高效毛细管电泳法测定人尿中氟罗沙星的含量

目的　建立高效毛细管电泳法测定人尿中氟罗沙星的含量。方法　采用高效毛细管电泳法 ,电泳缓冲液为磷酸盐 (5 0mmol·L-1) -SDS(10mmol·L-1) ,pH 4 .7,检测波长为 2 78nm。结果　在 5 0 .0～ 2 5 0 .0 μg·ml-1范围内线性良好 ,r =0 .9992。加样回收率在 94 .6 %～ 10 5 .9%之间 ,日内和日间RSD分别为 3.1%和 3.8% ,氟罗沙星的检测限为 2 .3μg·ml-1。结论　所用方法能快速、简便、经济地测定人尿中氟罗沙星的含量 ,可用于临床检验和药物制剂的质量控制     

HPLC法同时测定血浆地西泮及其代谢物浓度

目的 :建立同时测定血浆中地西泮及其代谢物浓度的方法。方法 :选用ZORBAXRP C18柱 (15 0mm× 4 6mm ,5 μm) ;甲醇 - 2 5mmol·L-1醋酸铵溶液 (6 0∶4 0 ,V/V)作流动相 ;流速 0 8mL·min-1;检测波长 2 30nm。取血浆样品 0 5mL ,在碱性条件下用二氯甲烷 -正己烷提取 ,HPLC检测。结果 :本法对替马西泮、去甲地西泮和地西泮 3种物质的最低检测限均为 2 μg·L-1,线性范围为 10～ 15 0 0 μg·L-1;奥沙西泮的最低检测限为 5 μg·L-1,线性范围为 2 0～ 15 0 0 μg·L-1。回收率均接近 10 0 % ,日内、日间RSD <5 %。结论 :本法能同时测定血浆中地西泮及其代谢物浓度 ,具有重现性好 ,灵敏、可靠 ,可用于地西泮中毒的监测     

氯霉素滴眼液及其相关物质二醇物的毛细管电泳分析法

目的　建立适合氯霉素滴眼液含量测定及其杂质二醇物检测的高效毛细管电泳定量检测方法。 方法 　采用毛细电泳法 ,以水杨酸为内标 ,运行电压 2 5 KV,运行缓冲液为 2 5 mmol· L- 1 磷酸盐缓冲液 (p H=6.0 ) ,检测波长 2 14 nm。结果 　氯霉素滴眼液及二醇物线性范围分别为 5 0～ 2 5 0 μg·ml- 1 (r=0 .9992 )和 4.0～ 2 0 .0 μg· ml- 1 (r=0 .9988)。平均回收率分别为 99.8%和 10 1.5 % ,RSD分别为 0 .8%和 2 .0 % (n=5 )。结论 　本方法能同时进行含量测定和杂质检测 ,对控制氯霉素滴眼液的质量有一定的价值     

高效液相色谱法测定异丁司特的血药浓度

目的 :建立高效液相色谱法测定人血浆中异丁司特浓度的方法。方法 :采用YWG C18色谱柱 ,以甲醇 0 .0 5mol·L-1磷酸二氢钾 (6 5∶35 ,用磷酸调pH值 3.5 )为流动相 ,检测波长 2 2 5nm ,流速 1.0mL·min-1,进样量 5 0 μL ,内标物为桂利嗪。 结果 :异丁司特标准曲线在 2～ 12 0 μg·L-1范围内线性关系良好 (r =0 .995 6 ) ,最低检测浓度为 2 μg·L-1,平均回收率为10 0 .2 % ,RSD为 4 .7% (n =5 )。结论 :该法操作简便 ,灵敏 ,准确度高 ,适用于异丁司特血药浓度的测定和药动学的研究。     

毛细管区带电泳法快速测定人血清中氯氮平含量

目的 :建立用毛细管区带电泳快速测定血清中氯氮平含量的方法。方法 :采用 33.5mmol·L-1磷酸盐缓冲液 (pH6 .47) ,用紫外检测器在 2 5 4nm波长处检测 ,以外标法定量。结果 :线性范围 0 .1～ 10 μg·ml-1,最低检测限 0 .1μg·ml-1。平均回收率 ( 97.47± 2 .8) %。日内与日间RSD分别为 2 .6 3%和 3.81%。结论 :毛细血管带电泳法是快速测定人血清中氯氮平含量的较好方法。     

