YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Development of Analytical Method for Ambroxol Hydrochloride and Clenbuterol Hydrochloride Formulation in Korean Pharmaceutical Codex

고시수재 의약품 중 암브록솔염산염 및 클렌부테롤염산염 함유 제제의 함량 시험법 개선

  • Lee, Tae-Woong (Hazardous Substances Analysis Division, Daejeon regional Korea Food & Drug Administration) ;
  • Jeong, Rae-Seok (Hazardous Substances Analysis Division, Daejeon regional Korea Food & Drug Administration) ;
  • Park, Soo-Jin (Hazardous Substances Analysis Division, Daejeon regional Korea Food & Drug Administration) ;
  • Choi, Lan (National Institute of Food and Drug Safety Evaluation, Osong Health Technology Administration Complex) ;
  • Shim, Young-Hun (National Institute of Food and Drug Safety Evaluation, Osong Health Technology Administration Complex) ;
  • Choi, Bo-Kyung (National Institute of Food and Drug Safety Evaluation, Osong Health Technology Administration Complex) ;
  • Kwak, Hyo-Sun (Hazardous Substances Analysis Division, Daejeon regional Korea Food & Drug Administration)
  • 이태웅 (대전지방식품의약품안전청 유해물질분석과) ;
  • 정래석 (대전지방식품의약품안전청 유해물질분석과) ;
  • 박수진 (대전지방식품의약품안전청 유해물질분석과) ;
  • 최란 (식품의약품안전평가원 의약품규격연구과) ;
  • 심영훈 (식품의약품안전평가원 의약품규격연구과) ;
  • 최보경 (식품의약품안전평가원 의약품규격연구과) ;
  • 곽효선 (대전지방식품의약품안전청 유해물질분석과)
  • Received : 2014.04.30
  • Accepted : 2014.06.05
  • Published : 2014.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

The Korean Pharmaceutical Codex (KPC) analytical method of ambroxol hydrochloride and clenbuterol hydrochloride formulation is complicated and needed to carry out multiple processes during the test. To improve the low efficiency of analytical procedure that makes pharmaceutical laboratory consume much time and high cost to conduct the test of this formulation, this study was performed for simplifying the pretreatment process and optimizing conditions of the HPLC assay. The analytical procedure using HPLC was developed to establish analytical specification for ambroxol hydrochloride and clenbuterol hydrochloride formulations. The newly developed analytical method has good linearity ($R^2$ >0.999), specificity, precision (RSD<1.0%) and the recovery ranges of 98.50~101.84% for ambroxol, 98.29~101.35% for clenbuterol syrup and 98.66~101.71% for clenbuterol tablets. The LOQs were 0.204 ${\mu}g/ml$ for ambroxol, 0.021 ${\mu}g/ml$ for clenbuterol syrup and 0.073 ${\mu}g/ml$ for clenbuterol tablets. The new method was performed with commercially available samples to confirm analytical conditions and validated to be suitable for saving time and cost to control the quality of routine manufactured products. This analytical method will be used for revising the monograph of ambroxol hydrochloride and clenbuterol hydrochloride formulation in next supplement of KPC.

