氢溴酸高乌甲素中有机溶剂残留量HL-GC 检测方法的建立

目的：建立测定氢溴酸高乌甲素中4种有机溶剂残留量的顶空毛细管气相色谱方法。方法采用DB-624毛细管柱（30 m ×0.53 mm,3μm）,程序升温,起始柱温40℃,维持7 min,以25℃·min-1的速率升至200℃,维持1 min;进样口温度：200℃;FID 检测器,检测器温度：250℃;进样方式：顶空进样,平衡温度：80℃,平衡时间：30 min;载气为N2;以DMF为溶剂对氢溴酸高乌甲素中乙醇、乙酸乙酯、三氯甲烷和苯的残留量进行测定。结果4种有机溶剂分离度良好,乙醇、乙酸乙酯、三氯甲烷和苯浓度分别在129.2-1033μg·mL-1（r=0.999）、120.5-964.2μg·mL-1（r=0.999）、3.32-26.5μg·mL-1（r=0.998）、0.14-1.13μg·mL-1（r=0.997）范围内线性关系良好;平均回收率（n=9）分别为97.4%、97.4%、96.8%、98.1%,RSD 分别为1.3%、2.0%、1.7%、3.1%。结论本文建立的顶空毛细管气相色谱法,经方法学验证可用于氢溴酸高乌甲素中有机溶剂残留量的测定,可作为该药质量标准修订的参考。     

GC测定褪黑素类似物中有机溶剂残留量

目的 建立毛细管气相色谱法测定褪黑素类似物AGO中乙醇、乙酸乙酯、二氯甲烷、四氢呋喃、甲苯5种有机溶剂的残留量。方法 采用DB-Wax(30 m×0.45 mm,0.85 μm)毛细管色谱柱;氢火焰离子化检测器(FID);程序升温：初始温度45 ℃(维持9 min),以30 ℃.min-1速率升温至200 ℃(维持9 min);载气为氮气,柱流速为3.5 mL.min-1;进样口温度：200 ℃;检测器温度：250 ℃;分流直接进样,二甲基亚砜为溶剂,乙腈为内标物,内标法测定残留溶剂的含量。结果 各组分分离完全,在所考察的浓度范围内线性关系良好,其中乙醇、乙酸乙酯、二氯甲烷、四氢呋喃、甲苯的线性范围分别为107.44 μg.mL-1~1074.4 μg.mL-1(r=0.9999),108.24 μg.mL-1~1082.4 μg.mL-1(r=0.9997),18.550 μg.mL-1~185.50 μg.mL-1(r=0.9998),14.208 μg.mL-1~142.08 μg.mL-1(r=0.9994),19.074 μg.mL-1~190.74 μg.mL-1(r=0.9999),平均回收率为98%~102%。结论 该方法操作简单,精密度好,准确可靠,可用于该药物有机溶剂残留量的测定。     

GC法同时测定聚山梨酯80中5种挥发性杂质

目的建立气相色谱法对聚山梨酯80中的环氧乙烷、二氧六环、氯乙醇、乙二醇和二甘醇5种挥发性杂质进行同时检测。方法采用气相色谱法,色谱柱固定相为PEG20000(GsBP-INOWAX,30m×0.53mm×1.0μm弹性石英毛细管柱)。采用程序升温,初温50℃,以5℃·min-1升温至200℃,保持10min,再以50℃·min-1升温至230℃,保持20min。进样口温度为200℃,检测器温度为250℃。结果同时测定了聚山梨酯80中环氧乙烷、二氧六环、氯乙醇、乙二醇和二甘醇5种挥发性杂质,线性范围分别为2.7~176.8μg·mL-1(r=0.999 8),2.8~140.7μg·mL-1(r=0.999 8),3.4~167.5μg·mL-1(r=0.999 9),4.7~2 345μg·mL-1(r=0.999 8)和3.2~160.8μg·mL-1(r=0.999 9);平均加样回收率分别为104.3%,91.3%,105.2%,94.1%和105.7%,RSD分别为2.5%,2.8%,1.4%,3.0%和3.7%。结论该方法灵敏、准确,可用于聚山梨酯80中挥发性杂质的检测。     

