毛细管气相色谱测定人血浆中5—单硝基异山梨醇酯

目的：建立测定人血浆中５－单硝基异山得醇酯（ＩＳ－５－ＭＮ）浓度的气相色谱检测法，方法：分析柱为ＨＰ－５毛细管柱，进样口，色谱柱及检测温度分别为２１０，１６０及２００℃，检测器为＾６３Ｎｉ电子捕获检测器，采用乙酸乙酯萃取血浆中ＩＳ－５－ＭＮ及内标２，４－二硝基甲苯。结果：ＩＳ－５－ＭＮ血药浓度在１０－８００ｎｇ／ｍｌ范围内线性关系良好（ｒ＝０．９９９８）最低检测浓度为５ｎｇ／ｍｌ，日内及日间差异均     

液相色谱—质谱联用技术及其在药物代谢研究中的应用

近２０多年来，液相色谱－质谱（ＬＣ－ＭＳ）联用技术已发展成为一种高度自动化、常规的应用分析手段，在各个领域得到了广泛应用。各种软离子化技术，特别是电喷雾（ＥＳＰ）离子喷雾（ＩＳＰ）大气压化学电离（ＡＰＣＩ）的引入，使ＬＣ－ＭＳ对高极性化合物的分析具独特优势，在药物代谢研究中发挥着日趋重要的作用，在很大程度上替代了传统的气相色谱－质谱（ＧＣ－ＭＳ）联用技术，简化了样品（特别是结合型代谢物）处理过程。     

气相色谱内标法测定蚕蛹油中α—亚麻酸含量

化学法提取的蚕蛹油经甲酯化后，采用气相色谱－质谱（ＧＣ／ＭＳ）技术，对蚕蛹油中脂肪酸的组分进行了分析，以十九烷酸（１９：０）甲酯作内标物，气相色谱法（ＧＣ）对蚕蛹油中α－亚麻酸进行了定量测定。结果表明蚕蛹油中α－亚麻酸的含量高达７２．８０％，本研究为α－亚麻酸的定量测定提供了实验依据。     

气相色谱——质谱法测定人血中丁螺环酮浓度

建立了血浆样品中盐酸丁螺环酮的气相色谱－质谱（ＧＣ－ＭＳ）联用的定量分析方法，血浆样品用二氯甲烷提取，采用ＧＣ－ＭＳ选择离子和辅助定量离子监测，方法的线性范围为０．５～５０ｎｇ／ｍｌ，回收率达８１％以上，并具有较好的准确度和精密度，该方法应用于盐酸相螺环酮临床药代动力学试验中血药浓度的测定，获得了准确，可靠的数据。     

人尿中安那度及其代谢物的分析研究

本文用ＧＣ／ＭＳ法研究安那度在人体内的代谢，检出了一个代谢产物。在下列色谱条件下对人尿中安那度母体药物及其代谢物进行了检测：ＨＰ５８９０Ａ－ＨＰ５９７０Ｂ气相色谱－质谱联用仪，ＨＰ－５２５ｍ×０．２ｍｍ石英毛细管柱，柱温：１００℃开始，以７℃／ｍｉｎ升温至２８０℃，保持５ｍｉｎ。方法回收率８１．４±２．６％（ｎ＝４），检测限２５ｐｇ。     

气相色谱—质谱法在滥用药物分析中的应用

滥用药物种类很多。，引起的后果也颇为严重气相色谱－质谱（ＧＣ－ＭＳ）法在滥用药物的分析检测中被广泛应用，本文综述了近年来对几种常见的滥用药物，包括阿片类、可卡因及其代谢物苯丙胺和甲基苯丙胺以及苯二氮类药物的ＧＣ－ＭＳ分析方法。     

垂体中蛋氨酸脑啡肽和β—内啡肽的定量分析

应用脱机液相色说和质谱联用定量分析了生物组织和体液中的内源神经肽,并用串联质谱（ＭＳ／ＭＳ）完善天然肽定量分析的分子专属性。反相高效液相色谱（ＲＰ－ＨＰＬＣ）用来纯化在生物组织和体液中的内源神经肽。液态二次离子质谱（ＬＳＩ－ＭＳ）,即快原子轰击质谱（ＦＡＢ）用来解吸和电离肽,定量分析时的内标选用相应的含有稳定同位素的合成肽。本文叙述了在人脑垂体中蛋氨酸脑啡肽（ＭＥ）和β－内啡肽（ＢＥ）的测定方法,     

人绝经促性腺激素分离纯化新方法

介绍了一种人绝经促性腺激素（ＨＭＧ）纯化新方法。该方法包括ＳＰ－Ｓｅｐｈａｄｅｘ色谱分离、Ｒ试剂处理、ＤＥＡＥ－Ｃ色谱分离、ＳｅｐｈａｄｅｘＧ－１００色谱分离。与现行方法比较，舍弃了乙醇溶液抽提、协和树脂吸附等较为繁琐的步骤。该法可将ＨＭＧ的促卵泡激素（ＦＳＨ）活性从０．９６ＩＵ／ｍｇ纯化提高至９６ＩＵ／ｍｇ。     

5—单硝酸异山梨酯缓释片相对生物利用度及药物动力学

目的：比较５－单耠酸异山梨酯（５－ＩＳＭＮ）缓释片产普通片的相对生物利用度和药物动力学，进行相对生物利用度及药物动力学参数测定。方法：１０名男性健康受试者交叉ｐｏ给药５－ＩＳＭＮ缓释片４０ｍｇ和普通片２０ｍｇ，以硝酸异山梨互为内标，用毛细管气相色谱－电子捕获（ＧＣ－ＥＣＤ）检测法测定人血浆中５－ＩＳＭＮ的浓度。结果：：两种剂型的药－时曲线均符合一室模型，单剂量时缓释片和普通片的ＡＵＣ０－∞分别为（     

高效液相色谱法测定人血浆中比索洛尔浓度

本文采用高效液相色谱（ＨＰＬＣ）内标法测定血浆中比索洛尔浓度。色谱柱为ＴＭＳ（７μｍ，０．４６ｃｍ×１５ｃｍ）；流动相为乙腈－磷酸二氢胺（１ｍｏｌ／Ｌ，ｐＨ４）－水（１８：５：７７），荧光检测波长２７５／３０５ｎｍ（Ｅｘ／Ｅｍ）。血浆样品经碱化二氯甲烷提取，催醒胺作内标。方法线性范围为２～５０ｎｇ／ｍｌ；检测下限２ｎｇ／ｍｌ；在５、１５和５０ｎｇ／ｍｌ３种浓度平均回收率为（８８．１±６．２）％；日内日间ＲＳＤ均小于８．０％。     

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.