Archives of Pharmacal Research

, Volume 40, Issue 3, pp 364–372 | Cite as

Determination of urazamide in pharmaceutical preparation with room temperature ionic liquid

  • Narae Seo
  • Yoo Rim Lee
  • Hyun Sun Park
  • Quoc-Ky Truong
  • Jae-Yong Lee
  • Hyun Kyu Chung
  • Yusung Choi
  • Byeonghee Kim
  • Sang Beom Han
  • Kyeong Ho KimEmail author
Research Article


A high performance liquid chromatographic method was developed and validated for the determination of urazamide in pharmaceutical preparation with novel green aqueous mobile phase modified with room temperature ionic liquids (RTILs). 1-Ethyl-3-methyl-imidazolium tetrafluoroborate ([EMIM][BF4]) was selected as a mobile phase additive to improve retention and avoid baseline disturbances at t0. Various mobile phase parameters such as cation moiety, chaotropic anion moiety, pH and concentration of RTILs were optimized to determine urazamide at the proper retention time. The assay was validated according to International Conference on Harmonization guidelines. The linearity of the calibration curve was good (r2 > 0.999). Intra-day precision varied between 0.50 and 1.23%. Relative standard deviations of inter-day precision ranged between 1.07 and 1.66%. Recoveries in tablets ranged between 99.7 and 101.2% and it was successfully applied to determine urazamide in pharmaceutical preparations.

Graphical Abstract


Very polar compound Urazamide Room temperature ionic liquids (RTILs) Reverse phase high performance liquid chromatography (RP-HPLC) 



This research was supported by 2014 Research Grant from Kangwon National University (No. 120140173).


  1. Armenta S, Garrigues S, Guardia M (2008) Green analytical chemistry. Trends Anal Chem 27:497–511CrossRefGoogle Scholar
  2. Berthod A, Ruiz-Ángel MJ, Carda-Broch S (2008) Ionic liquids in separation techniques. J Chromatogr A 1184:6–18CrossRefPubMedGoogle Scholar
  3. Carminati GM (1980) Pharmacology of 5-amino-4-imidazolcarboxamide ureidosuccinate (CARBAICA), a new gepatotrophic drug. Drug Exp Clin Res 6:471–489Google Scholar
  4. Cecchi T, Passamonti P (2009) Retention mechanism for ion-pair chromatography with chaotropic reagents. J Chromatogr A 1216:1789–1797CrossRefPubMedGoogle Scholar
  5. Chanoine F (1969) Clinical study of AICA orotate in hepatitis and cirrhosis. Acta Gastroenterol Belg 32:383–395PubMedGoogle Scholar
  6. Dolan JW (2008) Ion pairing—blessing or curse? LCGC Eur 21(5):258–263Google Scholar
  7. Farré M, Pérez S, Gonc C, Alves M, Alpendurada F, Barcelo D (2010) Green analytical chemistry in the determination of organic pollutants in the aquatic environment. Trends Anal Chem 29:1347–1362CrossRefGoogle Scholar
  8. Han D, Wang Y, Jin Y, Row KH (2011) Analysis of Some  -Lactam antibiotics using ionic liquids as mobile phase additives by RP-HPLC. J Chromatogr Sci 49(1):63–66CrossRefGoogle Scholar
  9. He L, Zhang W, Zhao L, Liu X, Jiang S (2003) Effect of 1-alkyl-3-methylimidazolium-based ionic liquids as the eluent on the separation of ephedrines by liquid chromatography. J Chromatogr A 1007:39–45CrossRefPubMedGoogle Scholar
  10. ICH Q2 (R1) (2005) ICH harmonised tripartite guideline: validation of analytical procedures: text and methodologyGoogle Scholar
  11. ICH Q3C (R4) (2009) ICH harmonised tripartite guideline: guideline for residual solventsGoogle Scholar
  12. Lee YR, Kim HJ, Seo N, Kim KH (2014) Development of alternative assay method without hazardous reagent, chloroform for urazamide tablets in Korean Pharmaceutical Codex. Yakhak Hoeji 58:125–128Google Scholar
  13. Pandey S (2006) Analytical applications of room-temperature ionic liquids: a review of recent efforts. Anal Chim Acta 556:38–45CrossRefPubMedGoogle Scholar
  14. Pham TP, Cho CW, Yun YS (2010) Environmental fate and toxicity of ionic liquids: a review. Water Res 44:352–372CrossRefPubMedGoogle Scholar
  15. Roda E, Sama C, Festi D (1979) Controlled clinical evaluation of the therapeutic effectiveness of AICA orotate in chronic hepatitis. Clin Ter 89:489–493PubMedGoogle Scholar
  16. Romero A, Santos A, Tojo J, Rodríguez A (2008) A toxicity and biodegradability of imidazolium ionic liquids. J Hazard Mater 151:268–273CrossRefPubMedGoogle Scholar
  17. Ruiz-Angel MJ, Carda-Broch S, Berthod A (2006) Ionic liquids versus triethylamine as mobile phase additives in the analysis of β-blockers. J Chromatogr A 1119(1–2):202–208Google Scholar
  18. Salar-García MJ, Ortiz-Martínez VM, Hernández-Fernándezm FJ, de Los Ríos AP, Quesada-Medina J (2017) Ionic liquid technology to recover volatile organic compounds (VOCs). J Hazard Mater 321:484–499CrossRefPubMedGoogle Scholar
  19. Snyder LR, Kirkland JJ, Dolan JW (2010) Introduction to modern liquid chromatography, 3rd edn. Wiley, Hoboken, pp 331–347Google Scholar
  20. Suh JH, Kim JH, Jung JH, Kim KH, Lee SG, Cho HD, Jung Y, Han SB (2013) Determination of thiamine in pharmaceutical preparations by reverse phase liquid chromatography without use of organic solvent. Bull Korean Chem Soc 34:1745–1750CrossRefGoogle Scholar
  21. Tang F, Tao L, Luo X, Ding L, Guo M, Nie L, Yao SJ (2006) Determination of octopamine, synephrine and tyramine in Citrus herbs by ionic liquid improved ‘green’ chromatography. J Chromatogr A 1125:182–188CrossRefPubMedGoogle Scholar
  22. Tian M, Liu J, Row KH (2009) Effect of ionic liquids as the mobile phase additives on the HPLC resolution of four active compounds from Sophora Flavescens Ait. Molecules 14(6):2127–2134CrossRefPubMedGoogle Scholar
  23. Tobiszewski M, Namieśnik J (2012) Direct chromatographic methods in the context of green analytical chemistry. Trends Anal Chem 35:67–73CrossRefGoogle Scholar
  24. Xiaohua X, Liang Z, Xia L, Shengxiang J (2004) Ionic liquids as additives in high performance liquid chromatography analysis of amines and the interaction mechanism of ionic liquids. Anal Chim Acta 519:207–211CrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2017

Authors and Affiliations

  1. 1.College of PharmacyKangwon National UniversityChuncheonKorea
  2. 2.College of PharmacyChung-Ang UniversitySeoulKorea

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