Cherkaoui S, Rudaz S, Veuthey J L
Laboratory of Pharmaceutical Analytical Chemistry, University of Geneva, Switzerland.
Electrophoresis. 2001 Feb;22(3):491-6. doi: 10.1002/1522-2683(200102)22:3<491::AID-ELPS491>3.0.CO;2-4.
Aqueous and nonaqueous capillary electrophoresis (NACE) were investigated for separation of venlafaxine, a new second-generation antidepressant, and its three phase I metabolites. Working at basic pH, around the venlafaxine pKa value, was effective in resolving the investigated drugs, but created considerable peak tailing. To overcome electrostatic interactions between analytes and silanol groups, investigations were also carried out at acidic pH. However, despite the addition of up to 50% v/v of organic solvents (e.g., methanol or acetonitrile), complete separation of the studied compounds was not possible. NACE was found to be an appropriate alternative to resolve venlafaxine and its metabolites simultaneously. Using a conventional capillary (fused-silica, 64.5 cm length, 50 microm inner diameter), and a methanol-acetonitrile mixture (20/80 v/v) containing 25 mM ammonium formate and 1 M formic acid, complete resolution of these closely related compounds was performed in less than 3.5 min. Selectivity, efficiency and separation time were greatly affected by the organic solvent composition. As the electric current generated in nonaqueous medium was very low, the electric field was further increased by reducing the capillary length. This allowed a baseline resolution of venlafaxine and its three metabolities in 0.7 min. Selectivity was compared in aqueous and nonaqueous media in relation to the acid-base properties of the analytes as well as to the solvation degree. Finally, the method successfully coupled on-line to mass spectrometry with electrospray ionization interface allowed significant sensitivity enhancement.
研究了水性和非水性毛细管电泳（NACE）用于分离新型第二代抗抑郁药文拉法辛及其三种I相代谢物。在接近文拉法辛pKa值的碱性pH条件下进行分离，对所研究的药物有较好的分离效果，但会产生相当严重的峰拖尾现象。为克服分析物与硅醇基团之间的静电相互作用，还在酸性pH条件下进行了研究。然而，尽管加入了高达50%（v/v）的有机溶剂（如甲醇或乙腈），仍无法实现所研究化合物的完全分离。结果发现NACE是同时分离文拉法辛及其代谢物的合适替代方法。使用常规毛细管（熔融石英，长度64.5 cm，内径50μm），以及含有25 mM甲酸铵和1 M甲酸的甲醇 - 乙腈混合物（20/80，v/v），在不到3.5分钟内实现了这些密切相关化合物的完全分离。有机溶剂组成对选择性、效率和分离时间有很大影响。由于非水介质中产生的电流非常低，通过缩短毛细管长度进一步增加了电场强度。这使得文拉法辛及其三种代谢物在0.7分钟内实现了基线分离。根据分析物的酸碱性质以及溶剂化程度，对水性和非水介质中的选择性进行了比较。最后，该方法成功地与带有电喷雾电离接口的质谱仪在线联用，显著提高了灵敏度。
