高效液相色谱法手性拆分奥美拉唑对映异构体

目的：手性拆分奥美拉唑对映异构体,建立检查埃索美拉唑钠原料药中R-异构体的HPLC方法。方法：采用Chiral pak IC手性柱（4.6 mm×250 mm,5 μm）,以正己烷-异丙醇-甲醇-三乙胺（40∶40∶20∶0.1,v/v/v/v）为流动相,检测波长为302 nm,柱温为30 ℃,流速为1.0 mL·min^-1。结果：埃索美拉唑及其R-异构体的分离度（R）大于7。R-异构体的检测限和定量限分别为32 ng·mL^-1和80 ng·mL^-1,线性范围为0.5~30 μg·mL^-1。自制三批埃索美拉唑钠盐中R-异构体的含量均为0.02%,R-异构体的限度符合要求。结论：该方法简便,快速,可用来检查埃索美拉唑钠原料药中R-异构体的限度。     

GC法同时测定香砂养胃片中去氢木香内酯、厚朴酚、和厚朴酚的含量

目的：建立气相色谱（GC）法测定香砂养胃片中去氢木香内酯、厚朴酚与和厚朴酚的含量。方法：采用色谱柱为WondaCAP5 30 m×320 μm×0.25 μm毛细管色谱柱;检测器：FID检测器。进样口温度：250 ℃;柱温箱温度：210 ℃;检测器温度：280 ℃;载气流速：3.0 mL·min-1;进样量：1 μL。结果：去氢木香内酯在1.996~199.6μg·mL-1;厚朴酚在5.123~512.3 μg·mL-1;和厚朴酚在2.609~260.9μg·mL-1的范围内,线性关系良好（r＞0.999 1）平均回收率分别为97.3%（RSD=1.1%）、98.6%（RSD=1.2%）和97.4%（RSD=1.9%）结论： 建立方法简单、准确、重现性好,可用于控制香砂养胃片中3种活性成分的含量。     

HPLC法测定硼替佐米原料药中的异构体

摘 要 目的：建立同时测定硼替佐米原料药中3种光学异构体含量的方法。 方法: 采用HPLC法,色谱柱：ChiralPAKAY-H正相手性柱（250 mm×4.6 mm,5 μm）;流动相：正己烷 乙醇 甲醇 三氟乙酸（90∶7.5∶2.5∶0.1）;流速：0.8 ml·min^-1;检测波长：270 nm;柱温：40℃;进样量：5 μl。结果: 硼替佐米与3种光学异构体之间的分离度均大于2.0;3种光学异构体的线性范围均为0.6～20 μg·mL^-1（r≥0.999 7）;平均回收率分别为104.1%,105.5%,92.0%,RSD分别为2.3%,2.4%,2.7%（n=9）;定量限和检测限均分别为3 ng和1 ng。结论:该方法快速、准确度高,可用于测定硼替佐米中的光学异构体。     

HPLC法同时测定金胆片中龙胆苦苷等4种主成分的含量

建立高效液相色谱法同时测定金胆片中4种主要活性成分含量的方法。方法：采用Agilent Eclipse X DB C18（4.6 mm×250 mm,5 μm)色谱柱;以乙腈(A) -0.1%磷酸溶液(B)为流动相梯度洗脱,检测波长为270 nm;柱温为30 ℃;流速1.0 mL·min-1。结果：龙胆苦苷、虎杖苷、槲皮素和大黄素质量浓度分别在7.875~78.75 μg·mL-1（r=0.999 9）、6.75~67.50 μg·mL-1（r=0.999 7）、7.726~77.26 μg·mL-1（r=0.999 4）、3.809~38.09 μg·mL-1（r=0.999 8）范围内与峰面积呈良好的线性关系,平均加样回收率分别为99.31%、99.21%、99.04%、99.59% (n=6),RSD分别为1.86%、1.24%、1.37%、1.15%。结论： 该实验方法准确性可靠、重复性和稳定性良好,专属性强,可为金胆片的质量控制和标准提升提供参考依据。     

