HPLC法同时测定依托泊苷植入剂的有关物质及含量

目的建立一种常规高效液相色谱法测定依托泊苷植入剂的有关物质及含量。方法采用C18柱,乙腈一醋酸盐缓冲液（pH4．0）（2：5）（取醋酸钠5．44g,加水溶解并稀释至2000ml,用冰醋酸调节pH值至4．0）为流动相,检测波长：230nm。降解产物制备方法为将溶液置80℃水浴中破坏30min。结果该法能很好地分离依托泊苷及有关物质,检测限为0．05μg。结论本方法同时检测依托泊苷植入剂的有关物质及含量,方法准确、方便、实用性强。     

反相离子对色谱法分离加替沙星有关物质及其片剂含量测定

目的建立加替沙星有关物质的分离检测及其片剂的含量测定方法.方法采用反相离子对色谱(RPIC)法,色谱柱为ODS柱,流动相为0 .02mol*L-1磷酸二氢钾缓冲液(用磷酸调pH 4.5)-乙腈(82∶18)配制的0.003mo l*L-1四丁基溴化铵溶液,流速为1.0mL*min-1;检测波长为293nm,柱温为4 0℃.结果建立的色谱方法使有关物质与主药分离良好,加替沙星在4～40μg*mL-1范围内,浓度与峰面积线性关系良好,平均回收率100.2%,RSD=1.8%.结论本法简便、准确,可用于加替沙星有关物质的检查及片剂含量测定.     

缓释制剂的体内外相关性试验及检验

目的：探讨缓释制剂体内外相关试验方法。方法：以植入用缓释依托泊苷为例，根据体内及体外预试验数据，求算对应时间点关联系数K，按中华人民共和国药典要求作对应时间点的点对点相关试验及检验。结果：成功进行植入用缓释依托泊苷的体内外相关试验并实现相关。结论：此法为长效缓释制剂提供了一种体内外相关试验的参考方法。     

反相离子对高效液相色谱法测定唑来膦酸粉针剂中的主药和有关物质

目的:建立唑来膦酸粉针剂中有关物质和主药含量的测定方法.方法:采用反相离子对高效液相色谱法,色谱柱为BDS柱(200mm×4.6mm,5μm),流动相为0.08%磷酸溶液-0.1%四丁基氢氧化胺溶液(100∶15,用三乙胺调pH值为4.02),流速1.0mL*min-1,检测波长217nm,柱温为室温.结果:本法使有关物质与主药分离良好,唑来膦酸在40.50～141.8μg*mL-1范围内,峰面积与浓度线性关系良好,平均回收率99.64%(n=9),RSD为0.87%.结论:本法操作方便,结果准确,重现性好,可用于唑来膦酸粉针剂中有关物质的检查及主药的含量测定.     

反相高效液相色谱法测定塞克硝唑的含量及其有关物质

目的采用反相高效液相色谱法测定塞克硝唑的含量及其有关物质.方法采用Inertsil ODS C18色谱柱(5μm,4.6 mm×150 mm),以乙腈-水(10∶90)为流动相,流速1.5 mL*min-1,检测波长320nm.结果反相高效液相色谱法测定的线性范围为0.5～700.0μg*mL-1,相关系数r=0.9999;日内精密度为0.38%(n=6),日间精密度为0.44%(n=6).结论采用反相高效液相色谱法测定塞克硝唑的含量及有关物质,方法简便、快速、准确、专属性好.     

阿司匹林单硝酸异山梨酯复方缓释片含量测定方法的研究

目的建立阿司匹林单硝酸异山梨酯复方缓释片中阿司匹林和单硝酸异山梨酯含量及有关物质检测的高效液相色谱法。方法采用Thermo ODS-2 Hypersil(4.6 mm×200 mm,5μm)色谱柱,以0.02 mol.L-1的磷酸二氢钾溶液-甲醇-磷酸(70∶30∶0.1)为流动相,流速1.0 mL.min-1,柱温为40℃,检测波长为225 nm。结果阿司匹林和单硝酸异山梨酯分别为浓度在15.06～120.48μg.mL-1和12.09～96.72μg.mL-1范围内线性关系良好,平均回收率分别为99.55%和99.12%,RSD分别为0.58%和0.54%。结论建立的高效液相色谱法可以同时测定复方缓释片中阿司匹林和单硝酸异山梨酯的含量和有关物质,该方法准确度和精密度高,适合应用于该制剂的质量控制。     

氯酚伪麻缓释片中氯雷他定的HPLC分析研究

目的:建立氯酚伪麻缓释片中氯雷他定的高效液相色谱(HPLC)测定方法.方法:使用Hypersil C18柱(150mm×6.0mm,5μm);流动相为0.01mol·L-1磷酸氢二钾(用10%磷酸调节pH至6.80)-甲醇(20:80);检测波长为247nm.结果:氯雷他定与片剂中其他原料、辅料及有关物质分离良好,方法回收率为100.2%,RSD为0.4%(n=9).结论:本法简便、专属,可用于氯酚伪麻缓释片中氯雷他定的含量测定.     

植入用缓释依托泊苷(VP-16)的药代模型—血浓方程初探

探讨并建立了植入用缓释依托泊苷的药代模型。结果显示 ,经 13例试验者数据拟合 ,其药代模型为 :单室 ,单剂量植入给药 ,血浓方程 C=A1 e- Ke t+ A2 e- Ka t+ A3e- Kr t。     

离子对色谱法测定复方西吡氯铵含片中维生素C及有关物质

目的:采用反相离子对高效液相色谱法测定复方西吡氯铵含片中维生素C及有关物质.方法:采用Shimadzu CLC-ODS柱(150mm×6.0mm,5μm),以甲醇-水(含0.005mol*L-1十六烷基三甲基溴化铵和0.050mol*L-1磷酸二氢钾)(10∶90)为流动相,流速为1.0mL*min-1,检测波长为254nm.结果:离子对高效液相色谱法测定的线性范围为5.0～200μg*mL-1,相关系数r=0.999 9;日内精密度为0.52%(n=6),日间精密度为0.86%(n=6);平均回收率为99.54%(n=9).结论:采用反相离子对高效液相色谱法测定复方西吡氯铵含片中维生素C的含量及其有关物质,方法简便、快速、准确、专属性好.     

RP-HPLC测定盐酸卡替洛尔骨架缓释微丸的含量及有关物质

目的建立盐酸卡替洛尔骨架缓释微丸的含量及有关物质测定方法。方法采用VP-ODSC18柱(4.6mm×150mm,4.6μm),以0.067%的Na2HPO4溶液(用H3PO4调节pH至3.0)-乙腈(87∶13)为流动相,流速为1mL/min,检测波长为251nm,柱温30℃。结果盐酸卡替洛尔与有关物质及破坏后的降解成分能够完全分离;盐酸卡替洛尔浓度在2~40μg/mL范围内与峰面积线性关系良好,r=0.9997;平均加样回收率为101.2%,RSD=0.36(n=9);最低检出限为0.4ng,最小定量限为1.6ng。结论该方法操作简便、准确、快速、灵敏度高,可用于盐酸卡替洛尔骨架缓释丸的含量及有关物质测定。     

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.