顶空气相色谱法同时测定硫酸阿扎那韦原料药中8种有机溶剂残留量

摘要：目的:建立同时测定硫酸阿扎那韦原料药中8种有机溶剂残留量的方法。方法:采用顶空气相色谱法,色谱柱为DM-624毛细管柱,程序升温:起始温度40℃,维持22 min,以100℃·min-1的速率升温至120℃,维持10 min;进样口温度为200℃,氢火焰离子化（FID）检测器;检测器温度为250℃;载气为高纯氮气,分流比为10∶1;柱流速为3.0 ml·min-1,顶空平衡温度为70℃,平衡时间为30 min,顶空进样体积为1 ml。结果:异丙醇、正庚烷、甲基叔丁基醚、四氢呋喃、二氯甲烷、甲醇、异丙醚和丙酮检测质量浓度线性范围分别为1.00～700.00μg·ml-1（r=0.997 9）、0.167～700.00μg·ml-1（r=0.996 7）、0.20～700.00μg·ml-1（r=0.998 3）、0.72～100.80μg·ml-1（r=0.999 0）、1.20～84.00μg·ml-1（r=0.998 8）、0.378～420.00μg·ml-1（r=0.998 2）、0.167～14.00μg·ml-1（r=0.998 2）、0.20～700.00μg·ml-1（r=0.998 7）;平均回收率分别为98.26%（RSD=2.67%）,100.1%（RSD=2.08%）,102.6%（RSD=1.88%）,100.1%（RSD=0.55%）,99.67%（RSD=1.08%）,98.58%（RSD=1.17%）,104.1%（RSD=1.93%）,100.7%（RSD=0.53%）（n=9）。结论:该方法操作简单、准确、专属性强、耐用性好,可用于硫酸阿扎那韦原料药中8种有机溶剂残留的同时测定。     

高效液相色谱法测定复方茶碱麻黄碱片的含量

建立高效液相色谱法测定复方茶碱麻黄碱片中可可碱、茶碱、盐酸麻黄碱及咖啡因的含量测定方法.采用Kromasil C18色谱柱;流动相0.05mol·L-1磷酸二氢钾溶液-甲醇-三乙胺(72280.2);检测波长215nm;流速1.0ml·min-1;柱温42℃.线性范围可可碱为5～125μg·ml-1(r=0.9999,n=6),茶碱为5～125μg·ml-1(r=0.9999,n=6),盐酸麻黄碱2～50μg·ml-1(r=0.9996,n=6),咖啡因3～75μg·ml-1(r=0.9999,n=6);平均回收率(X±SD)分别为可可碱(99.9±0.19)%,茶碱(99.9±0.26)%,盐酸麻黄碱(99.6±0.33)%,咖啡因(99.8±0.23)%.本方法简便、准确、重现性好,适用于复方茶碱麻黄碱片的质量控制.     

GC法测定盐酸达泊西汀原料药中有机溶剂的残留量

摘要：目的:建立GC法同时测定达泊西汀原料药中二甲胺、二氯甲烷、正己烷、乙酸乙酯、四氢呋喃、甲苯6种有机溶剂残留量的方法。方法:采用顶空气相色谱法。色谱柱为Agilent DB-624毛细管柱,程序升温,起始温度40℃,保持6 min,以20℃/min的速率升温至180℃,保持4 min,进样口温度为200℃,检测器温度为250℃,载气为氮气,流速1.5 ml·min-1,分流比为20∶1,进样方式为顶空进样,顶空平衡温度为80℃,平衡时间为20 min,进样量为5 ml。结果:6种待测有机残留溶剂的分离度均大于1.5,空白溶剂无干扰。二甲胺、二氯甲烷、正己烷、乙酸乙酯、四氢呋喃、甲苯检测质量浓度线性范围分别为1.00～50.17μg·ml-1（r=0.999 7）、1.21～60.25μg·ml-1（r=0.999 6）、1.01～29.63μg·ml-1（r=0.999 9）、10.00～500.19μg·ml-1（r=0.999 9）、1.45～72.46μg·ml-1（r=0.999 6）、1.79～89.50μg·ml-1（r=0.999 6）;定量限:0.20,0.15,0.35,0.50,0.30,0.25μg·ml-1;检测限:0.06,0.04,0.13,0.17,0.09,0.07μg·ml-1;加样回收率分别为98.01%～99.60%（RSD=0.54%）、98.14%～99.87%（RSD=0.64%）、98.80%～99.76%（RSD=0.37%）、98.02%～99.72%（RSD=0.50%）、98.04%～99.21%（RSD=0.45%）、98.10%～99.40%（RSD=0.39%）（n=9）。结论:该方法操作简单,重复性好,适用于达泊西汀原料药中6中有机溶剂残留的同时测定。     

