手性流动相添加剂法拆分比索洛尔对映体

以羧甲基-β-环糊精作为手性流动相添加剂,建立了高效液相色谱拆分比索洛尔对映体的方法。系统考察了手性添加剂的种类及浓度、流动相中甲醇的含量、pH值和流速等因素对拆分的影响。色谱分离条件:流动相甲醇∶乙腈∶水为20∶67∶13(V/V/V),羧甲基-β-环糊精浓度为0.5g.L-1,pH值为4.07(以三乙胺-冰乙酸调节),流速为0.3mL.min-1,检测波长223nm,对映体得到基线分离,分离度为1.89。     

直链淀粉手性固定相高效液相色谱法拆分比索洛尔对映体

采用直链淀粉手性固定相高效液相色谱法在正相条件下直接拆分了比索洛尔对映异构体。分别以异丙醇、乙醇为有机改性剂,考察了流动相的组成与配比、流速及柱温等因素对比索洛尔对映体分离的影响。确定了比索洛尔对映体的最佳拆分条件:流动相正己烷-乙醇-二乙胺(体积比为88∶12∶0.1),流速0.6 mL/min,检测波长270 nm,柱温20 ℃。该方法可快捷、简便地拆分比索洛尔对映体。     

Liquid chromatography tandem mass spectrometry method for determination of bisoprolol in human plasma using d5‐bisoprolol as the internal standard

A simple, reliable and sensitive liquid chromatography tandem mass spectrometry (LC‐MS/MS) protocol was developed and validated for quantification of bisoprolol in human plasma. The sample was pretreated with a simple procedure of protein precipitation and an isotope‐labeled d5‐bisoprolol was used as internal standard. The chromatographic separation was performed on a Capcell Pak C₁₈ MG III column (100 mm × 2.0 mm, 5 µm). The protonated ion of the analyte was detected in positive ionization by multiple reaction monitoring mode. The mass transition pairs of m/z 326.3 → 116.3 and m/z 331.3 → 121.3 were used to detect bisoprolol and the internal standard, respectively. Linearity, accuracy, precision, recovery, matrix effect, dilution test and stability were evaluated during method validation over the range of 0.5–100 ng/mL. The validated method was successfully applied to analyze human plasma samples in a bisoprolol bioavailability study. Copyright © 2009 John Wiley & Sons, Ltd.     

参松养心胶囊与比索洛尔治疗心律失常疗效对比观察

为进一步探讨参松养心胶囊的临床安全性,对其在治疗心律失常上的疗效与比索洛尔(康忻)的疗效进行了比较.将100例心律失常患者随机分为2组:治疗组为50例,参松养心胶囊口服,每次4粒,每日3次;对照组50例,比索洛尔口服,每次5mg,每日1次.疗程定为3个月,观察结果是:治疗组与对照组在治疗心律失常上临床疗效无统计学差异(P>0.05);而在不良反应方面有统计学差异(P<0.05).可见参松养心胶囊在治疗心律失常上与比索洛尔相比具有安全有效的优势.     

比索洛尔的结构表征及其透皮性能研究

利用元素分析、IR、1H-NMR和13C-NMR等方法对比索洛尔的结构进行了表征,并研究了促渗剂对比索洛尔贴剂体外透皮性能的影响。以离体豚鼠皮肤为透皮屏障,采用改进的Franz扩散池,通过体外渗透性实验对含不同促渗剂的几组比索洛尔贴剂进行了透皮性能的研究。结果表明：体外渗透曲线符合零级方程（Q = k·t）,含3% 月桂氮酮（Azone）和10% 肉豆蔻酸异丙酯（IPM）的复合促渗剂的比索洛尔贴剂具有良好的透皮性能。将加入复合促渗剂的贴剂中比索洛尔的透皮速率与不加促渗剂贴剂的透皮速率比较,贴剂中药物的透皮性能有明显提高。     

