Synthesis of New Azo Compounds and Their Application for a Simple Spectrophotometric Determination of Methyldopa Drug Using Anthranilic Acid and 2-Aminopyrimidine as Reagents

Abstract

The goal of the current work is to synthesize methyldopa derivatives. Based on these reactions, two easy, speedy, accurate, inexpensive, and sensitive spectrophotometric approaches have been established for determining methyldopa (MED) in both pure and pharmaceutical forms. The proposed azo-coupling method depends on forming an azo compound between methyldopa drug and 2-AMPY or ANTH to produce two compounds of MED-2AMPY and MED-ANTH in the alkaline medium. The characterization of synthesized compounds utilizing UV-Visible and FT-IR spectra. FT-IR spectra of 2AMPY-MED confirm the existence of OH, C-Hor, C-Hal, NH, N=N, C=O, and C=C vibration at 3455, 3059, 2973, 3100, 1476,1692, and 1560 cm-1, and FT-IR spectra of ANTH-MED confirm the existence of OH, C-Hor, NH, C=O and N=N vibration at 3490, 3050, 3100, 1701 and 1462 cm-1, correspondingly. The obtained color of azo compounds is spectrophotometrically measured for the previously mentioned azo compounds at 450 and 455 nm, respectively. Under perfect conditions, the azo compound solutions exhibited molar absorptivities of 1563.0058 and 2091.0285 L.mol-1.cm-1, Sandell's sensitivity of 0.135 and 0.10 µg.cm-1, and Beer-Lambert's law are obeyed over the ranges 6.25- 62.5 mg. L-1 for the two developed procedures, respectively.

Keywords

• 2-amino pyrimidine
• anthranilic acid
• spectrophotometry
• methyldopa
• pharmaceutical formulations.

Supporting Institution

Collage of science, University of Diyala, Iraq.

Project Number

2

Thanks

The researchers extend their gratitude to University of Diyala and the College of Science for providing them with the necessary requirements to complete this work.

References

1. 1. Gotardo MA, Lima LS, Sequinel R, Rufino JL, Pezza L, Pezza HR. A simple spectrophotometric method for the determination of methyldopa using p-chloranil in the presence of hydrogen peroxide. Eclética Química. 2008;33:7-12.
2. 2. Al-Abachi MQ, Al-Uzri WA, Abed SS. Batch and Flow-Injection Spectrophotometric Determination of Methyldopa Using Metochlopramide as diazotized Chromogenic Reagent. Iraqi National Journal of Chemistry. 2013;49:12-24.
3. 3. Zečević M, Živanović LJ, Agatonovic-Kustrin S, Minic D. The use of a response surface methodology on HPLC analysis of methyldopa, amiloride and hydrochlorothiazide in Tablets. Journal of pharmaceutical and biomedical analysis. 2001 Mar 1;24(5-6):1019-25.
4. 4. Ting S. Liquid chromatographic determination of methyldopa and methyldopa-thiazide combinations in dosage forms. Journal of the Association of Official Analytical Chemists. 1983 Nov 1;66(6):1436-42.
5. 5. Susan T, Collaborators: Brown RL Dougherty LA Schepman JB Doucette YH Schneider PJ Perry PJ Rihbany LA Gordon K. Liquid chromatographic determination of methyldopa and methyldopa-thiazide combinations in Tablets: collaborative study. Journal of the Association of Official Analytical Chemists. 1984 Nov 1;67(6):1118-20. 6. J. Ballantine and A. D. Woolfson, "Determination of catecholamines in pharmaceutical preparations by differential pulse polarography at the glassy carbon electrode," Int. J. Pharm., vol. 3, no. 4–5, pp. 239–246, 1979.
6. 7. Erdoğdu G, Yağci ŞZ, Savan EK. Investigation of the voltammetric behavior of methyldopa at a poly (p-Aminobenzene Sulfonic Acid) modified sensor. Turkish Journal of Pharmaceutical Sciences. 2019 Dec;16(4):450.
7. 8. Berzas Nevado JJ, Lemus Gallego JM, Buitrago Laguna P. Spectrophotometric determination of dopamine and methyldopa with metaperiodate by flow injection analysis. Fresenius' journal of analytical chemistry. 1995 Jan;353(2):221-3.
8. 9. Ribeiro PR, Neto JG, Pezza L, Pezza HR. Flow-injection spectrophotometric determination of methyldopa in pharmaceutical formulations. Talanta. 2005 Jul 15;67(1):240-4.