HPLC-MS法测定人血浆中米氮平的浓度

目的 :建立一种用高效液相色谱 -电喷雾离子化质谱 (HPLC -MS)联用技术测定米氮平血药浓度的方法。方法 :以0 0 1mol·L-1乙酸铵水溶液∶甲醇 (2 7∶73,V/V)为流动相 ,盐酸地尔硫 艹卓 为内标 ,血浆样品经乙酸乙酯萃取后上样 ,经C18柱分离后 ,以质谱为检测器 ,采用选择性离子检测 (SIM)测定人体血浆中米氮平的浓度。结果 :米氮平的线性范围 0 2 0～ 15 0 μg·L-1(r=0 9995 ) ,平均相对回收率在 90 %～ 110 %之间 ,日内和日间RSD均 <5 % ,米氮平的最低定量限为 0 2 0 μg·L-1,提取回收率 >85 %。结论 :该方法快速、准确、灵敏 ,可用于米氮平的药动学研究     

高效液相色谱法测定人体液中5—氟胞嘧啶的浓度

目的 :用反相高效液相色谱法测定人体液中 5 -氟胞嘧啶的浓度 ,用于该药的治疗药物监测。方法 :样品处理用三氯乙酸沉淀蛋白后 ,于ODS色谱柱上分析 ,以 10mmol·L-1磷酸二氢钾 (用 0 1mol·L-1氢氧化钠溶液调pH至 7 0 )为流动相 ,流速 1 0mL·min-1,检测波长 2 80nm。结果 :线性范围为 6 2 5～ 2 0 0 μg·mL-1,最低检测限为 0 8μg·mL-1,平均方法回收率为 99 86 %。精密度考察 5 -氟胞嘧啶日内、日间RSD均小于 3%。结论 :本法快速简便 ,准确 ,重现性好 ,专一性强 ,适用于临床 5 -氟胞嘧啶治疗药物监测和药动学研究。     

高效液相色谱法测定人血浆中洛沙平的浓度

目的建立测定人血浆中洛沙平浓度的HPLC法.方法以DiamonsilTM C18反相柱(250 mm×4.6 mm,5 μm)为色谱柱,流动相为甲醇-0.03 mol·L-1醋酸铵(8713),流速为0.8 mL·min-1,检测波长257 nm,以乙醚为提取剂.结果洛沙平的高(585.6 μg·L-1)、中(292.8μg·L-1)、低(36.6 μg·L-1)3个浓度的平均回收率分别为95.29%,96.77%,97.89%,日内(n=5)、日间(n=3)RSD均小于6%;分析方法的最低定量限为6.1 μg·L-1.线性范围为6.1～732.0μg·L-1,回归方程为C=562.72F-30.33,r=0.999 3(n=9).结论该方法灵敏、准确、简单、快速,可用于临床血药浓度监测和药动学研究.     

高效液相色谱法同时测定血浆中艾司唑仑、三唑仑和阿普唑仑浓度

目的 :建立同时测定血浆中艾司唑仑、三唑仑和阿普唑仑浓度的方法。方法 :采用HPLC法 ,选用ZORBAXRP C18柱(15 0mm× 4 .6mm ,5 μm) ;甲醇 2 5mmol·L-1醋酸铵溶液 (5 7∶4 3)作流动相 ;检测波长为 2 30nm。结果 :本法对三唑仑、阿普唑仑和艾司唑仑的最低检测限浓度均为 4 μg·L-1;回收率接近 10 0 % ;日内、日间精密度 <5 % ;线性范围均为 2 0～ 10 0 0 μg·L-1。结论 :本法能同时测定血浆中三唑仑、阿普唑仑和艾司唑仑 ,此法重现性好 ,灵敏 ,可靠 ,可用于临床药物中毒监测。     

利伐沙班原料药中重金属镍残留量的

目的：建立利伐沙班原料药中金属催化剂镍残留的两种测定方法,并对不同方法进行比较分析。方法：方法一采用石墨炉原子吸收分光光度法;方法二采用电感耦合等离子体质谱法。结果：方法一在10～100 μg·L-1范围内线性良好,最低检出浓度为1.9 μg·L-1,方法检测限为0.2 μg·g-1,加标回收率平均为112%;方法二在0.5～20 μg·L-1范围内线性良好,最低检出浓度为0.056 μg·L-1,方法检测限为0.007 μg·g-1,加标回收率平均为97.9%。结论：6批样品的检验结果表明,两种方法对结果的测量无明显差异,但电感耦合等离子体质谱法具有分析速度快、检测限更低、灵敏度高以及可多种元素同时测定等优点,在重金属痕量分析检测方面更具优势。     

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.