气相色谱法同时测定醒脑静氯化钠注射液中冰片及麝香酮的含量

建立气相色谱同时测定醒脑静氯化钠注射液中冰片及麝香酮含量.以氯仿为溶剂提取醒脑静氯化钠注射液中的冰片及麝香酮,用聚乙二醇-20M毛细管色谱柱,FID检测器,程序升温140℃维持8分钟,再以30℃·min-1升温至200℃维持10分钟,采用外标法测定.结果冰片在13.65～271.8μg·ml-1浓度范围内线性相关(r=0.9999), 回收率为98.62%,RSD=1.80% ,(n=6);麝香酮在2～40μg·ml-1浓度范围内线性相关(r=0.9999),回收率为97.80%,RSD=1.37% ,(n=6). 该方法准确,灵敏,重现性好.     

顶空气相色谱法测定盐酸倍他司汀原料药中有机溶剂的残留量

目的:建立顶空气相色谱法测定盐酸倍他司汀原料药中乙醇、异丙醇、二氯甲烷3种有机溶剂残留量的方法。方法:色谱柱为DB-624石英毛细管柱,柱温70℃,检测器为氢火焰离子化检测器,检测器温度为250℃,进样口温度为180℃,以水为溶剂。结果:乙醇、异丙醇、二氯甲烷的检测浓度的线性范围分别为20～1000(r=1.0000)、20～1000(r=0.9999)、2.4～120(r=0.9998)μg·mL-1;平均回收率为98.6%～99.6%(RSD=0.1%～0.3%);检出限为0.49～1.89μg·mL-1;3批样品中3种有机溶剂残留量均符合《中国药典》要求。结论:本方法简单、准确、灵敏度高、重复性好,可用于该药物中有机溶剂残留量的测定。     

温郁金醋制前后5种成分含量变化考察

摘要：目的:比较温郁金醋制前后5种成分含量变化。方法:采用HPLC法对温郁金和醋温郁金中的莪术二酮、吉马酮、莪术醇、β-榄香烯、姜黄素5种成分进行定量分析。结果:莪术二酮、吉马酮、莪术醇、β-榄香烯、姜黄素5种成分能够良好分离,线性范围分别为2.506～20.050μg·ml-1（r=0.999 5）、0.919～7.355μg·ml-1（r=0.999 6）、0.964～7.714μg·ml-1（r=0.999 7）、0.927～7.416μg·ml-1（r=0.999 4）、1.123～8.982μg·ml-1（r=0.999 3）;平均加样回收率分别为99.59%（RSD=0.95%）,98.84%（RSD=0.91%）,99.41%（RSD=1.19%）,98.72%（RSD=0.79%）,98.94%（RSD=1.06%）（n=6）。温郁金经醋制后莪术二酮及吉马酮的含量显著降低（P<0.05）,莪术醇和β-榄香烯的含量则有所增加,而姜黄素含量无明显变化,5-羟甲基糠醛为炮制后新增加的成分。结论:基于HPLC法对温郁金和醋温郁金中5种成分进行定量分析,为进一步对温郁金炮制前后的质量变化和药效物质基础提供参考依据。     

顶空毛细管气相色谱法测定替卡西林钠原料药中的有机溶剂残留量

目的:建立测定替卡西林钠原料药中甲醇、乙醇、丙酮、二氯甲烷、乙酸乙酯、甲苯6种有机溶剂残留量的方法。方法:采用顶空气相色谱法。色谱柱为DB-624石英毛细管柱,柱温采用程序升温,检测器为氢火焰离子化检测器,检测器温度为250℃,进样口温度为150℃,以水为溶解介质。结果:甲醇、乙醇、丙酮、二氯甲烷、乙酸乙酯、甲苯的检测浓度的线性范围分别为12.0～1200(r=0.9999)、10.0～1000(r=0.9998)、10.0～1000(r=0.9999)、1.20～120(r=0.9997)、10.0～1000(r=0.9998)、1.78～178μg·mL-1(r=0.9996);平均回收率为98.5%～99.6%(RSD=0.6%～2.0%);定量限为0.20～11.80μg·mL-1;3批样品中6种有机溶剂残留量均符合《中国药典》要求。结论:本方法简单、准确、灵敏度高、重复性好,可用于该原料药中有机溶剂残留量的测定。     