手性毛细管电色谱拆分比索洛尔、阿替洛尔、克仑特罗和特布他林

以万古霉素(vancomycin)毛细管柱为手性分离色谱柱,采用CLC和pCEC方法,对比索洛尔、阿替洛尔、克仑特罗和特布他林进行了手性拆分研究。在CLC方法中,上述4种物质均在甲醇/异丙醇/三乙胺/冰醋酸(60/40/0.05/0.1,V/V)条件下获得最大分离,分离度(Rs)分别为1.9、1.4、1.1和0.9。在pCEC方法中,采用极性有机模式时,Rs分别为1.9、1.4、1.5和1.5;采用反相模式时,Rs分别为2.0、1.7和1.2,而特布他林则未获分离。该方法能有效拆分比索洛尔、阿替洛尔、克仑特罗和特布他林,而且CLC、pCEC极性有机模式和pCEC反相模式之间有着较强的互补关系。     

A Novel Molecularly Imprinted Potentiometric Sensor for the Fast Determination of Bisoprolol Fumarate in Biological Samples

In this study, molecularly imprinted polymer (MIP) was prepared and used in the preparation of carbon paste electrode (CPE) for the quantification of bisoprolol fumarate (BF) in pure, pharmaceutical formulation and biological fluids. The selective MIP for BF was synthesized from methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the cross-linker in dimethyl sulfoxide solution, BF as the template molecule and 2, 2-azobisisobutyronitrile (AIBN) as the initiator. The non-imprinted polymer (NIP) was synthesized by the same procedure, but in the absence of the template molecule then incorporated in the paste of the carbon paste electrodes (CPEs). The prepared MIP for BF and its corresponding NIP were well characterized using scanning electron microscopy (SEM), Fourier transform infrared spectrometer, and thermal gravimetric analysis (TGA). The MIP and NIP based CPEs were further used for the determination of BF and the obtained results indicated that the sensor modified by the MIP have much higher recognition power for the BF molecules than the NIP based sensor where the MIP based CPE exhibited a Nernstian response 29.50±0.55 mV decade⁻¹ within a concentration range of 1.0×10⁻⁷–1.0×10⁻² mol L⁻¹and pH independence in the range 3.50–7.15. The proposed sensor has high selectivity over several possible interfering compounds. The obtained results by the proposed sensor were satisfactory with excellent percentage recovery and relative standard deviation and were comparable with those obtained from HPLC reported method.     

富马酸比索洛尔合成中的杂质分析及控制

在富马酸比索洛尔的制备中, 发现了1 种从未被报道的、含量较高的杂质,通过1H-NMR、13C-NMR、MS和HPLC对其进行了溯源分析和结构确证,并定向合成了该杂质,根据其产生根源,优化醚化反应工艺条件。结果表明,当n(对异丙氧基乙氧基甲基苯酚) : n(环氧氯丙烷)= 1 : 1.2,以蒸馏水为溶剂,NaOH为催化剂,反应温度70 ℃,反应时间4 h时,该杂质的含量得到了有效控制,并通过精制使最终产品富马酸比索洛尔中的该杂质去除掉,其它杂质含量不超过0.1%。     

慢性心力衰竭联用螺内酯和比索洛尔的临床效应

目的：观察慢性心力衰竭联用螺内酯和比索洛尔的临床效应。方法：选择96例慢性心力衰竭患者，随机分为对照组48例和观察组48例，对照组采用常规治疗，观察组在常规治疗基础上加用螺内酯联合比索洛尔。在治疗前和观察期满12周时。分别进行测定心率、血压、血清钾离子浓度、肾功能及心脏超声检测左室收缩末期内径（LVEDs），左室舒张末期内径（LVEDd）和左室射血分数（LVEF）。结果：治疗12周后，总有效率95．8％、心率明显下降、心脏LVEDs及LVEDd缩小，LVEF提高均有统计学意义（P〈0．05）。结论：螺内酯联合比索洛尔治疗慢性心力衰竭疗效确切，无明显不良反应。     

手性药物富马酸比索洛尔的合成研究

富马酸比索洛尔为选择性β1-肾上腺素能受体阻滞剂,介绍了一种不对称合成S-富马酸比索洛尔和R-富马酸比索洛尔的新方法。以R-环氧氯丙烷和S-环氧氯丙烷为手性原料,直接与4-((2-异丙氧基乙氧基)甲基)-苯酚缩合,再经开环得到化合物S-比索洛尔和R-比索洛尔,最后与富马酸成盐制得S-富马酸比索洛尔和R-富马酸比索洛尔。