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Simulated Moving Bed를 이용한 Bupivacaine 키랄분리 (1) Preparative Chromatography를 이용한 기본조건 결정
Chiral Separation of Bupivacaine by Simulated Moving Bed (1) Optical Separation Conditions for Preparative Chromatography
홍익대학교 화학공학과, 121-791 서울시 마포구 상수동 72-1 1한국과학기술연구원 나노환경기술연구센터, 136-791 서울시 성북구 하월곡동 39-1
Department of Chemical Engineering, Hongik University, 72-1, Sangsu-dong, Mapo-gu, Seoul 121-791, Korea 1Eco-Nano Technology Research Center, Korea Institute of Science and Technology, 39-1, Hawolgok-dong, Sungbuk-gu, Seoul 136-791, Korea
leejk@kist.re.kr
HWAHAK KONGHAK, December 2003, 41(6), 736-743(8), NONE
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Abstract
Racemate Bupivacaine의 키랄분리를 위한 크로마토그래피의 최적분리조건을 조사하였다. Kromasil® 키랄고정상에서 최적 이동상조성 성분은 n-hexane/2-propanol/acetic acid/triethylamine, 99/1/0.3/0.05(vol.%)이였다. 이동상 조성성분인 2-propanol의 부피비가 증가할수록 체류시간과 분리도가 동시에 감소되었다. 이동상 성분 중에서 미량으로 존재하는 triethylamine이 증가할수록 피크의 sharpness가 증가하고 체류시간 역시 감소하였다. 또한, acetic acid가 없으면, 크로마토그래피 광학분할이 불가능하였으며 부피 0.3%에서 분리도가 가장 높음을 확인할 수 있었다. 한편, 키랄의약품의 대량분리방법중의 하나인 SMB(simulated moving bed)크로마토그래피 시스템(직경 1.0 cm × 10 cm×8개 칼럼으로 구성)의 최적분리조건을 전산모사에 의해 구하였으며, 이를 실험으로 확인하였다. 그 결과 switching time 15분, feed의 유량 0.1 ml/min, desorbent 0.86 ml/min, raffinate 0.3 ml/min, extract 0.66 ml/min, recycle 1.0 ml/min일 때 100% 순도의 R-form과 S-form을 얻을 수 있었으며, 실험치와 전산모사치간의 오차는 ±2%이내였다.
The chiral separation of racemate Bupivacaine was carried out to find the optimum condition for chromatographic system. The optimum species and composition for mobile phase were n-hexane/2-propanol/acetic acid/triethylamine, 99/1/0.3/0.05(vol.%) in case Kromasil® chiral stationary phase was employed. The retention time and resolution decreased with the increase in the ratio of 2-propanol in the mobile phase. The sharpness of peak and retention time decreased, as the content of triethylamine increased. Without the existence of acetic acid, the chromatographic separation didn’t occur, and the resolution was the highest at the acetic acid volume ratio of 0.3%. The optimum condition of SMB (simulated moving bed) was determined by simulation and its results was compared with exprimental data from lab-scale SMB (10 mm ID×8 ea). Based on the SMB simulation and experimental results, 100% purity of R and S Bupivacaine were obtained and the error between the calculated and experimental value was within ±2%.
Keywords
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Tahraoui A, Watson DG, Skellern GG, Hudson SA, Petrie P, Faccenda K, J. Pharm. Biomedical Anal., 15, 251 (1996)
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Haarhoff PC, vanderLinde HJ, Anal. Chem., 38, 573 (1966)
Kim SY, Lee JK, Suh SS, Choi MH, Park TJ, Park D, HWAHAK KONGHAK, 39(6), 698 (2001)
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