Development and Validation of a Stability-Indicating HPLC Method for the Simultaneous Determination of Sodium Alginate and Parabens in Pharmaceutical Oral Suspensions
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Abstract
A stability-indicating high-performance liquid chromatographic (HPLC) method was developed and validated for simultaneous quantification of sodium alginate (Na Alg), sodium methylparaben (Na-MP), and sodium propylparaben (Na-PP) in oral suspension formulations. This method addresses the need for reliable quality control of complex pharmaceutical matrices. Separation was achieved on an Ultisil XB-CN(Cyanopropyl) column at 40 °C, using an isocratic mobile phase composed of 0.05 M potassium dihydrogen phosphate buffer (pH 5.2) and acetonitrile (80:20, v/v) at a flow rate of 1.5 mL/min, with detection at 210 nm. The method was validated in accordance with the ICH Q2(R1) and USP guidelines to assess linearity, accuracy, precision, specificity, and robustness. The technique demonstrated excellent linearity (R2 > 0.9998) over the concentration ranges of 10–1500, 1–150, and 0.16–24 μg/mL for Na-Alg, Na-MP, and Na-PP, respectively. The validation results showed high accuracy expressed as recovery (98.65–101.88%) across the tested concentration range of 50% to 150%, precision (%RSD < 1.9%), and sensitivity (LODs: 5.30, 0.038, and 0.062 μg/mL; LOQs: 17.65, 0.127, and 0.207 μg/mL) for Na-Alg, Na MP, and Na-PP, respectively. The degradation products were successfully resolved from the analytes, thereby confirming the specificity of the method. The developed HPLC method used to analyze 34 commercial alginate suspension samples was highly precise (%RSD < 1.5%) and accurate (94.66%–105.20% recovery). It reliably quantified Na-Alg and preservatives (Na-MP and Na-PP), with results consistently matching the label claims. This robust method is suitable for routine quality control and stability testing, and effectively combines regulatory compliance with practical pharmaceutical analysis.
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References
United States Pharmacopeia. (2024). United States Pharmacopeia National Formulary: Monograph for sodium alginate, https://doi.org/10.31003/USPNF_M75750_06_01
Jadach, B., Świetlik, W., & Froelich, A. (2022). Sodium alginate as a pharmaceutical excipient: Novel applications of a well-known polymer. Journal of Pharmaceutical Sciences, 111(5), 1250-1261. https://doi.org/10.1016/j.xphs.2021.12.024.
Akbar, M., Yaqoob, A., Ahmad, A., & Luque, R. (2023). Sodium alginate: An overview. Sodium Alginate-Based Nanomaterials for Wastewater Treatment, 1-17.
Rowe, R. C., Sheskey, P. J., & Quinn, M. E. (Eds.). (2009). Handbook of pharmaceutical excipients (6th ed.). Pharmaceutical Press, (p. 622)
Sanchez-Ballester, N. M., Bataille, B., & Soulairol, I. (2021). Sodium alginate and alginic acid as pharmaceutical excipients for tablet formulation: Structure-function relationship. Carbohydrate Polymers, 270, 118399. https://doi.org/10.1016/j.carbpol.2021.118399.
Teaima, M. A. H. M. O. U. D., Abdelmonem, R. E. H. A. B., Saady, M. A. R. W. A., El-Nabarawi, M. O. H. A. M. E. D., & Shoman, N. A. (2022). Comprehensive overview on recent updates of gastroretentive raft-forming systems. International Journal of Applied Pharmaceutics, 14(3), 40-48. https://doi.org/10.22159/ijap.2022v14i3.44098
Bojorges, H., López-Rubio, A., Martínez-Abad, A., & Fabra, M. J. (2023). Overview of alginate extraction processes: Impact on alginate molecular structure and techno-functional properties. Trends in Food Science & Technology, 140, 104142. https://doi.org/10.1016/j.tifs.2023.104142.
Hefft, D. I., & Adeutnji, C. O. (2024). Alginate in food and beverage formulations. In Applications of Seaweeds in Food and Nutrition (pp. 115-128). Elsevier. https://doi.org/10.1016/B978-0-323-91803-9.00017-2.
