HPLC法测定乙胺吡嗪利福异烟片中4组分含量

目的：建立高效液相色谱法，测定乙胺吡嗪利福异烟片中利福平、异烟肼、吡嗪酰胺和盐酸乙胺丁醇含量。方法：利福平、异烟肼和吡嗪酰胺用C18色谱柱（150mm×4．6mm，5μm），以-0．01M磷酸二氢钾溶液-乙腈为流动相进行梯度洗脱，流速1．0ml·min^-1，检测波长254nm。盐酸乙胺丁醇选用C18色谱柱（150mm×4．6mm，5μm），四氢呋喃-0．4％庚烷磺酸钠（含有0．016％硫酸铜，用磷酸调pH至4．5）（25：75）为流动相，流速1．0ml·min^-1，检测波长258nm。结果：利福平、异烟肼、吡嗪酰胺及盐酸乙胺丁醇线性范围分别为16～160μg·ml^-1（r=0．9999），16—160μg·ml^-1（r=0．9999），53—532μg·ml^-1（r=0．9998），80～320μg·ml^-1（r=0．9998），平均回收率为99．3％～99．5％。结论：方法简便，准确，可用于乙胺吡嗪利福异烟片中各组分的质量控制。     

高效液相色谱法测定吡嗪酰胺片的含量

目的：建立高效液相色谱法测定吡嗪酰胺片中吡嗪酰胺的含量。方法：以十八烷基硅烷键合硅胶为固定相，水－甲醇（90：10）为流动相，检测波长为268nm，外标法定量。结果：线性范围10．0－50．0μg.ml^-1（r＝0．9997），平均回收率99．7％，RSD为0．7％（n=6)。结论：本法简便快捷，结果准确，适用于该产品的含量测定检验。     

RP—HPLC同时测定利福肼胺胶囊中三组分的含量

用RP－HPLC法测定利福肼胺胶囊中利福平、异烟肼和吡嗪酰胺含量。采用Delta pak C18色谱柱,流动相分别为甲醇－pH4．5磷酸盐缓冲液（75：25）和甲醇-pH 3．5磷酸盐缓冲液（6：94）,检测波长254nm。方法回收率为99．5％－100．2％,RSD均小于1．60％。     

国家食品药品监督管理局国家药品标准（修订）颁布件：异福酰胺胶囊

本品为含利福平、异烟肼和吡嗪酰胺的复方制剂，含利福平（C43H58N4O12）、异烟肼（C6H7N3O）、吡嗪酰胺（C5H5N3O）均应为标示量的90．0％～110．0％。     

HPLC法测定结核病患者血浆中异烟肼、吡嗪酰胺和利福平的质量浓度

目的：建立快速、灵敏的同时测定人血浆中异烟肼、吡嗪酰胺和利福平的质量浓度的高效液相色谱法。方法血浆样品采用甲醇沉淀蛋白法萃取,采用C18色谱柱（150mm×4．6mm,5．0μm）,用甲醇、乙腈、0.05mol·L-1KH2PO3水溶液（三乙胺调pH6.0）进行梯度洗脱,柱温40℃,进样量20μL,采用PDA紫外检测器。结果以峰面积外标法定量,异烟肼在0．20～25．6μg·mL-1范围内,与峰面积线性关系良好（r＝0．9998）,吡嗪酰胺在0．20～25．6μg·mL-1范围内,与峰面积线性关系良好（r＝0．9999）,利福平胶囊在0．40～25．6μg·mL-1范围内,与峰面积线性关系良好（r＝0．9996）,回收率为85％～115％,日内、日间精密度RSD均＜9．4％（n＝5）。结论该方法专属性强、灵敏、准确,适用于同时测定人血浆样品中异烟肼、吡嗪酰胺和利福平的质量浓度。     

