KSBB Journal

The Korean Society for Biotechnology and Bioengineering (한국생물공학회)
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Monitoring of the Optical Purity for Levothyroxine Sodium in Pharmaceuticals Using Crown Ether Derived Chiral Columns

크라운 에테르에서 유도된 키랄 컬럼을 사용한 레보티록신 나트륨 의약품의 광학순도 모니터링

  • 전소희 (조선대학교 약학대학 약학과) ;
  • 이원재 (조선대학교 약학대학 약학과)
  • Received : 2010.09.10
  • Accepted : 2010.10.23
  • Published : 2010.10.31
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Abstract

L-Thyroxine possessing a chiral center, the naturally occurring thyroid hormone has been used for the treatment of thyroid dysfunctions and marketed as levothyroxine (L-thyroxine) sodium salt. In this study, after extraction of levothyroxine tablet as a pre-treatment process, direct enantiomer separation of thyroxine on crown ether derived chiral columns for determination of optical purity was performed using reversed mobile phase with acid additive. The chromatographic method developed in this study was applied in the determination of optical purity of several current domestic and foreign commercialized levothyroxine tablets. Optical purity values of these commercialized L-thyroxine sodium tablets except one were higher than 99 percents.

크라운 에테르로부터 유도된 키랄고정상에서 역상용매를 이동상으로 사용하여 국내외에서 시판되고 있는 광학이성질체 의약품인 레보티록신 나트륨의 광학순도 측정을 위한 새로운 직접적인 광학분리 분석법을 개발하여 매우 좋은 결과를 얻었다 ($\alpha$ = 2.15, Rs = 4.05). 시판하고 있는 레보티록신 나트륨의 광학순도를 키랄고정상을 이용하여 직접적인 광학분리방법으로 측정하는 실험은 현재까지 한 편의 연구결과 외에는 보고되어 있지 않는데 [4] 본 연구에서 새롭게 개발한 전처리과정과 HPLC 분석조건을 이용하여 현재 국내외에서 판매되고 있는 레보티록신 나트륨 주성분의 의약품 정제의 광학순도를 측정하였다. 레보티록신 나트륨의 광학순도를 측정한 광학분리 실험결과에서 하나의 제품을 제외하고는 99% 이상의 높은 광학순도를 보여주고 있음을 확인할 수 있었다. 본 연구의 편리하고 용이한 신규 광학분리 분석법이 국내외에서 상용되는 레보티록신 나트륨 제품의 품질 확인과 양질의 키랄의약품을 개발하고 제품을 관리하는데 매우 도움이 되리라 기대한다.

Keywords

Acknowledgement

Supported by : 한국연구재단

References

  1. Francotte, E. and W. Lindner, (Ed.) (2006) Chirality in Drug Research. Wiely-VCH, Weinheim.
  2. Bantle, J., J. Oppenheimer, H. Schwartz, D. Hunninghake, J. Probstfield and R. Hanson (1981) TSH response to TRH in euthyroid, hypercholesterolemic patients treated with graded doses of dextrothyroxine. Metabolism 30: 63-66. https://doi.org/10.1016/0026-0495(81)90220-1
  3. Abou-Basha, L. I. and H. Y. Aboul-Enein (1995) Enantiomeric separation and optical purity determination of thyroxine enantiomers in bulk and pharmaceutical formulations. Pharm. Acta Helv. 70: 237-240. https://doi.org/10.1016/0031-6865(95)00024-4
  4. Gika, H., M. Lammerhofer, I. Papadoyannis and W. Lindner (2004), Direct separation and quantitative analysis of thyroxine and triiodothyronine enantiomers in pharmaceuticals by high-performance liquid chromatography J. Chromatogr. 800: 193-201. https://doi.org/10.1016/j.jchromb.2003.07.005
  5. Aboul-Enein, H. Y., I. Ali, M. H. Hyun, Y. J. Cho, and J. S. Jin (2002) Effect of acidity on the enantiomeric resolution of thyroxine and tocainide by HPLC on a (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid column J. Biochem. Bioph. Methods. 54: 407-413. https://doi.org/10.1016/S0165-022X(02)00142-2
  6. Jin, J. Y., C.-S. Baek, and W. Lee (2007) Development of a validated HPLC method for the simultaneous determination of D- and L-thyroxine in human plasma. Bull. Kor. Chem. Soc. 28: 1070-1072. https://doi.org/10.5012/bkcs.2007.28.6.1070
  7. Hyun, M.H., J. S. Jin, and W. Lee (1998) Liquid chromatographic resolution of racemic amino acids and their derivatives on a new chiral stationary phase based on crown ether. J. Chromatogr. A 822: 155–161.
  8. Lee, W., J. Y. Jin and C.-S. Baek (2005) Comparison of enantiomer separation on two chiral stationary phases derived from (+)-18-crown-6-2,3,11,12-tetracarboxylic acid of the same chiral selector. Microchemical Journal 80: 213-217. https://doi.org/10.1016/j.microc.2004.07.010
  9. Jin, J. Y., W. Lee, and M. H. Hyun (2006) Development of the antipode of the covalently-bonded crown ether type chiral stationary phase for the advantage of the reversal of elution order. J. Liq. Chrom. & Rel. Tech. 29: 841-848. https://doi.org/10.1080/10826070500531102
  10. Jin, J. Y. and W. Lee (2007) Liquid chromatographic enantiomer resolution of N-hydrazide derivatives of 2-aryloxypropionic acids on a crown ether derived chiral stationary phase, Chirality 19: 120-123. https://doi.org/10.1002/chir.20354
  11. Lee, T., W. Lee, M. H. Hyun, and J. H. Park (2010) Enantioseparation of native $\alpha$-amino acids on an 18- crown-6-tetracarboxylic acid-bonded silica by capillary electrochromatography. J. Chromatogr. A 1217: 1425-1428.
  12. Perry, J. A., J. D. Rateike, and T. J. Szczerba (1987) Eluting trace components before major constituents : I. Sensitivity enhancement in analytical determinations of optical purity. J. Chromatogr. 389: 57-64. https://doi.org/10.1016/S0021-9673(01)94410-3
  13. Jin, D., M. Zhang, S. Jin, M. Lee, G. Song, G. Back and Y. Lee (2007) Enantioselective resolution of thyroxine hormone by high-performance liquid chromatography utilizing a highly fluorescent chiral tagging reagent. Chirality 19: 625-631. https://doi.org/10.1002/chir.20414