毛细管气相色谱法测定舒必利中有机溶剂残留量

目的：建立气相色谱法测定舒必利中3种有机溶剂的残留量的方法.方法：采用HP-1毛细管色谱柱（30.0 m×0.53 mm,5μm）;进样口温度为205℃;FID检测器温度为280℃;柱温：程序升温,60℃保持5 min,然后以20℃·min-1的速率升温120℃,保持5 min;以氮气为载气,载气流速为3.0 ml· min-1;直接进样,进样量为1μl;以N,N-二甲基甲酰胺为溶剂.结果：甲醇,乙醇和乙二醇及溶剂峰彼此均能良好分离,线性范围分别为1.51 ～ 301.72 μg·ml-1（r =0.999 9）,1.51 ～ 502.56μg·ml-1（r =0.999 9）,4.11～65.76 μg·ml-1（r =0.999 1）;平均回收率分别为93.6％,91.7％,92.8％,RSD分别为2.5％,3.0％,5.7％（n=9）.结论：该法准确可靠,适用于舒必利中这3种有机溶剂残留量的测定.     

去羧氯雷他定中有机溶剂残留量检查的研究

目的：测定去羧氯雷他定原料药中残留有机溶剂乙醇和乙酸乙酯的含量.方法：采用气相色谱法,顶空进样,FID检测器,以1,4-二氧六环为溶剂,异丙醇为内标,采用石英毛细管柱,以6%苯基-94%氰基丙基苯基二甲基聚硅氧烷为固定相,气化室150o C,检测器240o C,柱温65o C.结果：乙醇在10～220 μg/ml浓度范围内呈良好的线性关系（r＝0.999 9）,回收率为99.03%（RSD=2.5%）,最低检出限为1 μg/ml. 乙酸乙酯在10～200 μg/ml浓度范围内呈良好的线性关系（r＝0.999 9）,回收率为101.5%（RSD=1.2%）,最低检出限为3 μg/ml.三批去羧氯雷他定原料药中乙醇的残留量均为0.02%,乙酸乙酯的残留量均为0.03%.结论：本方法简单、快捷且灵敏度高,可用于去羧氯雷他定中乙醇和乙酸乙酯残留量的控制.     

气相色谱法测定人血白蛋白中乙醇残留量

目的：建立气相色谱法测定人血白蛋白中乙醇残留量。方法：采用DB-624毛细管色谱柱（30 m×0.32 mm×1.8 μm）;氢火焰离子化检测器（FID）;进样口温度为200 ℃,检测器温度为250 ℃;载气为氮气,载气流速为2.0 mL·min-1;采用程序升温法：起始温度为40 ℃,保持8 min,以50 ℃·min-1速度升温至200 ℃,保持5 min。进样方式为顶空进样,顶空平衡温度为80 ℃,平衡时间为30 min。结果：乙醇在1.005 6 ~ 377.097 5 μg·mL-1范围内与峰面积线性关系良好（r为0.999 8,n=9）;精密度的RSD为2.5%,重复性的RSD为1.5%;平均加样回收率为100.2%（n=9,RSD为3.4%）。定量限为1.005 6 μg·mL-1,检出限为0.335 2 μg·mL-1。测定人血白蛋白原液59 批和成品78 批,均低于250 μg·mL-1。结论：该方法操作简单、结果准确,灵敏度高,专属性强,可用于人血白蛋白中乙醇残留量测定。     

顶空气相色谱法测定布美他尼原料药中残留的溶剂

目的建立测定布美他尼原料药中两种有机溶剂甲苯和乙醇残留量的顶空气相色谱法。方法采用DB-1型石英毛细管柱（30 m×0.53 mm,1.5μm）,载气为氮气,FID检测器;程序升温,起始温度35℃维持3 min,再以55℃/min升温至90℃,维持1.5 min。结果两种有机溶剂完全分离,乙醇与甲苯质量浓度分别在3.7～33.3μg/mL（r=0.999 8）及3.6～32.4μg/mL（r=0.999 6）范围内与相应的峰面积之比呈良好的线性关系;平均回收率分别为100.37%和97.01%,RSD分别为0.80%和1.12%（n=9）;乙醇、甲苯的最低检测限分别为0.02μg/g和0.05μg/g（S/N=3）。结论该方法灵敏、准确、重现性好,可用于实际生产中的质量控制。     

