키랄 HPLC를 이용한 라세미 케토프로펜의 광학분할

김소영; 이중기; 서성섭; 최민호; 박태진; 박달근; So-Young Kim; Joong Kee Lee; Sung-Sup Suh; Min-Ho Choi; Tae-Jin Park; Dalkeun Park

HWAHAK KONGHAK, Vol.39, No.6, 698-704, December, 2001

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키랄 HPLC를 이용한 라세미 케토프로펜의 광학분할

Optical Separation of Racemic Ketoprofen by Chiral High-Performance Liquid Chromatography

김소영, 이중기 ^{1, †}, 서성섭 , 최민호, 박태진 ¹, 박달근 ¹

홍익대학교 화학공학과, 서울 121-791
¹한국과학기술연구원 청정기술연구센터, 서울 136-791

So-Young Kim, Joong Kee Lee^{1, †}, Sung-Sup Suh , Min-Ho Choi, Tae-Jin Park¹, and Dalkeun Park¹

Department of Chemcal Engineering, Hongik University, Seoul 121-791, Korea
¹Clean Technology Research Center, Korea Institute of Science and Technology, Seoul 136-791, Korea

E-mail:

초록

케토프로펜은 비스테로이드 계통의 진통 및 소염제로서 류마티즘, 관절염 등을 위한 진통제나 해열제로 널리 사용되고 있다. 그러나 케토프로펜이 치료약으로 사용될 때 S-(+)-Ketoprofen이 주로 약리적 활성을 나타내고 R-(-)-Ketoprofen은 불활성이거나 오히려 부작용을 일으키는 문제점을 나타내고 있다. 본 연구에서는 케토프로펜 대장체(enantiomer)를 다양한 키랄 HPLC 칼럼을 이용하여 광학분할을 수행하면서 적합한 분리조건을 조사하였다. 고정상을 찾는 실험에서는 β-CD(β-cyclodextrin) BR(®)과 Kromasil(®) 칼럼을 이용하여 실험을 하였고, 이동상의 최적의 조성비를 찾는 실험도 수행하였다. 이 과정에서 라세미 Ketoprofen의 분리도는 사용된 키랄 고정상과 이동상의 조성비에 크게 영향을 받는다는 것을 알 수 있었다. 따라서 고정상으로는 Kromasil(®) 칼럼을 선택하고 이동상의 유속, 주입부피 그리고 주입농도가 라세미 Ketoprofen의 분리에 미치는 영향을 조사하였다. 실험결과 주입부피가 증가함에 따라서 분리도는 감소하였으나 이동상 유속이 증가함에 따라서 주입부피의 증가가 분리도에 미치는 영향은 점차 감소하는 것을 알 수 있었다.

Ketoprofen, a phenylpropionic acid derivative, is a non-steroidal anti-inflammatory drug(NSAID) that has analgesic, anti-inflammatory and antipyretic properties. Pharmacological activity has been attributed mainly to the S-(+)-enantiomer, while the R-(-)-enantiomer is either inactive or has side effect. The optical separation of Ketoprofen enantiomers was carried out by various chiral HPLC(chiral high-performance liquid chromatography) columns and most compatible separation conditions of Ketoprofen enantiomers were investigated. The resolution and enantio selectivity of Ketoprofen were found to be strongly influenced by the employed chiral stationary phases(CSPs) and composition of eluents. The employed chiral stationary phases(CSPs)in this study were β-CD BR(®) and Kromasil(®). The optimum compositionof eluent was obtained differently for stationary material phase. The effects of process variables such as flow rate, injection volume, and concentration of eluent on Ketoprofen enantiomers separation were investigated using Kromasil(®) columns. The resolution decreased with the increase of injection volume, however, the effect became insignificant at higher flow rate.