气相色谱法测定吡非尼酮中残留溶剂含量

目的建立了吡非尼酮中6种有机溶剂残留量的分离测定方法。方法采用溶液直接进样气相色谱法,色谱柱为HP-INNOWAX毛细管柱(30 m×0.53 mm×2.65 m),载气为氮气,以N,N-二甲基甲酰胺为溶剂,测定了吡非尼酮原料药中异丙醚、丙酮、二氯甲烷、乙腈、二氧六环与吡啶的残留量。结果 6种有机溶剂完全分离,在所考察的浓度范围内线性关系良好,其中异丙醚、丙酮、二氯甲烷、乙腈、二氧六环与吡啶的线性范围分别为10.16~1 016μg.mL-1(r=0.999 99),9.92~992μg.mL-1(r=0.999 99),1.272~127.2μg.mL-1(r=0.999 8),0.848~84.8μg.mL-1(r=0.999 8),0.785~78.5μg.mL-1(r=0.999 9),0.416~41.6μg.mL-1(r=0.999 9)。各残留溶剂的精密度试验RSD均小于5%,平均回收率在96.22%~99.97%之间。结论本实验所建立的方法简便、灵敏、准确,可用于吡非尼酮中有机溶剂残留量的测定。     

UPLC法同时测定清心莲子饮中9个成分的含量

摘要：目的:建立超高效液相色谱法（UPLC）同时测定清心莲子饮中京尼平苷酸、毛蕊花糖苷、毛蕊异黄酮葡萄糖苷、黄芩苷、甘草苷、人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1和甘草酸铵9个成分含量。方法:采用UPLC方法,以AQUITY UPLC BEH C18（100 mm×2.1 mm, 1.8μm）为色谱柱,乙腈-0.1%磷酸溶液为流动相,梯度洗脱,流速0.2 ml·min-1,检测波长为205 nm和260nm,柱温30℃,进样量1.0μl。结果:京尼平苷酸、毛蕊花糖苷、毛蕊异黄酮葡萄糖苷、黄芩苷、甘草苷、人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1和甘草酸铵线性范围分别为26.14～470.50μg·ml-1（r=0.999 6）、30.33～545.90μg·ml-1（r=0.999 9）、16.48～296.60μg·ml-1（r=0.999 6）、87.80～1 580μg·ml-1（r=0.999 2）、12.33～221.90μg·ml-1（r=0.999 5）、5.85～105.30μg·ml-1（r=0.999 6）、7.75～139.60μg·ml-1（r=0.999 7）、9.03～162.50μg·ml-1（r=0.999 9）、32.88～591.8μg·ml-1（r=0.999 3）;平均加样回收率分别为98.48%,98.86%,98.73%,98.55%,97.97%,97.95%,98.55%,98.26%,98.86%（RSD＜2.0%,n=6）。结论:本文建立的含量测定方法操作简易,准确性和重复性好,可用于清心莲子饮的质量评价。     

梯度洗脱HPLC同时测定鼻腔洗剂Ⅱ号中3种有效成分含量

目的建立高效液相色谱法同时测定鼻腔洗剂Ⅱ号中甲硝唑、氯霉素和氢化可的松含量.方法采用高效液相色谱法.Intersil C18分析色谱柱(4.6mm×250mm,5μm),流动相为8%乙腈-乙腈梯度洗脱,流速1.6mL·min-1,检测波长245nm.结果甲硝唑、氯霉素和氢化可的松的理论板数分别为16000,12000,5000;回归方程分别为Y=-7.769+3.734×10-6×(r=0.9995),Y=13.97+4.111×10-6×(r=0.9999),Y=8.433+1.046×10-6×(r=0.9999);线性范围分别为52.00～416.0μg·ml-1,131.8～659.0μg·ml-1,21.40～107.0μg·ml-1;平均回收率(±RSD)分别为99.2%(±2.6%),100.4(±1.1%),100.3%(±0.85%);最低检出浓度分别约为0.6,0.6,0.3μg·ml-1.结论用高效液相色谱法同时测定鼻腔洗剂Ⅱ号中甲硝唑、氯霉素和氢化可的松含量,操作简便,结果准确.     

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.