Rahman, M. M., Shahid, M. A., Hossain, M. T., Sheikh, M. S., Rahman, M. S., Uddin, N.,& Hossain, I. (2024). Sources, extractions, and applications of alginate: a review. Discover Applied Sciences, 6(8), 443. https://doi.org/10.1007/s42452-024-06151-2
Knarr, M. (2025). Advanced analysis of alginate for treatment of gastroesophageal reflux disease. Gastroenterol Hepatol Open Access, 16(1), 46-49. DOI: 10.15406/ghoa.2025.16.00606
International Council for Harmonisation. Validation of analytical procedures: Text and methodology Q2(R1). 2005. https://database.ich.org/sites/default/files/Q2_R1__Guideline.pdf
Donati, I., & Christensen, B. E. (2023). Alginate-metal cation interactions: Macromolecular approach. Carbohydrate polymers, 321, 121280. https://doi.org/10.1016/j.carbpol.2023.121280
Kumar, R. S., & Yagnesh, T. N. S. (2016). Pharmaceutical suspensions: patient compliance oral dosage forms. World Journal of Pharmacy and Pharmaceutical Sciences, 7(12), 1471-1537. DOI: 10.20959/wjpps201612-8159
U.S. Food and Drug Administration. (2019). Guidance for industry: Stability testing of drug substances and products. https://www.fda.gov/regulatory-information/search-fda-guidance-documents
Donati, I., & Christensen, B. E. (2023). Alginate-metal cation interactions: Macromolecular approach. Carbohydrate polymers, 321, 121280. https://doi.org/10.1016/j.carbpol.2023.121280
Sengupta, P., Chatterjee, B., & Tekade, R. K. (2018). Current regulatory requirements and practical approaches for stability analysis of pharmaceutical products: A comprehensive review. International journal of pharmaceutics, 543(1-2), 328-344. https://doi.org/10.1016/j.ijpharm.2018.04.007
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). (2003). Q1A(R2): Stability testing of new drug substances and products. https://www.ich.org/page/quality-guidelines.
United States Pharmacopeia. (2024). United States Pharmacopeia, General Chapter <311> Alginates Assay, USP-NF: https://doi.org/10.31003/USPNF_M99070_01_01
Yang, H. J., Seo, E., Yun, C. I., & Kim, Y. J. (2021). Determination of sodium alginate in processed food products distributed in Korea. Journal of Food Hygiene and Safety, 36(6), 474-480. https://doi.org/10.31003/USPNF_M99070_01_01
Hanif, M., Shah, S., Rasool, N., Abbas, G., Saadullah, M., Khan, S. M., & Iqbal, O. (2021). Sodium alginate and pectin estimation in raft forming pharmaceuticals by high performance liquid chromatography method. Acta Chromatographic, 33(2), 127-133. DOIhttps://doi.org/10.13103/jfhs.2021.36.6.474
Vijayaraj, S., Palei, N. N., Archana, D., Lathasri, K., & Rajavel, P. (2020). Quality by design (Qbd) approach to develop stability indicating HPLC method for estimation of rutin in chitosan-sodium alginate nanoparticles. Brazilian Journal of Pharmaceutical Sciences, 56, e18793. https://doi.org/10.1556/1326.2020.00765
Mohammed, A., Bissoon, R., Bajnath, E., Mohammed, K., Lee, T., Bissram, M., & Ward, K. (2018). Multistage extraction and purification of waste Sargassum natans to produce sodium alginate: An optimization approach. Carbohydrate polymers, 198, 109-118. https://doi.org/10.1590/s2175-97902020000318793
Devina, N., Eriwati, Y. K., & Santosa, A. S. (2018, August). The purity and viscosity of sodium alginate extracted from Sargassum brown seaweed species as a basic ingredient in dental alginate impression material. In Journal of Physics: Conference Series (Vol. 1073, No. 5, p. 052012). IOP Publishing. doi :10.1088/1742-6596/1073/5/052012
Dettmar, P. W., Gil-Gonzalez, D., Fisher, J., Flint, L., Rainforth, D., Moreno-Herrera, A., & Potts, M. (2018). A comparative study on the raft chemical properties of various alginate antacid raft-forming products. Drug Development and Industrial Pharmacy, 44(1), 30-39. https://doi.org/10.1080/03639045.2017.1371737
Ravanal, M. C., Sharma, S., Gimpel, J., Reveco-Urzua, F. E., Øverland, M., Horn, S. J., & Lienqueo, M. E. (2017). The role of alginate lyases in the enzymatic saccharification of brown macroalgae, Macrocystis pyrifera and Saccharina latissima. Algal research, 26, 287-293. https://doi.org/10.1016/j.algal.2017.08.012
Kim, T. H., Choi, W. I., Kim, Y. S., & Oh, K. K. (2015). A novel alginate quantification method using high-performance liquid chromatography (HPLC) for pretreatment of Saccharina japonica. Journal of applied phycology, 27, 511-518. DOI: 10.1007/s10811-014-0298-2
Awad, H., & Aboul-Enein, H. Y. (2013). A validated HPLC assay method for the determination of sodium alginate in pharmaceutical formulations. Journal of Chromatographic Science, 51(3), 208-214. https://doi.org/10.1093/chromsci/bms129
Rele, R. V., & Warkar, C. B. (2010). Reversed phase high pressure liquid chromatographic technique for determination of sodium alginate from oral suspension. Int. J. Pharm. Tech. Res, 2, 1634-1638. ISSN : 0974-4304
British Pharmacopoeia. (2024). Alginate raft-forming oral suspension. In BP 2024 (Ph. Eur. 11.3 update). Effective from April 1, 2024. https://www.pharmacopoeia.com/bp-2024/formulated-specific/alginate-raft-forming-oral-suspension.date=2024-04-01.
