Spectrophotometric Method for the Determination of Bromhexine-HCl in Bulk and Dosage Forms Via Azo Dye Formation with 4'-Chloro-4-Hydroxychalcone

Muner Hamed; Kameran Hussein; Abdul Majeed Ahmed

doi:10.18596/jotcsa.1811233

Spectrophotometric Method for the Determination of Bromhexine-HCl in Bulk and Dosage Forms Via Azo Dye Formation with 4'-Chloro-4-Hydroxychalcone

Abstract

Bromhexine-HCl (BHH) can be determined in pharmaceutical formulations and in its pure form using a simple, quick, and affordable spectrophotometric approach. New organic reagents are prepared for the investigation, and 4'-Chloro-4-hydroxychalcone (4-CHC) is chosen as the best reagent. A second stage in the process involves diazotizing BHH, which contains an (NH2) group, using NaNO2, and then reacting with the (4-CHC) reagent to form a stable, colored complex in basic media. The wavelength at which this combination shows the highest absorbance is 436 nm. The discovered method has a molar absorptivity of 1.9063×104 L /mol .cm and a linearity range of (2.0 to 18) μg/mL. The relative standard deviation (RSD) was less than 0.985%. Additionally, 0.280 μg/mL was shown to be the limit of detection (LOD). With a minimum recovery rate of 99.4%, the approach effectively identified the pharmaceutical product containing Bromhexine (Solvodin@ tablets).

Keywords

Thanks

The authors would like to express their sincere thanks to Dr. Ali for his valuable assistance and guidance during this research work.

References

1. Bhagat A, Rachana R. Bromhexine: A comprehensive review. Int J Biol &Medical Res [Internet]. 2018;9(3):6455–9. Available from: .
2. Talukdar A, Sarkar D, Sarkar D. Bromhexine: Into the spotlight. In: Viral, Parasitic, Bacterial, and Fungal Infections [Internet]. Elsevier; 2023. p. 719–31. Available from: .
3. Tolouian R, Mulla ZD, Jamaati H, Babamahmoodi A, Marjani M, Eskandari R, et al. Effect of bromhexine in hospitalized patients with COVID-19. J Investig Med [Internet]. 2023 Oct 12;71(7):691–9. Available from: .
4. Strózik M, Strzebońska M, Skiba K, Tatara W. Development and validation of the analytical methods for determination of bromhexine hydrochloride and related impurities in novel orodispersible tablets. Acta Pol Pharm - Drug Res [Internet]. 2022 Nov 21;79(4):455–64. Available from: .
5. Pharmacopoeia B.: The Stationery Office. Vol. I. London; 2014. 125–127 p.
6. Lad M V., Jain V, Raj H. A review of analytical methods for determination bromhexine hydrochloride in pharmaceutical and biological samples. Pharma Tutor Mag [Internet]. 2014;2(11):35–41. Available from: .
7. Al-Hafidh HAS, Albadgari RM. Development of a spectrophotometric method for the assay of bromhexine hydrochloride in its pure form and in its pharmaceutical preparations using diazotization-coupling reaction. J Teknol [Internet]. 2025 Aug 22;87(5):999–1006. Available from: .
8. Kareem NK, Thani MZ, Al-Rawi KF. New microextraction methods for the evaluation of bromhexine HCl in pure and pharmacological formulations. Egypt J Chem [Internet]. 2022 Oct 5;65(4):209–19. Available from: .