反相离子对色谱法测定复方双氯芬酸钠注射液的含量

目的建立反相离子对色谱法（RPIC）同时测定复方双氯芬酸钠注射液中盐酸利多卡因和双氯芬酸钠的含量。方法色谱柱：Alltech C18（150 mm×4.6 mm，5 μm）；流动相：0.05 mol·L 1磷酸二氢钠缓冲液（用磷酸调pH值2.8） 乙睛（40∶60）配制的4 mmol·L 1的庚烷磺酸钠溶液；流速1.0 mL·min 1；检测波长：213 nm；柱温：室温。结果盐酸利多卡因在20～120 μg·mL 1范围内线性关系良好（r＝0.999 9），平均回收率99.9 %，重复性实验RSD ＝0.3%(n＝6)；双氯芬酸钠在75～450 μg·mL 1范围内线性关系良好，平均回收率99.5%，重复性实验RSD为 0.5%(n＝6)。结论该法简便准确，可用于复方双氯芬酸钠注射液的含量测定。     

HPLC测定盐酸烟酰美金刚胺中的烟酸及其他有关物质

目的 采用HPLC法测定盐酸烟酰美金刚胺中的烟酸及其他有关物质.方法 采用Luna SILICA色谱柱(150 mm×4.6 mm,5μm),以正庚烷-乙醇-冰乙酸(90∶ 10∶1)为流动相,检测波长260 nm.结果 烟酰美金刚胺与烟酸及其他降解产物的分离度良好;0.50～10.0 μg·mL-1盐酸烟酰美金刚胺、0.25～5.0 μg·mL-1烟酸与峰面积的线性关系良好,r分别为0.9997、0.9999;烟酸的检测限和定量限分别为0.12、0.39 μg·mL-1,加样回收率为99.7％.结论 所用方法专属性好、结果准确,可用于盐酸烟酰美金刚胺中烟酸及其他有关物质的测定.     

RP-HPLC法测定药用胶塞中16种多环芳烃含量 并作模拟提取研究

目的：本试验通过高效液相色谱法测定药用胶塞中16 种多环芳烃（PAHs）的含量并作迁移试验。方法：色谱柱为Kromasil 100-5-C18 (4.6 mm × 250 mm,5 μm);以乙腈和水为流动相,采用梯度洗脱进行分离：0~27 min,乙腈-水（65∶35）;27~41 min,乙腈-水（65∶35）→（100∶0）;41~43 min,乙腈-水（100∶0）→（65∶35）;43~55 min,乙腈-水（65∶35）。检测波长：220、254、295 nm。结果：16种PAHs在0.1000~10.00 μg·mL-1浓度范围内线性关系良好,均r≥0.999;定量限在2.505~83.20 ng·mL-1;检测限在0.751 5~24.96 ng·mL-1;精密度RSD均≤2.0%;重复性RSD≤3.0%;平均加样回收率为88.74%~99.27%。试验同时考察16 种多环芳烃（PAHs）的迁移试验,以验证该方法。结论：试验采用的RP-HPLC法测定16种PAHs方法专属性良好,能够快捷、简便、准确、灵敏地测定药用胶塞中16种PAHs的含量,可适用于橡胶胶塞中 PAHs的测定以及考察注射液中16种PAHs的迁移。     

RP-HPLC法测定药用胶塞中16种多环芳烃含量 并作模拟提取研究

目的：本试验通过高效液相色谱法测定药用胶塞中16 种多环芳烃（PAHs）的含量并作迁移试验。方法：色谱柱为Kromasil 100-5-C18 (4.6 mm × 250 mm,5 μm);以乙腈和水为流动相,采用梯度洗脱进行分离：0~27 min,乙腈-水（65∶35）;27~41 min,乙腈-水（65∶35）→（100∶0）;41~43 min,乙腈-水（100∶0）→（65∶35）;43~55 min,乙腈-水（65∶35）。检测波长：220、254、295 nm。结果：16种PAHs在0.1000~10.00 μg·mL-1浓度范围内线性关系良好,均r≥0.999;定量限在2.505~83.20 ng·mL-1;检测限在0.751 5~24.96 ng·mL-1;精密度RSD均≤2.0%;重复性RSD≤3.0%;平均加样回收率为88.74%~99.27%。试验同时考察16 种多环芳烃（PAHs）的迁移试验,以验证该方法。结论：试验采用的RP-HPLC法测定16种PAHs方法专属性良好,能够快捷、简便、准确、灵敏地测定药用胶塞中16种PAHs的含量,可适用于橡胶胶塞中 PAHs的测定以及考察注射液中16种PAHs的迁移。     

