Chromatographic methods for the determination of butamirate citrate in presence of its degradation product

  • Ayat Mahmoud
  • Nahla sayedEmail author
  • Fekria Mosaad
  • Eglal Souaya
Original Paper


Two chromatographic methods were applied for the determination of butamirate citrate (BC) drug in the presence of its degradation product. Rapid resolution liquid chromatography (RRLC) Agilent SB-C18 (4.6 × 50 mm, 1.8 µm) column with mobile phase [0.2% triethyl amine buffer:acetonitrile (50:50 v/v)], pH 4.8 adjusted with phosphoric acid and ultraviolet detection at 222 nm was the first method. HPLC Promosil C18 (4.6 mm × 250 mm, 5 μm) column with mobile phase [0.05 M ammonium dihydrogen phosphate buffer:acetonitrile 50:50 (v/v)] with pH 5.4 and ultraviolet detection at 222 nm was the second method. These methods showed high sensitivity concerning linearity, accuracy, and precision over the range from 5 to 150 µg mL−1 and 1 to 150 µg mL−1 for RRLC and HPLC methods, respectively. The proposed methods were successfully applied for the determination of butamirate citrate (BC) in its commercial formulation (cough cut syrup). The International Conference on Harmonization guidelines (ICH) were adopted for methods’ validation with respect to linearity, LOD, LOQ, precision and specificity. Moreover, to establish stability-indicating capability of the proposed methods, the kinetics of degradation of BC were studied in aqueous alkaline and acidic solution. The thermodynamic parameters of activation (enthalpy, free energy and entropy) were determined for acidic degradation reaction and half-life times could also be estimated.


Butamirate citrate Kinetic degradation Stability testing RRLC HPLC 



  1. Ahmed M, Alaa E, Samy E (2011) Development, application and validation of RP-HPLC method for the simultaneous determination of butamirate citrate and its main degradation product in pharmaceutical dosage forms. R Soc Chem 3:1643–1651Google Scholar
  2. Alok KP, Rahman MM, Syeda S, Anita P, Al Arif MH, Tazul I, Sarder A, Mohammed R (2011) Development and validation of a new stable HPLC method for the assay of butamirate citrate in pharmaceutical formulations. Adv Nat Appl Sci 5(2):75–84Google Scholar
  3. Ayman AG, Ragaa ES, Alaa SA (2008) Spectrophotometric determination of some anti-tussive drugs and its applications to pharmaceutical formulations. Anal Chem 7(10):757–767Google Scholar
  4. Brayfield A (2017) Martindale: The Complete Drug Reference, 39th ed. PhP, Pharmaceutical Press, London, UKGoogle Scholar
  5. Doi I, Altesor C, Knochen M (1996) Application of an optical compensation method to the simultaneous determination of butamirate citrate and sodium benzoate by derivative spectrophotometry in the ultraviolet. J Quim Anal 15(2):148–153Google Scholar
  6. Galliard JA, Ritter C (1997) Use of simulated liquid chromatography-diode array detection data for the definition of a guide curve in peak purity assessment by spectral comparison. J Chromatogr A 786:1–11CrossRefGoogle Scholar
  7. ICH (2005) Validation of analytical procedures. In: Proceeding of the international conference on harmonization, Geneva, Q2 (R1)Google Scholar
  8. Kenneth AC, Gordon LA, Lloyd K (1979) Chemical stability of pharmaceuticals, a handbook for pharmacists. Wiley, New York, p 20Google Scholar
  9. Malliou ET, Antoniou CG, Koundourellis JE (2003) Determination of butamirate citrate in cough preparations by derivative UV spectrophotometry and high performance liquid chromatography. Anal Sci 19(4):563–568CrossRefGoogle Scholar
  10. Mohamed H (2011) Development and validation of a stability indicating HPLC method for the estimation of butamirate citrate and benzoic acid in pharmaceutical products. J Chromatogr Sep Tech 2:2Google Scholar
  11. Nichola CG, Jonathan BC (2012) Thermodynamic studies for drug design and screening. Expert Opin Drug Discov 7(4):299–314CrossRefGoogle Scholar
  12. Reviewer guidance’ validation of chromatographic methods, November 1994Google Scholar
  13. Robyn C (2006) Achieving high performance with rapid resolution HT (1.8um) columns. Agilent technologies, Woolley Online Application Engineer, June 14Google Scholar
  14. Sonia TH, Asmaa AE, Marwa AF (2011a) Development and validation of RP-HPLC stability-indicating methods for the determination of butamirate citrate and sodium cromoglycate. J Chem Pharm 3(6):243–258Google Scholar
  15. Sonia TH, Asmaa AE, Marwa AF (2011b) Validated stability-indicating derivative and derivative ratio methods for the determination of some drugs used to alleviate respiratory tract disorders and their degradation products. Drug Test Anal 3(5):306–318CrossRefGoogle Scholar
  16. Through website (2014) Accessed 29 Feb 2014
  17. USP (2018) 41th ed and the national formulary (NF). 36th ed. USA: US Pharmacopeial Convention Rockville MDGoogle Scholar

Copyright information

© Institute of Chemistry, Slovak Academy of Sciences 2019

Authors and Affiliations

  • Ayat Mahmoud
    • 1
  • Nahla sayed
    • 1
    Email author
  • Fekria Mosaad
    • 1
  • Eglal Souaya
    • 2
  1. 1.National Organization for Drug Control and Research (NODCAR)GizaEgypt
  2. 2.Chemistry Departments, Faculty of ScienceAin Shams UniversityCairoEgypt

Personalised recommendations