9. Sultan SH, Majed ZW. Spectrophotometric determination of bromhexine hydrochloride by diazotization and coupling method in its pharmaceutical preparations. Iraqi J Sci [Internet]. 2020 Sep 29;61(9):2172–81. Available from: .
10. Mohammed SA, Almukhtar RF. Indirect spectrophotometric method for determination of bromhexine-HCl in pharmaceutical preparations. Rafidain J Sci [Internet]. 2018;27(2):116–26. Available from: .
11. Siddappa K, Hanamshetty PC. Spectrophotometric quantitative determination of bromhexine hydrochloride in bulk and pharmaceutical dosage form using PDEAB reagent. Chem Sci Trans [Internet]. 2016 Jul 30;5(3). Available from: .
12. Narayana A, Rao CN, Sivakumar K. Spectrophotometric determination of bromhexine using charge transfer complex reaction. Indian J Adv Chem Sci. 2015;3(2):128–32.
13. Rele R V. Simultaneous UV-spectrophotometric estimation of bromhexine hydrochloride and salbutamol sulphate by area under curve method in combined dosage form. Der Pharm Sin [Internet]. 2015;6(5):8–14. Available from: .
14. Tantawy MA, Abdulla SA, Mohamed OY, Abou Al-Alamein AM. Normal-phase TLC and gradient reversed-phase HPLC for the simultaneous determination of enrofloxacin and bromhexine HCl in presence of two of their official impurities. J Chromatogr Sci [Internet]. 2023 Jul 9;61(6):546–51. Available from: .
15. Jain V, Sharma MC. Validated RP-HPLC method for determining the levels of bromhexine HCl, chlorpheniramine maleate, dextromethorphan HBr and guaiphenesin in their pharmaceutical dosage forms. J Taibah Univ Sci [Internet]. 2016 Jan 16;10(1):38–45. Available from: .
16. Rao N, Gawde KD. Method development and force degradation studies for simultaneous estimation of salbutamol sulfate, etofylline and bromhexine hydrochloride in pharmaceutical dosage form using reversed-phase high-performance liquid chromatography method. Asian J Pharm Clin Res [Internet]. 2018 Aug 7;11(8):378–82. Available from: .
17. Joshi H, A. S, Patel J, Patel S. Development and validation of analytical method for simultaneous estimation of bromhexine HCl and enrofloxacine in combined pharmaceutical dosage form. Eurasian J Anal Chem [Internet]. 2017 Oct 26;12(8):1631–8. Available from: .
18. Obeid M, Allous I, Hirbali J. Validated PR-HPLC method for determination of bromhexine hydrochloride, terbulaine sulfate and guaiphenesine in pharmaceutical dosage forms. Asian J Pharm Anal Med Chem [Internet]. 2016;4(2):69–73. Available from: .
19. Kong D, Han L, Wang Z, Jiang L, Zhang Q, Wu Q, et al. An electrochemical sensor based on poly(procaterol hydrochloride)/carboxyl multi-walled carbon nanotube for the determination of bromhexine hydrochloride. RSC Adv [Internet]. 2019;9(21):11901–11. Available from: .
20. Mika J, Moreira JC, Nemeckova A, Zima J, Barek J, Dejmkova H. Determination of bromhexine at a glassy carbon paste electrode using differential pulse voltammetry and flow injection analysis with amperometric detection. Monatshefte für Chemie - Chem Mon [Internet]. 2015 Aug 8;146(8):1211–5. Available from: .
21. Abdel-Ghani NT. Potentiometric flow injection analysis of bromhexine hydrochloride and its pharmaceutical preparation using conventional and coated wire ion-selective electrodes. Sci Pharm [Internet]. 2006;74(3):121–35. Available from: .
22. Oliva DC, Torres Vélez K, Luisa A, Vázquez R. Simultaneous determination of bromhexine and amoxicillin in pharmaceutical formulations by capillary electrophoresis article. Chem Soc [Internet]. 2011;55(2):79–83. Available from: .
23. Taha EA. Validated ATR-FTIR method for quantitative simultaneous estimation of terbutaline sulfate, guaiphenesin and bromhexine hydrochloride, in bulk and pharmaceutical dosage form. Egypt J Chem [Internet]. 2023 Mar 16;66(12):155–61. Available from: .
24. Jiang Q, Nie F, Lu J. Chemiluminescence determination of bromhexine hydrochloride with morin as chemiluminescent reagent. Luminescence [Internet]. 2008 Jan 4;23(1):32–6. Available from: .
25. Atiyah A, Hussein K, Ahmed AM. Spectrophotometric determination of meloxicam in pure form and its pharmaceutical formulation following azo dye formation with 4-nitroaniline. J Turkish Chem Soc Sect A Chem [Internet]. 2024 Dec 3;11(4):1461–72. Available from: .
26. Atiyah AM, Ahmed A, Alrashidy M, Majeed A, Ahmed K. Spectrophotometric determination of meloxicam in pure form and its pharmaceutical preparations via oxidative coupling reaction. Bull Pharm Sci Assiut Univ [Internet]. 2024;47(2):1049–62. Available from: .
27. Younes SR, Ahmed ID. Spectrophotometric determination of bromhexine via ion-pair complex formation with Eosin Y : Method development , validation , and pharmaceutical application. https://biojournals.us/index.php/AJBP/article/view/1415/1192 [Internet]. 2025;2(9):1–9. Available from: .
28. Mohammed SA, Almukhtar RF. Spectrophotometric assay of bromhexine hydrochloride in pure and in pharmaceutical dosage forms by diazometry coupling reaction. J Educ Sci [Internet]. 2013;26(5):197–209. Available from: .
29. Susmitha K, Thirumalachary M, Venkateshwarlu G. Spectrophotometric determination of bromhexine HCl in pure and pharmaceutical forms. ISRN Anal Chem [Internet]. 2013 Aug 12;2013(1):861851. Available from: .
30. Othman N, Omer SA. Spectrophotometric determination of bromhexine hydrochloride by azo-dye formation reaction. J Educ Sci [Internet]. 2009 Mar 1;22(1):19–31. Available from: .

