Determination of isohydrafural and methyluracil in ear drops by high performance liquid chromatography

Uncu, Livia

doi:10.2478/amma-2023-0049

Abstract

Objective

The aim of current study was the development and validation of a reversed-phase high-pressure liquid chromatography (RPHPLC) method for the quantitative determination of two active ingredients, isohydrafural (IHF) and methyluracil (MU) in fixed dose combination ear drops.

Methods:

An efficient separation of the two compounds was achieved on a Teknokroma C1 5μm (150*4,6mm) column, with a methanol: water 60:40 (V: V) mobile phase, at 300C temperature and 0.6 mL/min flow-rate. The total analysis time was 5.5 min.

Result:

The verified validation parameters were: linearity, selectivity, specificity, precision (repeatability and reproducibility), robustness, limit of detection and quantification.

Conclusions:

Good separation and lack of interference from other chromatographic peaks, rapidanalysis times were obtained. The newly developed chromatographic method can be applied for the analysis of fixed dose combination ear drops with isohydrafural and methyluracil.

References

DeAntonio R, Yarzabal JP, Cruz JP, Schmidt JE, Kleijnen J. Epidemiology of otitis media in children from developing countries: a systematic review. Int J Pediatr Otorhinolaryngol. 2016; 85:65–74. doi: 10.1016/j. ijporl.2016.03.032
Search in Google Scholar Back to article
Alizadeh M, Jalal M, Hamed K, et al. Recent Updates on Anti-Inflammatory and Antimicrobial Effects of Furan Natural Derivatives. J Inflamm Res. 2020 A; 13:451-463. doi: 10.2147/JIR.S262132
Search in Google Scholar Back to article
Le VVH, Rakonjac J. Nitrofurans: Revival of an „old” drug class in the fight against antibiotic resistance. PLoS Pathog. 2021; 17(7):e1009663. doi: 10.1371/journal.ppat.1009663.
Search in Google Scholar Back to article
Dighe NS. et al. Synthetic and pharmacological profile of furan. Asian Journal of Biosciences 2014; 1(1), 7-14. ISSN 1996-3351.
Search in Google Scholar Back to article
Kumar V. Antimicrobial potential of hydrazone scaffold. International Journal of Academic Research and Development 2018; 3(2), 9-12. ISSN 2455-4197.
Search in Google Scholar Back to article
Rusu A, Moga I-M, Uncu L, Hancu G. The Role of Five-Membered Heterocycles in the Molecular Structure of Antibacterial Drugs Used in Therapy. Pharmaceutics 2023; 15, 2554. doi:10.3390/ pharmaceutics15112554
Search in Google Scholar Back to article
Sadlowski C, Park B, Araujo C, et al. Nitro Sulfonyl Fluorides are a new pharmacophore for the development of antibiotics. Mol Syst Des Eng. 2018; 3(4):599–603. doi: 10.1039/C8ME00011E
Search in Google Scholar Back to article
Stevens M, Howe C, Ray AM, et al. Analogs of nitrofuran antibiotics are potent GroEL/ES inhibitor pro-drugs. Bioorg Med Chem. 2020; 28(22):115710. doi: 10.1016/j.bmc.2020.115710
Search in Google Scholar Back to article
Lyu J, Wang S, Balius TE, et al. Ultra-large library docking for discovering new chemotypes. Nature. 2019; 566(7743):224–9. doi: 10.1038/ s41586-019-0917-9
Search in Google Scholar Back to article
Prisacari V. et al. New antibacterial and antifungal substances from local raw material. Akademos 2010; 17(2), 66-75. ISSN 1857-0461.
Search in Google Scholar Back to article
Stoica AE, Chircov C, Grumezescu AM. Nanomaterials for wound dressings: an up-to-date overview. Molecules 2020; 25:2699. doi: 10.3390/molecules25112699.
Search in Google Scholar Back to article
