CHIRALPAK AD柱在14种药物手性分离中的应用

Application of CHIRALPAK AD Column to Chiral Separation of Fourteen Drugs

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 investi- gated 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 nhexane 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.