9. 10. Matthieu T, Junior AR, Vila M. A Simple Flow Injection Spectrophotometric Method for the Determination of α-Methyldopa in Pharmaceutical Preparations Original Paper. Journal of Flow Injection Analysis. 2004;21(2):132.
10. 11. Pathak VN, Shukla SR, Shukla IC. Direct titrimetric determination of the antihypertensive drugs methyldopa and propranolol in pharmaceutical preparations. Analyst. 1982;107(1278):1086-7. 12. Badawy SS, Issa YM, Tag‐Eldin AS. Potentiometric determination of l‐dopa, carbidopa, methyldopa and aspartame using a new trinitrobenzenesulfonate selective electrode. Electroanalysis. 1996 Nov;8(11):1060-4.
11. 13. Sanati AL, Faridbod F. Electrochemical determination of methyldopa by graphene quantum dot/1-butyl-3-methylimidazolium hexafluoro phosphate nanocomposite electrode. Int. J. Electrochem. Sci. 2017 Sep 1;12(9):7997-8005.
12. 14. Rashid QN, Bakir MH, Baban SO. Spectrophotometric determination of methyldopa in pure form and in the pharmaceutical preparations. Tikrit Journal of Pharmaceutical Sciences. 2016;11(1):67-77.
13. 15. Upadhyay K, Asthana A, Tamrakar RK. Extractive spectrophotometric determination of α-methyldopa in bulk dosage and in its formulations. Research on Chemical Intermediates. 2015 Aug;41(8):5521-8.
14. 16. Bahgat EA. Spectrophotometric Microdetermination of Methyldopa and Etilefrine Hydrochloride using Copper (II)-Neocuproine Reagent in Pure Form and Pharmaceutical Formulations. Scholars Research Library. 2018.
15. 17. Sultan MA. New, simple and validated kinetics spectrophotometric method for determination of moxifloxacine in its pharmaceutical formulations. Arabian Journal of Chemistry. 2009 Oct 1;2(2):79-85.
16. 18. Fiaz T, Fatima N, Zaidi SZ, Abbas T, Kazimi MR. Investigation of iron complex formation of anti-hypertensive drug: Methyldopa. American Journal of Analytical Chemistry. 2015 May 5;6(06):551.
17. 19. Helaleh MI, Rahman N, Abu-Nameh ES. Use of cerium (IV) nitrate in the spectrophotometric determination of levodopa and methyldopa in the pure form and pharmaceutical preparations. Analytical sciences. 1997 Dec 10;13(6):1007-10.
18. 20. Abdullah AM, Hasson MM, Thani MZ. Synthesis, thermal analysis, spectroscopy and magnetic properties of some transition metals complexes derived from new azo compound. Materials Today: Proceedings. 2020 Jan 1;20:595-8.
19. 21. Thani MZ, Dadoosh SA, Abdullah AM, Fahad AS, Fahad YS, Faraj FL. Evaluation of salbutamol in pure form and pharmaceutical formulations using spectrophotometry and green nonionic surfactant of cloud point extraction. InJournal of Physics: Conference Series 2021 Mar 1 (Vol. 1853, No. 1, p. 012022). IOP Publishing.
20. 22. Dadoosh SA, Thani MZ, Abdullah AM, Fahad AS, Fahad YS. Development of an Ecological-friendly Method for Dexamethasone Determination and Cloud Point Extraction in pharmaceutical formulations using Schiff Base Reaction. Egyptian Journal of Chemistry. 2021 Sep 1;64(9):5083-92. 23. P. R. S. Ribeiro, J. A. G. Neto, L. Pezza, and H. R. Pezza, "Flow-injection spectrophotometric determination of methyldopa in pharmaceutical formulations," Talanta, vol. 67, no. 1, pp. 240–244, 2005.
21. 24. S. Ashour, "A novel sensitive colorimetric determination of catecholamine drug in dosage form via oxidative coupling reaction with MBTH and potassium ferricyanide," Drug Anal. Res., vol. 5, no. 1, pp. 51–58, 2021.
