Green Alternative in Drug Quality Control Analysis by DoE Optimization: H2 Receptor Antagonists

Nazife Egeşen Halıcı; Cemil Can Eylem; Ayşegül Doğan; Nursabah Elif Başcı Akduman

doi:10.17776/csj.1959298

Green Alternative in Drug Quality Control Analysis by DoE Optimization: H2 Receptor Antagonists

Abstract

H₂ receptor antagonists are often preferred in the treatment of gastroesophageal reflux disease or gastric acidity disorders. In this study, an HPLC method for the simultaneous chromatographic separation of H₂ receptor antagonists, famotidine, nizatidine, ranitidine, and cimetidine active ingredients was developed by implementing green analytical chemistry principles and a chemometric approach. Chromatographic parameters, including ethanol ratio, buffer concentration, flow rate, and column temperature, were optimized using a DoE strategy. This green HPLC method's system compatibility, specificity, sensitivity, linearity, accuracy, precision, recovery, stability, robustness, and consistency parameters were validated only for the analysis of famotidine in the pharmaceutical preparation. The linearity range was 1.5-75 µg/mL, LOD was 0.5 µg/mL, and LOQ was 1.5 µg/mL. Afterward, the method specified in the USP monograph for Famotidine tablets was validated by examining the same parameters. The linearity range of this method was 5.0-500 µg/mL, the LOD was 2.0 µg/mL, and the LOQ was 5.0 µg/mL. Cimetidine was chosen as the internal standard (IS) in both methods, and the performance of the methods with and without IS was compared. Validation results showed that the developed method for the famotidine analysis was sensitive, precise, accurate, specific, robust, and consistent. In addition, validated methods were successfully applied to analyze the famotidine-containing pharmaceutical preparation. No statistically significant difference was found between the results. The developed methods, both with and without IS, exhibited lower LOD and LOQ values than the method specified in the USP monograph, while reducing the potential environmental and health hazards associated with the analytical procedure.

Keywords

Chemometric, Design of Experiments (DoE), Green high-performance liquid chromatography, H2 receptor antagonists, Pharmaceutical analysis

Supporting Institution

The work was supported by grants from Hacettepe University Scientific Research Coordination Unit (Project Number: THD-2020-18956)

Project Number

THD-2020-18956

References

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Details

Primary Language

English

Subjects

Instrumental Methods, Quality Assurance, Chemometrics, Traceability and Metrological Chemistry, Separation Science

Journal Section

Research Article

Authors

Nazife Egeşen Halıcı
0000-0002-9352-5097
Türkiye

Cemil Can Eylem
0000-0002-3353-2869
Türkiye

Ayşegül Doğan ^*
0000-0002-5828-4697
Türkiye

Nursabah Elif Başcı Akduman
0000-0001-5370-2362
Türkiye

Publication Date

October 27, 2026

Submission Date

May 27, 2026

Acceptance Date

September 16, 2026

Published in Issue

Year 2026 Volume: 47 Number: 5

DOI

https://doi.org/10.17776/csj.1959298

IZ

https://izlik.org/JA22FC56NJ

APA

Halıcı, N. E., Eylem, C. C., Doğan, A., & Başcı Akduman, N. E. (2026). Green Alternative in Drug Quality Control Analysis by DoE Optimization: H2 Receptor Antagonists. Cumhuriyet Science Journal, 47(5), 871-883. https://doi.org/10.17776/csj.1959298

AMA

1.Halıcı NE, Eylem CC, Doğan A, Başcı Akduman NE. Green Alternative in Drug Quality Control Analysis by DoE Optimization: H2 Receptor Antagonists. CSJ. 2026;47(5):871-883. doi:10.17776/csj.1959298

Chicago

Halıcı, Nazife Egeşen, Cemil Can Eylem, Ayşegül Doğan, and Nursabah Elif Başcı Akduman. 2026. “Green Alternative in Drug Quality Control Analysis by DoE Optimization: H2 Receptor Antagonists”. Cumhuriyet Science Journal 47 (5): 871-83. https://doi.org/10.17776/csj.1959298.

EndNote

Halıcı NE, Eylem CC, Doğan A, Başcı Akduman NE (October 1, 2026) Green Alternative in Drug Quality Control Analysis by DoE Optimization: H2 Receptor Antagonists. Cumhuriyet Science Journal 47 5 871–883.

IEEE

[1]N. E. Halıcı, C. C. Eylem, A. Doğan, and N. E. Başcı Akduman, “Green Alternative in Drug Quality Control Analysis by DoE Optimization: H2 Receptor Antagonists”, CSJ, vol. 47, no. 5, pp. 871–883, Oct. 2026, doi: 10.17776/csj.1959298.

ISNAD

Halıcı, Nazife Egeşen - Eylem, Cemil Can - Doğan, Ayşegül - Başcı Akduman, Nursabah Elif. “Green Alternative in Drug Quality Control Analysis by DoE Optimization: H2 Receptor Antagonists”. Cumhuriyet Science Journal 47/5 (October 1, 2026): 871-883. https://doi.org/10.17776/csj.1959298.

JAMA

1.Halıcı NE, Eylem CC, Doğan A, Başcı Akduman NE. Green Alternative in Drug Quality Control Analysis by DoE Optimization: H2 Receptor Antagonists. CSJ. 2026;47:871–883.

MLA

Halıcı, Nazife Egeşen, et al. “Green Alternative in Drug Quality Control Analysis by DoE Optimization: H2 Receptor Antagonists”. Cumhuriyet Science Journal, vol. 47, no. 5, Oct. 2026, pp. 871-83, doi:10.17776/csj.1959298.

Vancouver

1.Nazife Egeşen Halıcı, Cemil Can Eylem, Ayşegül Doğan, Nursabah Elif Başcı Akduman. Green Alternative in Drug Quality Control Analysis by DoE Optimization: H2 Receptor Antagonists. CSJ. 2026 Oct. 1;47(5):871-83. doi:10.17776/csj.1959298

As of 2026, Cumhuriyet Science Journal will be published in six issues per year, released in February, April, June, August, October, and December

Green Alternative in Drug Quality Control Analysis by DoE Optimization: H2 Receptor Antagonists

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