Details

Primary Language

English

Subjects

Analytical Spectrometry

Journal Section

Research Article

Authors

Muner Hamed ^*
0009-0004-9160-1449
Iraq

Kameran Hussein
0009-0004-5961-9673
Iraq

Abdul Majeed Ahmed
0000-0003-2013-2353
Iraq

Publication Date

January 15, 2026

Submission Date

October 27, 2025

Acceptance Date

December 17, 2025

Published in Issue

Year 2026 Number: 2026-1

DOI

https://doi.org/10.18596/jotcsa.1811233

IZ

https://izlik.org/JA85FG38YH

Cite

RIS / Bibtex

APA

Hamed, M., Hussein, K., & Ahmed, A. M. (2026). Spectrophotometric Method for the Determination of Bromhexine-HCl in Bulk and Dosage Forms Via Azo Dye Formation with 4’-Chloro-4-Hydroxychalcone. Journal of the Turkish Chemical Society Section A: Chemistry, 2026-1, 1-15. https://doi.org/10.18596/jotcsa.1811233

AMA

1.Hamed M, Hussein K, Ahmed AM. Spectrophotometric Method for the Determination of Bromhexine-HCl in Bulk and Dosage Forms Via Azo Dye Formation with 4’-Chloro-4-Hydroxychalcone. JOTCSA. 2026;(2026-1):1-15. doi:10.18596/jotcsa.1811233

Chicago

Hamed, Muner, Kameran Hussein, and Abdul Majeed Ahmed. 2026. “Spectrophotometric Method for the Determination of Bromhexine-HCl in Bulk and Dosage Forms Via Azo Dye Formation With 4’-Chloro-4-Hydroxychalcone”. Journal of the Turkish Chemical Society Section A: Chemistry, no. 2026-1: 1-15. https://doi.org/10.18596/jotcsa.1811233.

EndNote

Hamed M, Hussein K, Ahmed AM (January 1, 2026) Spectrophotometric Method for the Determination of Bromhexine-HCl in Bulk and Dosage Forms Via Azo Dye Formation with 4’-Chloro-4-Hydroxychalcone. Journal of the Turkish Chemical Society Section A: Chemistry 2026-1 1–15.

IEEE

[1]M. Hamed, K. Hussein, and A. M. Ahmed, “Spectrophotometric Method for the Determination of Bromhexine-HCl in Bulk and Dosage Forms Via Azo Dye Formation with 4’-Chloro-4-Hydroxychalcone”, JOTCSA, no. 2026-1, pp. 1–15, Jan. 2026, doi: 10.18596/jotcsa.1811233.

ISNAD

Hamed, Muner - Hussein, Kameran - Ahmed, Abdul Majeed. “Spectrophotometric Method for the Determination of Bromhexine-HCl in Bulk and Dosage Forms Via Azo Dye Formation With 4’-Chloro-4-Hydroxychalcone”. Journal of the Turkish Chemical Society Section A: Chemistry. 2026-1 (January 1, 2026): 1-15. https://doi.org/10.18596/jotcsa.1811233.

JAMA

1.Hamed M, Hussein K, Ahmed AM. Spectrophotometric Method for the Determination of Bromhexine-HCl in Bulk and Dosage Forms Via Azo Dye Formation with 4’-Chloro-4-Hydroxychalcone. JOTCSA. 2026;:1–15.

MLA

Hamed, Muner, et al. “Spectrophotometric Method for the Determination of Bromhexine-HCl in Bulk and Dosage Forms Via Azo Dye Formation With 4’-Chloro-4-Hydroxychalcone”. Journal of the Turkish Chemical Society Section A: Chemistry, no. 2026-1, Jan. 2026, pp. 1-15, doi:10.18596/jotcsa.1811233.

Vancouver

1.Muner Hamed, Kameran Hussein, Abdul Majeed Ahmed. Spectrophotometric Method for the Determination of Bromhexine-HCl in Bulk and Dosage Forms Via Azo Dye Formation with 4’-Chloro-4-Hydroxychalcone. JOTCSA. 2026 Jan. 1;(2026-1):1-15. doi:10.18596/jotcsa.1811233