22. 25. T. Fiaz, N. Fatima, S. Z. A. Zaidi, T. Abbas, and M. R. Kazimi, "Investigation of Iron Complex Formation of Anti-Hypertensive Drug: Methyldopa," Am. J. Anal. Chem., vol. 6, no. 06, p. 551, 2015.
23. 26. S. Emara, T. Masujima, W. Zarad, M. Kamal, M. Fouad, and R. El-Bagary, "A Combination of isocratic and gradient elution modes in HPLC with the aid of time-overlapping process for rapid determination of methyldopa in human urine," J. Liq. Chromatogr. Relat. Technol., vol. 38, no. 2, pp. 153–162, 2015.
24. 27. M. Z. Thani, S. A. Dadoosh, A. S. Fahad, A. M. Abdullah, and Y. S. Fahad, "Synthesis of New Azo Compound and its Application for Spectrophotometric Determination of Sulfamethoxazole and Extraction using Cloud Point Extraction" IJDDT, Volume 12 Issue 3, July - September 2022.
25. 28. D. L. Pavia, G. M. Lampman, G. S. Kriz, and J. A. Vyvyan, Introduction to spectroscopy. Cengage learning, 2014.
26. 29. Santos LD, Santos QO, Moreno I, Novaes CG, dos Santos MJ, Bezerra MA. Multivariate optimization of a simultaneous cloud point extraction procedure of Cd, Cu and Ni from sediments samples and determination by ICP OES. Journal of the Brazilian Chemical Society. 2016;27:745-52.
27. 30. Emara S, Masujima T, Zarad W, Kamal M, Fouad M, El-Bagary R. An eco-friendly direct injection HPLC method for methyldopa determination in serum by mixed-mode chromatography using a single protein-coated column. Journal of chromatographic science. 2015 Sep 1;53(8):1353-60.
28. 31. BICHAN MJ, ABDOON FM. A NOVEL SPECTROPHOTOMETRIC DETERMINATION OF METHYLDOPA THROUGH TERNARY COMPLEXATION PROCEDURE USING FE (III), MN (II), AND CO (II) WITH 2-AMINOPYRIDINE. Asian Journal of pharmaceutical and Clinical Research. 2019;12(3):366-71.
29. 32. Mohammadi SZ, Beitollahi H, Jasemi M, Akbari A. Nanomolar determination of methyldopa in the presence of large amounts of hydrochlorothiazide using a carbon paste electrode modified with graphene oxide nanosheets and 3‐(4′‐amino‐3′‐hydroxy‐biphenyl‐4‐yl)‐acrylic acid. Electroanalysis. 2015 Oct;27(10):2421-30.
30. 33. Al-Abachi MQ, Sinan R, Haddi H. Spectrophotometric determination of methyldopa and dopamine hydrochloride in pharmaceutical preparations using flow injection analysis. National Journal of Chemistry. 2009;36:597-604.
31. 34. AL-Da'amy MA, AL-Moswi RF. Asensitive colorimetric method for the determination of Methyldopa in pharmaceutical preparation via oxidative coupling organic reaction with Thiamine Hydrochloride in the presence of potassium periodate. kerbala journal of pharmaceutical sciences. 2013(6).
32. 35. Garcia LF, Cunha CE, Moreno EK, Thomaz DV, Sanz Lobón G, Luque R, Somerset V, de Souza Gil E. Nanostructured TiO2 carbon paste based sensor for determination of methyldopa. Pharmaceuticals. 2018 Oct 5;11(4):99.
33. 36. Sanati AL, Faridbod F. Electrochemical determination of methyldopa by graphene quantum dot/1-butyl-3-methylimidazolium hexafluoro phosphate nanocomposite electrode. Int. J. Electrochem. Sci. 2017 Sep 1;12(9):7997-8005.
34. 37. Antunes RS, Thomaz DV, Garcia LF, de Souza Gil E, Sommerset VS, Lopes FM. Determination of methyldopa and paracetamol in pharmaceutical samples by a low cost genipa americana l. polyphenol oxidase based biosensor. Advanced Pharmaceutical Bulletin. 2019 Aug;9(3):416.
35. 38. Bahrami G, Kiani A, Mirzaeei S. A rapid high performance liquid chromatographic determination of methyldopa in human serum with fluorescence detection and alumina extraction: Application to a bioequivalence study. Journal of Chromatography B. 2006 Mar 7;832(2):197-201.