衍生化分光光度法快速测定卡托普利片中主药的含量

目的:建立以衍生化分光光度法快速测定卡托普利片中主药含量的方法。方法:在氢氧化钠碱性条件下,采用2,4-二硝基氟苯作为衍生化试剂,与卡托普利在水浴40℃暗处反应后,以342nm为检测波长,通过紫外-可见分光光度法测定卡托普利的含量。结果:卡托普利检测浓度线性范围为1.0～14.0μg·mL-1(r=0.9999),平均回收率为99.61%,RSD=1.27%(n=9),日内、日间RSD均小于2%。结论:该方法稳定、可靠,操作简便、快速,可用于卡托普利片中主药的含量测定。     

衍生化HPLC柱切换法测定人血浆中卡托普利浓度的方法研究

目的 :建立高效液相色谱柱前衍生化结合柱切换技术测定血浆中卡托普利浓度的方法。方法 :血浆中卡托普利与对溴苯甲酰甲基溴发生衍生化反应后 ,分别加入等体积的丙酮和水 ,离心后取上清液进样 ,以HPLC柱切换进行分离测定。结果 :线性范围为 2 0～ 10 0 0ng·mL-1,净化回收率为 94 7%～ 96 2 % ,方法回收率为 98 1%～ 10 3 8% ,日内和日间检测RSD分别小于 2 8%和 4 2 %。结论 :方法简便灵敏 ,为卡托普利人体药代动力学研究及临床药物监测提供了方法     

高效液相色谱法测定人血浆中卡托普利和人体药动学的研究

目的　建立简便的测定人血浆中卡托普利血药浓度的高效液相色谱法 ,研究卡托普利在健康人体中的药动学参数。方法　以对溴苯乙酰基溴为紫外衍生化试剂 ,采用高效液相色谱紫外检测法测定 18名健康志愿受试者口服单剂量卡托普利受试制剂和参比制剂 ( 5 0mg)后血药浓度。结果　卡托普利的血药浓度标准曲线的线性范围为 2 5～ 12 0 0ng·mL- 1 ,其最低定量限为 2 5ng·mL- 1 ,日内及日间RSD均小于 8%。应用所建立的血药浓度检测方法测定 18名健康志愿受试者口服单剂量卡托普利受试制剂和参比制剂 ( 5 0mg)后血药浓度 ,并计算药动学参数。结果表明口服受试制剂或参比制剂后的tmax分别为( 0 6 4± 0 18)h和 ( 0 82± 0 4 1)h ;Cmax分别为 ( 6 0 0 2± 194 3)ng·mL- 1 和 ( 5 82 7± 175 3)ng·mL- 1 ;AUC0→ 8h分别为 ( 14 4 8 5± 4 83 7)ng·h·mL- 1 和 ( 1389 9± 392 5 )ng·h·mL- 1 ;AUC0→∞ 分别为 ( 186 9 4± 70 1 6 )ng·h·mL- 1 和 ( 1781 8± 6 15 5 )ng·h·mL- 1 。结论　本方法操作便捷 ,灵敏度高 ,为血药浓度监测及药代动力学研究提供了方法学基础     

溴莫普林颗粒剂的药代动力学与生物利用度研究

目的 :研究溴莫普林颗粒剂在正常人体药代动力学与生物利用度。方法 :采用高效液相色谱法 ,以非那西丁作内标 ,测定溴莫普林血浆药物浓度 ,用于 18名健康志愿受试者随机交叉口服溴莫普林颗粒剂和片剂各 4 0 0 m g后的血药浓度测定。结果 :两种制剂在健康人体内药物动力学均符合口服开放性二室模型 ,颗粒剂与片剂比较相对生物利用度为 (10 0 .2±4 .9) %。结论 :经统计分析两种制剂具有生物等效性     

优化的液相色谱-串联质谱联用法测定人血浆中卡托普利的浓度及其药动学研究

目的：建立人血浆中卡托普利浓度的液相色谱-串联质谱联用（LC-MS/MS）法优化测定方法。方法：取待测人血浆0.5 ml,加入维生素C和乙二胺四乙酸（EDTA）溶液防止氧化,加入对溴苯甲酰甲基溴溶液衍生化后,经酸化,乙酸乙酯提取、浓缩,取上清液20μl进样分析。流动相为甲醇-水（70∶30）（10 mmol/L醋酸铵,醋酸调pH值3.5）,色谱柱为江苏汉邦C18柱（150 mm×4.6 mm,5μm）,流速为1.0 ml/min,LC-MS/MS多反应离子检测,正离子模式,用于定量分析的离子分别是卡托普利m/z 414.1→216.2和地西泮m/z 285.4→193.2。结果：卡托普利的线性范围为1～100 ng/ml,方法的回收率〉80%,批内和批间的精密度均〈15%,稳定性符合生物样品测定要求。结论：本方法特异性强、快速、灵敏度高,相比以前报道的方法更适用于血药浓度的测定和药代动力学研究。     