HPLC双波长法同时测定桑白皮水提物中6个成分的含量

目的：建立HPLC双波长法同时测定桑白皮水提物中桑皮苷A、绿原酸、单宁酸、桑根酮D、桑酮G、桑根酮C等6个主要成分的含量。方法：色谱柱为Phenomenex Gemini C18 （250 mm × 4.6 mm，5 μm）；以乙腈为流动相A，0.2%甲酸水溶液为流动相B，梯度洗脱；检测波长：270 nm（单宁酸、桑根酮D、桑酮G、桑根酮C）、320 nm(桑皮苷A、绿原酸)；柱温：30℃；流速：1.0 mL·min-1；进样量：20 μL。结果：桑皮苷A、绿原酸、单宁酸、桑根酮D、桑酮G、桑根酮C分别在3.24 ～ 647.20 μg·mL-1、3.22 ～ 643.60 μg·mL-1、2.50 ～ 588.80 μg·mL-1、3.28 ～ 656.80 μg·mL-1、3.19 ～ 637.20 μg·mL-1、3.10 ～ 619.60 μg·mL-1质量浓度范围内与峰面积线性关系良好（r ＞ 0.999）；加样平均回收率分别为99.18%、99.06%、98.96%、98.76%、98.99%、98.90%（n = 9），其RSD分别为0.45%、0.33%、0.59%、0.36%、0.47%、0.49%。结论：该方法的准确度、重复性、耐用性均良好，适合用于桑白皮水提物中桑皮苷A等6个主要成分的定量测定。     

超高效液相色谱法测定富马酸伏诺拉生原料有关物质

目的：建立超高效液相色谱法测定富马酸伏诺拉生有关物质的方法。方法：采用ZORBAX SB-C18色谱柱(4.6 mm×150 mm,1.8 μm),流动相A为0.025 mol·L-1磷酸盐缓冲溶液(pH 6.0)- 甲醇-乙腈(14∶5∶1),流动相B为0.025 mol·L-1磷酸盐缓冲溶液(pH 6.0)-乙腈(3∶7), 采用梯度洗脱,流速1.0 mL·min-1,柱温30 ℃,检测波长230 nm,进样量20 μL。结果：杂质A、 杂质C、杂质D、杂质F、杂质G、杂质H、杂质J、杂质K、杂质L、杂质M、杂质N和伏诺拉生分别在0.04177~2.088 μg·mL-1(r=1.0000)、0.07479~3.740 μg·mL-1(r=1.0000)、0.07335~3.668 μg·mL-1(r=1.0000)、0.1000~2.004 μg·mL-1(r=1.0000)、0.1325~6.623 μg·mL-1(r=1.0000)、 0.09300~1.860 μg·mL-1(r=1.0000)、0.1380~2.7530 μg·mL-1(r=1.0000)、0.1350~2.698 μg·mL-1 (r=1.0000)、0.1130~2.257 μg·mL-1(r=1.0000)、0.05060~2.530 μg·mL-1(r=0.9999)、 0.1420~2.846 μg·mL-1(r=1.0000)、0.1190~2.382 μg·mL-1(r=0.9998)浓度范围内与峰面积呈良好线性关系。上述各杂质的平均回收率(n=9)分别为97.24%、102.12%、99.46%、98.29%、101.51%、 100.84%、99.18%、101.20%、98.49%、103.63%、96.49%。采用该检测方法对5批样品进行有关物质检测,其中杂质C、杂质M、杂质N检出量均≤0.05%,杂质H、其他最大单个杂质检出量均≤0.10%,总杂质检出量均≤0.31%。结论：经方法学验证,本法专属性强、灵敏度高、准确度高,可用于富马酸伏诺拉生原料的有关物质测定,为其质量控制提供方法保证。     

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.