气相色谱法同时测定尼尔雌醇原料药中7种有机溶剂的残留量

目的:建立同时测定尼尔雌醇原料药中甲醇、乙醇、乙腈、异丙醇、甲苯、四氢呋喃和乙酸乙酯残留量的方法。方法:采用气相色谱法。色谱柱为DB-WAX毛细管柱,检测器为氢火焰离子化检测器,分流比为5∶1,载气为氮气(纯度:99.999%),流速为1.0 mL/min,进样量为1μL,直接进样,固定相为键合交联聚乙二醇,升温程序为初始温度40℃,保持5 min,以10℃/min速率升温至90℃,再以5℃/min速率升温至200℃,进样口温度为220℃,检测器温度为230℃。结果:甲醇、乙醇、乙腈、异丙醇、甲苯、四氢呋喃和乙酸乙酯的检测质量浓度线性范围分别为0.24～12.00μg/mL(r=0.999 7)、0.40～20.00μg/mL(r=0.999 5)、0.033～1.64μg/mL(r=0.999 8)、0.40～20.00μg/mL(r=0.999 5)、0.071～3.56μg/mL(r=0.999 6)、0.058～2.88μg/mL(r=0.999 8)、0.40～20.00μg/mL(r=0.999 7);定量限分别为0.24、0.40、0.033、0.40、0.071、0.058、0.40μg/mL,检测限分别为0.08、0.10、0.01、0.13、0.02、0.02、0.13μg/mL;精密度、稳定性、重复性试验的RSD均小于2%;加样回收率分别为98.17%～100.48%(RSD=0.92%,n=9)、97.77%～101.30%(RSD=1.32%,n=9)、97.56%～100.85%(RSD=1.20%,n=9)、98.64%～100.92%(RSD=0.87%,n=9)、98.54%～100.62%(RSD=0.76%,n=9)、98.26%～100.00%(RSD=0.74%,n=9)、98.30%～100.59%(RSD=0.76%,n=9)。结论:该方法灵敏度较高、准确度较好,可用于同时测定尼尔雌醇原料药中甲醇、乙醇、乙腈、异丙烷、甲苯、四氢呋喃和乙酸乙酯的残留量。     

GC法同时测定冰珍去翳滴眼液中冰片和苯氧乙醇的含量

目的：建立气相色谱法同时测定冰珍去翳滴眼液中冰片及苯氧乙醇的含量。方法： 采用DB-WAX毛细管色谱柱（30 m × 0.32 mm,0.25 μm）;FID检测器;进样口温度200 ℃,检测器温度为250 ℃;载气为氮气,流速为1 mL·min-1。采用程序升温法：起始温度130 ℃,保持10 min,以25 ℃·min-1升至200 ℃,保持5 min。结果：天然冰片、苯氧乙醇的质量浓度分别在0.011 54～0.115 4 mg·mL-1（r=0.999 9）、0.064 87～0.648 7 mg·mL-1（r=0.999 9）范围内线性关系良好;平均回收率分别为96.3%（RSD=1.65%）、95.1%（RSD=1.62%）。结论：该方法专属性好,准确度高,重复性好,可用于冰珍去翳滴眼液的质量控制。     

毛细管气相色谱法测定瑞舒伐他汀钙中有机溶剂残留量

目的:建立毛细管气相色谱法测定瑞舒伐他汀钙中有机溶剂的残留量.方法:采用HP-FFAP毛细管色谱柱,载气为氮气,流速为6 ml·min-1;分流比为5:1;程序升温;氢火焰离子化检测器(FID),检测器温度250℃,进样口温度200℃;按外标法测定溶剂残留量.结果:乙醇、乙酸乙酯、四氢呋喃和甲苯分别在100.58～1 005.80(r=0.999 9)、102.00～1 020.00(r=0.999 9)、14.66～146.60(r=0.999 9)、19.12～191.20 μg·m1-1(r=0.999 9)范围内,线性关系良好;平均回收率分别为99.1%(RSD=2.0%),98.5%(RSD=1.6%),98.9%(RSD=1.8%),99.2%(RSD=2.1%).结论:该方法专属性好、快速、简单、结果准确,可用于瑞舒伐他汀钙中有机溶剂残留量的测定.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.