反相高效液相色谱法测定格拉司琼片中主药的含量

目的：建立格拉司琼片中主药格拉琼的含量测量方法。方法：采用反相高效液相色谱法,在Spherisorb,C18色谱柱上,以乙腈－0．02mol.L^-1 磷酸二氢钾缓冲液（含3％三乙胺,pH2.2）＝25：75作流动相,流速1ml.min^-1, 检测波长301nm,进样量20ul考察了流动相pH,流动相中三乙胺用量等因素对色谱分离的影响,结果：格拉司琼与片剂科和有关杂质可完全分离,格拉司琼线性范围10．5－63．0ug.ml^-1 ,平均回收率为100．0％,RSD＜1．7％,结论：该法操作方便,专属性强,结果准确,重现性好。     

高效液相色谱法测定血清中富马酸奎的平浓度

目的：建立用高效液相色谱法（HPLC）测定血清中富马酸奎的平浓度的方法。方法：HPLC测定，流动相为甲醇－水－1mol.L^-1醋酸铵－5mol.L^-1氨水（400：100：5：1）的混合液体,pH9.7，流速1mL.min^-1，C18柱，紫外检测波长254nm，以外标法定量。结果：线性范围10－300ug.L^-1，最低检测限5ug.L^-1，平均提取回收率93．10％，日内与日间精密度平均分别为3．41％和4．16％,结论：用HPLC可以较好的对血清中富马酸奎的平进行定性和定量。     

毛细管气相色谱法测定复方利福平片中异烟肼和吡嗪酰胺的含量

目的：建立复方利福平片中异烟肼和吡嗪酰胺的含量测定方法。方法：毛细管气相色谱法,以乙酰苯胺为内标,色谱柱为弹性石英毛细管柱２５ｍ ×０ ．３２ｍ ｍ ×０ ．５２μｍ （ＤＢ１） ;柱温１７０ ℃;气化室温度２５０ ℃;检测器温度２５０ ℃;载气为高纯氮。结果：异烟肼和吡嗪酰胺的线性范围分别是０ ．４２６ ～２ ．１３ｍｇｍｌ 和１ ．２３ ～６ ．１３ｍｇｍｌ;平均回收率分别为９９ ．８１ ％ 和９９ ．６３ ％ 。结论：方法简便,快速,准确,可作为该制剂的检测方法。     

HPLC法测定异福胶囊中异烟肼和利福平的含量

目的：建立异福胶囊中同时测定异烟肼和利福平的含量的方法。方法采用HPLC梯度洗脱法,色谱柱为十八烷基硅烷键合硅胶为填充柱（Agilent ZORBAX Eclipse XDB－C18,4．6mm ×250mm,5μm）,流动相分别为流动相A：甲醇－0．015mol? L －1磷酸二氢钠溶液（用磷酸调节pH值为6．5）（5∶95）,流动相B：甲醇－0．015mol? L－1磷酸二氢钠溶液（用磷酸调节pH值为6．5）（62∶38）;流速：1．3mL? min －1,检测波长：262nm。结果以峰面积（y）对进样浓度（x）线性回归,异烟肼回归方程：y＝29773x－7020．2,r＝0．9998,线性范围为11．48～183．6μg? mL －1;利福平回归方程：y＝35061x－67601,r＝0．9997,线性范围为13．78～275．6μg? mL －1,峰面积与浓度呈良好的线性关系。异烟肼和利福平加样回收率分别为：分别为100．1％和99．9％（n＝9）,RSD分别为O．23％和0．26％。结论本方法操作简便、准确、重现性好,可用于同时测定异福胶囊中异烟肼和利福平的含量。     

高效液相色谱法测定人血浆中异烟肼和吡嗪酰胺的浓度

目的:建立以高效液相色谱法测定人血浆中异烟肼及吡嗪酰胺浓度的方法.方法:色谱柱为Diamonsil C18( 250 mm ×4.6 mm,5μm),以0.05 mol ·L-1磷酸二氢钾溶液∶甲醇=89∶11(用三乙胺调节pH约为6.0)为流动相,柱温:室温,流速:0.9ml·min-1,检测波长为254 nm.结果:异烟肼的线性范围为0.5～30μg·ml-1(r =0.998 5),吡嗪酰胺线性范围为1～50μg ·ml -1(r =0.998 0),平均回收率分别为90.33％,103.01％.结论:本法专属性好,样品处理方法简单,可用于测定人血浆中异烟肼和吡嗪酰胺的浓度.     

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.