.50 μg·ml-1(r=0.999 8)、1.61～40.25 μg·ml-1(r=0.999 6)、2.95～73.75 μg·ml-1(r=0.999 4)、6.88～172.00 μg·ml-1(r=0.999 9)、2.55～63.75 μg·ml-1(r=0.999 5)、2.09～52.25 μg·ml-1(r=0.999 9);平均加样回收率分别为98.96%（RSD=1.18%）,97.89%（RSD=1.41%）,97.18%（RSD=0.88%）,96.87%（RSD=0.97%）,99.32%（RSD=1.25%）,96.77%（RSD=0.86%）和98.55%（RSD=1.03%）（n=9）。结论: 本文建立的HPLC波长切换法同时测定舒肝益脾液中的7个成分,方法简便,可作为舒肝益脾液全面可靠的质量控制方法。     

加味小柴胡颗粒质量标准的建立

摘 要 目的：建立加味小柴胡颗粒的质量标准。方法: 采用TLC法对制剂中柴胡、黄芩、黄连进行定性鉴别;采用UPLC法对制剂中甘草苷、黄芩苷、盐酸小檗碱、汉黄芩苷、黄芩素、甘草酸单铵盐进行定量分析。色谱柱：Aglient ZORBAX Eclipse Plus C18（50 mm×2.1 mm,1.8 μm）,流动相：乙腈（A） 0.1%磷酸水（B）,流速：0.4 μml·min-1,检测波长： [0~11 min:270 nm;11~12 min:254 nm],柱温：35 ℃,进样量：2 μl。结果: 柴胡、黄芩、黄连的TLC图谱斑点清晰,分离度好;甘草苷、黄芩苷、盐酸小檗碱、汉黄芩苷、黄芩素、甘草酸单铵盐质量浓度分别在1.764~28.224 μg·ml-1（r=0.999 9）、12.390~198.240 μg·ml-1（r=0.999 7）、2.496~39.936 μg·ml-1（r=0.999 9）、4.200~67.200 μg·ml-1（r=0.999 5）、0.940~15.040 μg·ml-1（r=0.999 9）、1.872~29.950 μg·ml-1（r=0.999 6）浓度范围内线性关系良好;平均回收率分别为103.26%,101.36%,97.66%,103.27%,101.37%,102.44%,RSD分别为0.71%,0.81%,2.53%,1.58%,2.31%,3.34%（n=6）。结论: 所建质量标准能有效控制加味小柴胡颗粒的质量。     

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.