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Journals / Journal of the Turkish Chemical Society Section A: Chemistry / 2026 / Volume: 2026 Issue: 2

Synthesis of Bis-Schiff Base Reagents and their Application in the Spectrophotometric Determination of Mesalazine via Azo Dye Formation

Ammar S. Mohammed(University of Kirkuk, College Science)0000-0003-4011-4187
Esraa Majeed(College of Pharmacy, University of Kirkuk, Kirkuk, Iraq)0009-0003-0251-1891
Muner Hamed(University of Kirkuk, Kirkuk, Iraq)0009-0004-9160-1449
Ali Atiyah(University of Kirkuk, College Science)0009-0001-3530-1626
Pages
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Publication Date
2026-10-22
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

These findings support the applicability of the proposed SH1-based spectrophotometric method for routine pharmaceutical quality-control analysis.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Mesalazine (5-aminosalicylic acid) is an important first-line anti-inflammatory drug widely used in the management of inflammatory bowel diseases, particularly ulcerative colitis, making its reliable determination in pharmaceutical formulations important for routine quality control.
📊
Key Findings & Data:In this study, bis-Schiff base reagents were synthesized by condensation of 4,4′-diaminoazobenzene with substituted aromatic aldehydes.
💡
Conclusion & Impact:These findings support the applicability of the proposed SH1-based spectrophotometric method for routine pharmaceutical quality-control analysis.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Mesalazine · spectrophotometry · Bis-Schiff base

Abstract

Mesalazine (5-aminosalicylic acid) is an important first-line anti-inflammatory drug widely used in the management of inflammatory bowel diseases, particularly ulcerative colitis, making its reliable determination in pharmaceutical formulations important for routine quality control. In this study, bis-Schiff base reagents were synthesized by condensation of 4,4′-diaminoazobenzene with substituted aromatic aldehydes. Among the synthesized derivatives, 4,4′-bis[(4-hydroxybenzylidene)amino]azobenzene (SH1) was selected as the chromogenic reagent because it provided a superior analytical response compared with SH2. The novelty of the proposed method lies in the use of laboratory-synthesized SH1 as a coupling reagent for diazotized mesalazine, producing a color-stable azo product in alkaline medium with a maximum absorbance at 530 nm. The analytical procedure is simple and low-volume, employs a predominantly aqueous final reaction medium, and does not require chromatographic separation or solvent-extraction steps, thereby reducing solvent and instrumental requirements. Under optimized conditions, Beer’s law was obeyed over the concentration range of 2.0–20.0 μg/mL, with a molar absorptivity of 7.580 × 10³ L/mol/cm and Sandell’s sensitivity of 0.0202 μg cm⁻². The method showed recoveries of 99.20–100.83%, with RSD values of 0.70–0.80%, and a limit of detection of 0.1540 μg/mL. Good selectivity and robustness were observed, and the method was successfully applied to the determination of mesalazine in Pentasa® tablets. These findings support the applicability of the proposed SH1-based spectrophotometric method for routine pharmaceutical quality-control analysis.

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Cite This Article

Mohammed, A. S., Majeed, E., Hamed, M., Atiyah, A. (2026). Synthesis of Bis-Schiff Base Reagents and their Application in the Spectrophotometric Determination of Mesalazine via Azo Dye Formation. Journal of the Turkish Chemical Society Section A: Chemistry, Volume: 2026 Issue: 2. https://doi.org/10.18596/jotcsa.2000541

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References (68)