衍生化分光光度法测定控释制剂中卡托普利含量相关条件的考察

目的:考察渗透泵型控释制剂中卡托普利最佳的衍生化测定条件。方法:以2,2’-二硫二吡啶(2-PDS)为衍生化试剂,通过研究卡托普利与2-PDS的反应时间、反应体系的pH的变化以及pH调节方法对卡托普利最终测定结果的影响。结果:卡托普利在pH6.8的溶液中衍生化60min,能够达到稳定的最大紫外吸收。结论:该方法操作简单,能够准确稳定测定出渗透泵型控释制剂中卡托普利的含量,且重复性好,适用于本品制剂的含量检测。     

人体卡托普利的药代动力学及其生物利用度

目的：比较Ａ、Ｂ两厂复方卡托普利片的生物利用度和药代动力学。方法：９名健康志愿者随机交叉口服单剂量３０ｍｇ复方卡托普利片,以对溴苯乙酰基溴（ＰＢＰＢ）为衍生化试剂,采用反相高效液相色谱法。结果：测得Ａ、Ｂ药厂生产的复方卡托普利片剂在血浆中Ｃａｐ浓度达峰时间分别为（０．９４±０．１３）ｈ和（１．００±０．１５）ｈ;达峰浓度Ｃｍａｘ分别为（９２．０３±２７．３６）ｎｇ／ｍｌ、（７４．６７±１９．２９）ｎｇ／ｍｌ;药时曲线下面积（ＡＵＣ）分别为（２５２．７８±６８．１４）ｎｇ／（ｈ·Ｌ）、（２５１．１９±５０．１３）ｎｇ／（ｈ·Ｌ）。血药浓度—时间曲线符合二房室模型。结论：以Ａ厂复方卡托普利片为标准算得Ｂ厂复方卡托普利片中卡托普利的相对生物利用度（Ｆ）为９９．３７％。     

固相萃取结合柱前衍生化RP-HPLC法测定人血浆中的卡托普利的浓度及其药动学与相对生物利用度研究

本文建立固相萃取结合柱前衍生化测定人血浆中的卡托普利浓度的RP-HPLC法,并利用该方法研究两种国产卡托普利片在健康受试者中的药物动力学与相对生物利用度。以对溴苯乙酰基溴 (p-BPB) 为衍生化试剂,衍生化产物经固相萃取后由VP-ODS 柱分离测定,流动相为乙腈-水-冰醋酸 (100:150:1.25) (v/v),紫外检测波长为257 nm,线性范围为 5~1000 ngmL-1,(r=0.9987),平均回收率为 98.652.04%,日内和日间 RSD 分别小于3.4% 和 8.4%。以自身对照随机交叉方式,单计量分别给予18名健康男性志愿者两种国产卡托普利片50 mg,卡托普利在人体内符合一室开放模型。两种卡托普利片的AUC0-T,Cmax 和 Tmax 分别为424.5125.7 mghL-1 和439.4113.3 mghL-1,505.9244.6 mgL-1和 504.8172.2 mgL-1,0.6620.181 h和0.5280.176 h。两种制剂间的各参数无明显差异,双单侧t检验结果表明二者为生物等效制剂,其相对生物利用度为96.114.6%。     

溴莫普林颗粒剂的药代动力学与生物利用度研究

目的:研究溴莫普林颗粒剂在正常人体药代动力学与生物利用度。方法:采用高效液相色谱法,以非那西丁作内标,测定溴莫普林血浆药物浓度,用于18名健康志愿受试者随机交叉口服溴莫普林颗粒剂和片剂各400mg后的血药浓度测定。结果:两种制剂在健康人体内药物动力学均符合口服开放性二室模型,颗粒剂与片剂比较相对生物利用度为(100.2±4.9)%。结论:经统计分析两种制剂具有生物等效性。     

盐酸莫西沙星片剂的血药浓度及药动学分析

目的 分析盐酸莫西沙星在人体内的血药浓度及药动学.方法 10名志愿受试者单剂量口服莫西沙星400mg后,采用固相萃取-高效液相色谱方法测定盐酸莫西沙星的血药浓度及药动学参数,用DAS2.0软件自动拟合处理,计算药动学参数.结果 莫西沙星的药动参数:t1/2α=(5.26±0.20)h;t1/2 β=(7.80±0.50)h;AUC(0～t)=(111.8±10.3)μg/ (mL·h);tmax=(3.13±0.32)h;Cmax=(13.5±0.42) μg/ mL;莫两沙星在体内的药-时曲线符合二室开放模型,在体内消除半衰期为12h,生物利用度约为95.4％.结论 该方法操作简单、准确可靠,可用于莫西沙星的临床药动学研究及临床特殊人群的血药浓度测定.     

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.