目的建立氟比洛芬、班布特罗等14种手性药物的高效液相色谱手性拆分方法。方法利用chiralpak AD手性柱,以正己烷-乙醇为流动相基本成分,调整两者不同比例和添加不同量的三氟乙酸(TFA)或三乙胺(TEA),对氟比洛芬、酮洛芬、扁桃酸、氟伐他汀、邻氯扁桃酸、依托度酸、布洛芬、萘普生等8个酸性手性药物,和班布特罗、普罗帕酮、西替利嗪、非洛地平、尼群地平、尼莫地平等6个碱性手性药物进行了拆分研究。考察了流动相中正己烷和乙醇的比例、TFA或TEA添加量对手性分离的影响。结果在一定色谱条件下,被检样品中大部分手性药物的两个对映体实现了较好分离。在正己烷-乙醇流动相系统中,正己烷含量为90%～99%,TFA含量为0.1%～0.3%的条件下,氟比洛芬、酮洛芬、扁桃酸、氟伐他汀、邻氯扁桃酸、依托度酸、布洛芬两对映体间的分离度(Rs)分别为11.0,12.5,4.70,5.30,1.90,1.50,1.60。但萘普生的两个对映体在上述各条件下始终未获得分离。在正己烷-乙醇-TEA(40∶60∶0.05)流动相体系中,逐渐提高正己烷比例和TEA含量,普罗帕酮、西替利嗪、班布特罗、尼群地平、非洛地平的两个对映体色谱峰达到基线分离,分离度分别为8.20,3.0,1.90,1.90和1.60。但尼莫地平始终未获分离。结论建立的手性HPLC能有效拆分氟比洛芬、班布特罗等12个手性药物对映体。

OBJECTIVE To establish chiral HPLC methods for the enantiomeric separation of fourteen drugs,such as flurbiprofen and bambuterol.METHODS Enantiomeric separation of fourteen compounds was performed on a chiralpak AD column.The chiral separation of eight acid compounds(flurbiprofen,ketoprofen,mandelic acid,fluvastatin,o-chloro mandelic acid,etodolac,ibuprofen and naproxen)and six basic compounds(bambuterol,propafenone,cetirizine,nitrendipine,felodipine and nimodipine)was investigated with the mobile phase of consisting n-hexane,ethanol and different proporation of trifluoroacetic acid(TFA)or triethylamine(TEA).The mobile phase compositions were systematically investigated to obtain the optimal chromatographic profile.RESULTS The ratio of n-hexane/ethanol and the contents of acid or basic additive were the primary influencing factors for chiral separation.The good resolutions of acidic compounds flurbiprofen,ketoprofen,mandelic acid,fluvastatin,o-chloro mandelic acid,etodolac and ibuprofen were obtained with the resolution factors of 11.0,12.5,4.70,5.30,1.90,1.50 and 1.60 respectively,while the content of n-hexane was 90%～99% and TFA content was 0.1%～0.3%.The separation of enantiomers of naproxen wasn't obtained.After gradually enhanced the ratio of n-hexane and the content of TEA in mobile phase of n-hexane-ethanol-TEA,the baseline enantioseparation was obtained for basic compounds propafenone,cetirizine,bambuterol,nitrendipine and felodipine,and their resolution was 8.20,3.0,1.90,1.90 and 1.60 respectively,but nimodipine couldn't be separated.CONCLUSION Twelve compounds are separated successfully on the chiralpak AD column under suitable chromatographic conditions.