Keywords:Ketoprofen;Enantiomer;Separation;HPLC;Chiral Stationary Phase

[References]

현명호, "LC에 의한 광학 이성질체의 분리," 민음사, Seoul, Chap. 2 (1996)
Ravi B, Jurgen M, Biomed. Chromatogr., 12, 309 (1998)
Ahuja S, Appl. Technol., ACS (1997)
Cho OS, Kim OD, "Research on the Development of High Efficiency Separation System," KIST annual report UCE 1526-6343-6 (1999)
Song T, Suh SS, Choi MH, Kim YD, Lee JK, Park D, HWAHAK KONGHAK, 38(3), 373 (2000)
Armstrong DW, Anal. Chem., 59, 84A (1987)
Pirkle WH, Pochapsky TC, "Advances in Chromatography," J.C. Giddings, Ed., Marcel Dekker, New York, 27, Chap. 3 (1987)
Pirkle WH, Finn J, "Asymmetric Synthesis," Academic Press, New York, 1, Chap. 6 (1983)
Kim TJ, Lee JS, "A Study on the Separation, Analysis or Interpretation of Valuable Material," KIST The third year last report (1992)
Pirkle WH, Pochapsky TC, J. Am. Chem. Soc., 108, 5627 (1986)
Pirkle WH, Pochapsky TC, J. Am. Chem. Soc., 109, 5975 (1987)
De Jalon EG, Josa M, Campanero MA, Santoyo S, Ygartua P, J. Chromatogr. A, 143, 870 (2000)
Robert AC, Gilles C, Anh HN, Robert TF, J. Chromatogr. B, 175, 668 (1995)
Grubb NG, David WR, Stephen DH, J. Chromatogr. B, 237, 678 (1996)
Wechter WJ, Clin J, Pharmacol., 38, 1S-2S (1998)
Lederer K, Amtmann L, Vijaykumar S, Billiani J, J. Liq. Chromatogr., 13, 1849 (1990)
Gallagher W, Woodward C, Biopolymers, 28, 2001 (1989)
Gibbs S, Chu A, Lightfoot E, Root T, J. Phys. Chem., 93, 467 (1991)
Al-Duri B, McKay G, J. Chem. Technol. Biotechnol., 55, 245 (1992)
Seidel-Morgenstern A, Jacobson SC, Guiochon G, J. Chromatogr., 19, 637 (1993)

[Referenced By]

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[1] 현명호, "LC에 의한 광학 이성질체의 분리," 민음사, Seoul, Chap. 2 (1996)

[2] Ravi B, Jurgen M, Biomed. Chromatogr., 12, 309 (1998)

[3] Ahuja S, Appl. Technol., ACS (1997)

[4] Cho OS, Kim OD, "Research on the Development of High Efficiency Separation System," KIST annual report UCE 1526-6343-6 (1999)

[5] Song T, Suh SS, Choi MH, Kim YD, Lee JK, Park D, HWAHAK KONGHAK, 38(3), 373 (2000)

[6] Armstrong DW, Anal. Chem., 59, 84A (1987)

[7] Pirkle WH, Pochapsky TC, "Advances in Chromatography," J.C. Giddings, Ed., Marcel Dekker, New York, 27, Chap. 3 (1987)

[8] Pirkle WH, Finn J, "Asymmetric Synthesis," Academic Press, New York, 1, Chap. 6 (1983)

[9] Kim TJ, Lee JS, "A Study on the Separation, Analysis or Interpretation of Valuable Material," KIST The third year last report (1992)

[10] Pirkle WH, Pochapsky TC, J. Am. Chem. Soc., 108, 5627 (1986)

[11] Pirkle WH, Pochapsky TC, J. Am. Chem. Soc., 109, 5975 (1987)

[12] De Jalon EG, Josa M, Campanero MA, Santoyo S, Ygartua P, J. Chromatogr. A, 143, 870 (2000)

[13] Robert AC, Gilles C, Anh HN, Robert TF, J. Chromatogr. B, 175, 668 (1995)

[14] Grubb NG, David WR, Stephen DH, J. Chromatogr. B, 237, 678 (1996)

[15] Wechter WJ, Clin J, Pharmacol., 38, 1S-2S (1998)

[16] Lederer K, Amtmann L, Vijaykumar S, Billiani J, J. Liq. Chromatogr., 13, 1849 (1990)

[17] Gallagher W, Woodward C, Biopolymers, 28, 2001 (1989)

[18] Gibbs S, Chu A, Lightfoot E, Root T, J. Phys. Chem., 93, 467 (1991)

[19] Al-Duri B, McKay G, J. Chem. Technol. Biotechnol., 55, 245 (1992)

[20] Seidel-Morgenstern A, Jacobson SC, Guiochon G, J. Chromatogr., 19, 637 (1993)