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  42. Salih ES, Al-Enizzi M. Spectrophotometric assay of mesalazine in pharmaceutical preparations via oxidative coupling reaction with o-cresol and sodium metaperiodate. J Educ Sci. 2020 Mar 1;29(1):279–92. Available from:.
  43. Ahmed Shehab A, Habboo Muhammed D. Spectrophotometric determination of mesalazine via oxidative coupling reaction. Syst Rev Pharm. 2020;11(6):922–9. Available from:.
  44. Al-Obaidi MSM, Al-Samarrai ET. Spectrophotometric determination of mesalazine by a charge transfer complex. Int J Health Sci (Qassim). 2022 Jun 21;10068–78. Available from:.
  45. Kumar A, Rani P. A quick visible spectrophotometry approach for the assessment of mesalazine in pharmaceutical preparations. Pharm Chem J. 2023 Jan 13;56(10):1411–8. Available from:.
  46. Ghurghure S, Sawant K, Deokar SS. UV spectrophotometric method development and validation of mesalazine in bulk and solid dosage form (Research article). Int J Pharm Biol Sci. 2021 Jan 1;11(1):131–5. Available from:.
  47. Al-Hayale MAA, Yousif NK, Aziz AT, Sultan SH. Spectrophotometric determination of mesalazine in pharmaceutical preparations by diazotization and coupling with 2,6-dihydroxytoluene as a new coupling agent. Rafidain J Sci. 2019 Jun 1;28(2):47–55. Available from:.
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  49. Taha SS, Ali DS. Oxidative coupling assay for mesalazine determination in pharmaceuticals and spiked human plasma utilizing syringic acid. Masunov AE, editor. J Spectrosc. 2023 Jan 5;2023(1):4583013. Available from:.
  50. Al-Ramadhani GL, Al-Mtioti S. Determination of mesalazine spectrophotometry based on the charge transfer complex n- π using reagent p-bromanil. J Educ Sci. 2019 Jun 1;28(2):71–84. Available from:.
  51. Abdelwhab NS, Habib NM, Abdelrahman MM, Mahmoud HM, Emam AA. Determination of sulphasalazine and its related compounds by simple, smart, validated, green spectrophotometric methods. J AOAC Int. 2022 Mar 15;105(2):352–61. Available from:.
  52. Anumolu PD, Gurrala S, Gellaboina A, Mangipudi DG, Menkana S, Chakka R. Spectrophotometric quantification of anti-inflammatory drugs by application of chromogenic reagents. Turkish J Pharm Sci. 2019 Dec 1;16(4):410–5. Available from:.
  53. Saeed RDM, Al-Enizzi MS, Yahya NM. Using benzidine reagent for spectrophotometric determination of mesalazine by oxidative coupling reaction. Chem Probl. 2026;24(3):440–50. Available from:.
  54. Tsamis V, Tsanaktsidou E, Karavasili C, Zacharis CK, Bouropoulos N, Fatouros DG, et al. Development and validation of HPLC-DAD and LC-(ESI)/MS methods for the determination of sulfasalazine, mesalazine and hydrocortisone 21-acetate in tablets and rectal suppositories: In vitro and ex vivo permeability studies. J Chromatogr B. 2022 May;1198:123246. Available from:.
  55. Pastorini E, Locatelli M, Simoni P, Roda G, Roda E, Roda A. Development and validation of a HPLC-ESI-MS/MS method for the determination of 5-aminosalicylic acid and its major metabolite N-acetyl-5-aminosalicylic acid in human plasma. J Chromatogr B. 2008 Sep;872(1–2):99–106. Available from:.
  56. Chaudhari NA, Ranpise NS. Determination of mesalamine in bulk and suppository dosage forms through the development and validation of stability- indicating RP-HPLC method. Curr Pharm Anal. 2024 Jul;20(6):433–43. Available from:.
  57. Alhadad K, Al-Salman H. Chromatographic spectrophotometric determination using reverse-phase HPLC technique for mesalazine or mesalamine. Georgian Med News. 2023 Sep;342:58–65. Available from:.
  58. Teradale AB, Lamani SD, Ganesh PS, Kumara Swamy BE, Das SN. CTAB immobilized carbon paste electrode for the determination of mesalazine: A cyclic voltammetric method. Sens Bio-Sensing Res. 2017 Sep;15:53–9. Available from:.
  59. Štěpánková M, Šelešovská R, Janíková L, Chýlková J. Voltammetric determination of mesalazine in pharmaceutical preparations and biological samples using boron-doped diamond electrode. Chem Pap. 2017 Aug 25;71(8):1419–27. Available from:.
  60. Nouri A, Noroozifar M. Electrochemical determination of mesalazine by modified graphite paste electrode with poly (Benzoquinone) chromium(III) complex. Iran Chem Soc Anal Bioanal Chem Res. 2018;5(2):343–52. Available from:.
  61. Clayden J, Greeves N, Warren S. Organic Chemistry. 2nd Edition. Oxford University Press; 2012. Available from:.
  62. 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. J Turkish Chem Soc Sect A Chem. 2026 Jan 15;(2026–1):1811233. Available from:.
  63. 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. 2024 Dec 3;11(4):1461–72. Available from:.
  64. Atiyah AM, Mohammed AA, Ahmed AMK. Spectrophotometric determination of meloxicam in pure form and its pharmaceutical preparations via oxidative coupling reaction. Bull Pharm Sci Assiut Univ. 2024 Oct 30;47(2):1049–62. Available from:.
  65. Nigović B, Šimunić B. Determination of 5-aminosalicylic acid in pharmaceutical formulation by differential pulse voltammetry. J Pharm Biomed Anal. 2003 Feb;31(1):169–74. Available from:.
  66. Cui FL, Fan J, Li W, Fan YC, Hu ZD. Fluorescence spectroscopy studies on 5-aminosalicylic acid and zinc 5-aminosalylicylate interaction with human serum albumin. J Pharm Biomed Anal. 2004 Jan;34(1):189–97. Available from:.
  67. Ceylan B, Tekkeli EK, Önal C. Development of an HPLC method for the determination of mesalazine in human plasma by fluorimetric derivatization and application to a prototype pharmacokinetic study. J Fluoresc. 2022 Jan 19;32(1):319–25. Available from:.
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