Kun Harismah, Ramona Khadivi, Ebrahim Balali, et al. Hydrogen-Bonded Dimers of 2-Thiouracil: Insights from Computational Analyses. Biointerface Research in Applied Chemistry 2023; 13 (6), 552. Doi:10.33263/BRIAC136.552
Search in Google Scholar Back to article
Plecheva D, Alekhin E. Oxymethyluracil stimulates reparative regeneration of skin in rats. Eksp. Klin, Farmakol. 2004, 5(67), 63-66. ISSN: 0869-2092
Search in Google Scholar Back to article
Donici E. Development, analysis and standardization of combined pharmaceutical forms containing Isohydrafural. Doctoral Thesis in Pharmaceutical Sciences 2020. 279 p.
Search in Google Scholar Back to article
Leonidov NB, Kolesnikova MA, Seleznev NG, Cherkunov BF, Tarapina TV. A new pyrimidine-series preparation in the treatment of experimental chemical eye burns. Oftalmol Zh. 1990; (6):344-7.
Search in Google Scholar Back to article
Grabovskiy S, Kabal’nova N, Andriayshina N, et al. In vitro proliferative activity of 6-substituted uracil derivatives. Journal of Pharmacy & Pharmacognosy Research 2021; 9, 357-365. doi:10.56499/ jppres20.944_9.3.357.
Search in Google Scholar Back to article
Uncu L, et al. Compatibility study of isohydrafural and methyluracil in the same pharmaceutical form. Scientific Annals of USMF „Nicolae Testemiţanu” 2010; 423-427. ISSN 1857-1719.
Search in Google Scholar Back to article
Spînu C, Lupu R, Podgornîi A, Nicolai E. Evaluation of methods for determining the ototoxicity of drug substances. Book of abstracts of The 7th International Medical Congress for Students and Young Doctors, May 3-5, 2018; 276-277.
Search in Google Scholar Back to article
Romanova EV, Samoukova TS, Sanaeva EP, Saushkina AS, Fomicheva VI. Development of methods for analyzing an ointment containing anesthesin, methyluracil, furatsilin [Electronic resource] // Ogarev-online. 2020; 1. Access mode: https://journal.mrsu.ru/arts/razrabotkasposobov-analiza-mazi-soderzhashhej-anestezin-metiluracil-furacilin . Accessed 22 Sept 2023.
Search in Google Scholar Back to article
Melnikov AM, Bocharnikova KS. Quantitative determination of methyluracil in soft dosage form with silver nanoparticles by spectrophotometric method. Current issues of science and practice, Collection of scientific articles based on the materials of the VIII International Scientific and Practical Conference. Ufa, 2022; 175-179. eLIBRARY ID: 48547427, available: https://www.elibrary.ru/item.asp?id=48547427, accesat 09/20/2023. Accessed 21 Sept 2023.
Search in Google Scholar Back to article
Uncu A. Development and validation of the high-pressure liquid chromatographic method for the quantitative determination of propylthiohinothiadiazole. Moldovan Medical Journal. 2020;63(3), 32-37. doi:10.5281/zenodo.3958549
Search in Google Scholar Back to article
Nicolai E, Vislouh O, Valica V, Parii S, Uncu L. Stability studies of combined ear drops for the treatment of otitis. Moldovan Medical Journal 2020,63(3), 43-50. doi: 10.5281/zenodo.3958557
Search in Google Scholar Back to article
ICH Harmonised tripartite guideline Q2(R1). Validation of Analytical Procedure: Methodology. International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use. 2005; Available from: https://database.ich.org/sites/default/files/Q2_R1__Guideline.pdf . Accessed 22 Sept 2023.
Search in Google Scholar Back to article
Forootan A, RSj¨oback, JBj¨orkman, B.j¨ogreen, LLinz,and M Kubista. Methods to determine limit of detection and limit of quantification in quantitative real-time PCR (qPCR). Biomolecular Detection and Quantification 2017; 3, 1–6. doi: 10.1016/j.bdq.2017.04.001.
Search in Google Scholar Back to article