高效毛细管电泳联用电喷雾-质谱法研究新型抗癌铂配合物的稳定性  

Application of High Performance Capillary Electrophoresis Tandem Mass Spectrometry to the Investigation on the Stability of Novel Anticancer Platinum Complex in Solution

作　　者：苏强[1] 刘清飞[2] 吴娟芳[3] 王义明[3] 毕开顺[1] 刘伟平[4] 罗国安[2] 

机构地区：[1]沈阳药科大学药学院,沈阳110016 [2]清华大学医学院,北京100084 [3]清华大学化学系,北京100084 [4]昆明贵金属研究所,昆明650221

出　　处：《分析化学》2007年第12期1721-1725,共5页Chinese Journal of Analytical Chemistry

摘　　要：研究了新型抗癌铂配合物3，5-二异丙基水杨酸-1，2-环己二胺合铂（11）（SM54111）在溶液中的稳定性。采用高效毛细管电泳（HPCE）法，分离在pH3．7～9．0的缓冲液中铂配合物与其降解产物，联用电喷雾质谱（ESI-MS／MS）检测，确证降解产物的结构。结果表明，SM54111溶液，在pH5．0～9．0时基本稳定，pH〈5．0时发生解离反应。证实该新型抗癌铂配合物SM54111在生理pH范围的溶液中稳定。在pH4．5时，以SM54111色谱峰面积计算，得到降解反应速率常数K=0．133h^-1，半衰期t1/2=5．6h。降解产物为母体化合物Pt—O键水解断裂的单齿水杨酸-Pt配合物，同时观察到Pt配合物的新裂解方式，可以经过亲柱攻击和重排反应同时脱去2个中性分子（C2H7N和H2），并证实其电离程度强烈依赖于电离原条件。该结果可为研究SM54111的药代动力学和药理学提供方法和参考。The stability of novel anticancer platinum complex in solution, named as cis-3,5-diisopropylsalicilyco-（1 R,2R-cyclodiamino）Pt （ Ⅱ ）, or SM 54111 for short, was investigated. The platinum complex was designed, synthesized, and characterized by element analysis, coupled inductively plasma mass spectrometry, gravitational thermal-differential thermal analysis, ultraviolet-visible absorption spectrometry, infrared specoscopy, fast atom bombment mass spectrometry and tH nuclear magnetic resonance, etc. High performance capillary electrophoresis-electrospray ionization-mass spectrometry（ HPCE-ESI-MSn） was employed to separate the platinum complex and the possible products of dissociation, to identify and quantify as well. It shows that this novel compound remains prototype at the range of pH 5.0 - 9.0. At pH value lower than 5.0, SM54111 disassociates by clearage producing monodentate platinum complex which was detected and identified with ESIMS^n. A type of novel cleavage was obtained by the compound tested, which indicated that the ionization rate depended on the ionization coalition. It was proved that SM54111 ＇s stability at physiological pH in solution was demonstrated and HPCE-ESI-MS/MS was a convenient and useful tool for the analysis of platinum complex. The results offered the method and reference for the study on the pharmacokinetics and pharmacology of SM54111.

关 键 词：高效毛细管电泳 电喷雾-质谱 铂配合物 稳定性 抗癌药物 

分 类 号：O657.63[理学—分析化学] O641.4[理学—化学]