Uriel, M., Marro, D., & Gómez Rincón, C. (2023). An adequate pharmaceutical quality system for personalized preparation. Pharmaceutics, 15(3), 800. https://doi.org/10.3390/pharmaceutics15030800.
World Health Organization. (2008). WHO Expert Committee on Specifications for Pharmaceutical Preparations: Forty-second report (Vol. 948). World Health Organization.
Botet, J. (2015). Good quality practice (GQP) in pharmaceutical manufacturing: A handbook. Bentham Science Publishers. https://doi.org/10.2174/97816810811441150101
Dinç-Zor, Ş., Aşçi, B., Dönmez, Ö. A., & Hacimustafa, Ö. (2019). Experimental design approach to optimize HPLC separation of active ingredients, preservatives, and colorants in syrup formulation. Journal of AOAC International, 102(5), 1523–1529. https://doi.org/10.1093/jaoac/102.5.1523.
Snyder, L. R., Kirkland, J. J., & Glajch, J. L. (2012). Practical HPLC method development (2nd ed.). John Wiley & Sons. https://doi.org/10.1002/9781118592014
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (2023). Analytical procedure development Q14. https://www.ich.org/page/quality-guidelines
Patwekar, S. L., Sakhare, R. S., & Nalbalwar, N. N. (2015). HPLC method development and validation: A general concept. International Journal of Chemical and Pharmaceutical Sciences, 6(1), 1-14. doi :10.1088/1742-6596/1073/5/052012
United States Pharmacopeia Convention. (2024). General chapter: <1225> validation of compendial procedures method. In USP47-NF42. Currently official on January 5, 2024.
United States Pharmacopeia Convention. (2024). General chapter <621> chromatography. In USP47-NF42.
Murshed, F. A., Alnedhary, A. A., Almaqtari, M. A., Al Huzaim, A. A. S., Al-kufl, D., & Abu Al-rejal, A. A. (2025). Method validation and assessment of total antioxidants, polyphenols, flavonoids, and vitamin C in cultivated mulberry in Yemen. Sana’a University Journal of Applied Sciences and Technology, 3(2), 730–739. https://doi.org/10.59628/jast.v3i2.1546
Murshed, F. A., Alnedhary, A. A., Almaqtari, M. A., & Al-herdy, F. A. (2025). Method validation and determination of total antioxidants, polyphenols, flavonoids, and vitamin C contents in the Yemeni grapes. Sana’a University Journal of Applied Sciences and Technology, 3(2), 740–748. https://doi.org/10.59628/jast.v3i2.1499
Murshed, F., Alnedhary, A. A., Al-Hamadi, M. M., & Al-kufl, D. (2024). Development and optimization of the sample preparation method to determine the antioxidants in the Yemeni almond. Sana’a University Journal of Applied Sciences and Technology, 2(3), 254–264. https://doi.org/10.59628/jast.v2i3.934
Al-Hammadi, M. M., Numan, A. A., Alnedhary, A. A., Murshed, F. A., & Al-Hoded, T. H. (2023). Optimization, validation, and application of a quantitative GC/NPD method for acrylamide determination in Yemeni fried fish samples. Sana’a University Journal of Applied Sciences and Technology, 1(4). https://doi.org/10.59628/jast.v1i4.698
Alnedhary, A. A., Numan, A. A., Al-Hammadi, M. M., Murshed, F. A., & Dubais, H. M. (2021). A comparative study to assess the quality of different marketed brands of metformin HCl. PSM Biological Research, 6(3), 84–95. https://psmjournals.org/index.php/biolres/article