Keywords

References

  1. 식품의약품안전처 고시 : 대한민국약전외 의약품 기준 (2013).
  2. 대한민국약전 10개정 : 의약품등 시험방법 밸리데이션 가이드라인 (2013).
  3. Hasegawa, I., Niisato, N., Iwasaki, Y. and Marunaka, Y. : Ambroxol-induced modification of ion transport in human airway Calu-3 epithelia. Biochem. Biophys. Res. Commun. 343, 475 (2006). https://doi.org/10.1016/j.bbrc.2006.03.009
  4. Yamada, T., Takemura, Y., Niisato, N., Mitsuyama, E., Iwasaki, Y. and Marunaka, Y. : Action of N-acylated ambroxol derivatives on secretion of chloride ions in human airway epithelia. Biochem. Biophys. Res. Commun. 380, 586 (2009). https://doi.org/10.1016/j.bbrc.2009.01.122
  5. Lee, H. J., Joung, S. K., Kim, Y. G., Yoo, J.-Y. and Han, S. B. : Bioequivalence assessment of ambroxol tablet after a single oral dose administration to healthy male volunteers. Pharmacol. Res. 49, 93 (2004). https://doi.org/10.1016/j.phrs.2003.07.011
  6. Cho, Y., Jang, Y. Y., Han, E. S. and Lee, C. S. : The inhibitory effect of ambroxol on hypochlorous acid-induced tissue damage and respiratory burst of phagocytic cells. Eur. J. Pharmacol. 383, 83 (1999). https://doi.org/10.1016/S0014-2999(99)00585-3
  7. Martin, P., Soubrie, P. and Simon, P. : Does a single priming injection of clenbuterol alter behavioral response to ${\beta}$-adrenoceptor agonists and antagonists in mice through a timedependent process. Eur. J. Pharmacol. 115, 91 (1985). https://doi.org/10.1016/0014-2999(85)90588-6
  8. Kazanietz, M. G., Gutkind, J. S. and Enero, M. A. : Interaction between ${\beta}2$- and ${\alpha}2$-adrenoceptor responses in the vascular system: effect of clenbuterol. Eur. J. Pharmacol. 130, 119 (1986). https://doi.org/10.1016/0014-2999(86)90190-1
  9. Re, G., Badino, P., Girardi, C. and Carlo, F. D. : Effects of a ${\beta}2$-agonist (clenbuterol) on cultured human (CG-5) breast cancer cells. Pharmacol. Res. 26, 377 (1992). https://doi.org/10.1016/1043-6618(92)90236-5
  10. Yamashita, J., Nagase, H., York, D. A. and Bray, G. A. : Effects of clenbuterol, a ${\beta}2$-Adrenoceptor agonist, on Macronutrient selection in rats. Physiology & Behavior 56, 251 (1994). https://doi.org/10.1016/0031-9384(94)90192-9
  11. Fabre, J., Bousquet, J., Lebel, B., Jirou-Najou, J. L., Cluzel, M., Godard, P. and Michel, F. B. : Anti-allergic activity of an oral beta-2 agonist, clenbuterol. J. Allergy Clin. Immunol. 81, 311 (1988).
  12. Elfinger, M., Geiger, J., Hasenpusch, G., Uzgun, S., Sieverling, N., Aneja, M. K., Maucksch, C. and Rudolph, C. : Targeting of the $\beta2$-adrenoceptor increases nonviral gene delivery to pulmonary epithelial cells in vitro and lungs in vivo. J. Controlled Release 135, 234 (2009). https://doi.org/10.1016/j.jconrel.2009.01.012
  13. 식품의약품안전처 : 2013 식품의약품통계연보 (2013).
  14. ICH : Validation of Analytical Procedures : Text and Methodology Q2(R1) (2005).
  15. 식품의약품안전청 : 대한민국약전 개정안 작성지침 (2013).
  16. FDA, Center for Drug Evaluations and Research, Guidance for Industry-Extended release oral dosage forms : Development, evaluations and application of in vitro/in vivo correlation (1997).
  17. United States Pharmacopoeial Convention, Inc. : The United States Pharmacopeia 35th (2009).
  18. Society of Japanese Pharmacopoeia : The Japanese Pharmacopoeia 16th (2011).
  19. 식품의약품안전처 고시 : 의약품동등성시험기준 (2013).
  20. 대한민국약전 10개정 : 일반시험법 (2013).
  21. Rote, A. R. and Kande, S. K. : Development of HPTLC method for determination of cefpodoxime proxetil and ambroxol hydrochloride in human plasma by liquid-liquid extraction. Pharm. Methods 2, 242 (2011). https://doi.org/10.4103/2229-4708.93394
  22. Dharuman, J., Vasudhevan, M. and Ajithlal, T. : High performance liquid chromatographic method for the determination of cetirizine and ambroxol in human plasma and urine-A boxcar approach. J. Chromatogr. B 879, 2624 (2011). https://doi.org/10.1016/j.jchromb.2011.07.024
  23. Shaikh, K. A., Patil, S. D. and Devkhile, A. B. : Development and validation of a reversed-phase HPLC method for simultaneous estimation of ambroxol hydrochloride and azithromycin in tablet dosage form. J. Pharm. Biomed. Anal. 48, 1481 (2008). https://doi.org/10.1016/j.jpba.2008.09.031
  24. Hadad, G. M., El-Gindy, A. and Mahmoud, W. M. M. : HPLC and chemometrics-assisted UV-spectroscopy methods for the simultaneous determination of ambroxol and doxycycline in capsule. Spectrochim. Acta, Part A 70, 655 (2008). https://doi.org/10.1016/j.saa.2007.08.016
  25. Bazylak, G. and Nagels, L. J. : Simultaneous high-throughput determination of clenbuterol, ambroxol and bromhexine in pharmaceutical formulations by HPLC with potentiometric detection. J. Pharm. Biomed. Anal. 32, 887 (2003). https://doi.org/10.1016/S0731-7085(03)00191-2
  26. Abdel-Ghani, N. T. and Hussein, S. H. : Determination of ambroxol hydrochloride in pure solutions and some of its pharmaceutical preparations under batch and FIA conditions. Il Farmaco 58, 581 (2003). https://doi.org/10.1016/S0014-827X(03)00045-4
  27. Trejo, F. M., Leon, S. V., Medina, A. E. and Tolentino, R. G. : Application of high-performance liquid chromatography-UV detection to quantification of clenbuterol in bovine liver samples. JFDA 21, 414 (2013).
  28. Furusawa, N. : An isocratic solvent-free mobile phase HPLC-PDA analysis of clenbuterol and ractopamine. Int. J. Chem. Anal. Sci. 4, 169 (2013). https://doi.org/10.1016/j.ijcas.2013.07.002
  29. Liu, B., Yan, H., Qiao, F. and Geng, Y. : Determination of clenbuterol in porcine tissues using solid-phase extraction combined with ultrasound-assisted dispersive liquid-liquid microextraction and HPLC-UV detection. J. Chromatogr. B 879, 90 (2011). https://doi.org/10.1016/j.jchromb.2010.11.017