Improvement of Tests for the Control of Impurities in Antimicrobial Medicinal Products by Chromatographic Methods: Ciprofloxacin Case Study

The need to reduce analysis time when controlling impurities in medicinal products remains an urgent challenge.

The aim of the study was to use the example of ciprofloxacin in order to select chromatographic conditions that will significantly accelerate and simplify determination of impurities in medicinal products.

Methods: the study was performed using the Chromolith^® Performance RP-18e 100×4.6 mm and Acquity UPLC BEH C18 1.7 μm, 100×2.1 mm columns and the Agilent 1290 Infinity chromatography system with a diode array detector.

Results: the authors of the study worked out gradient elution modes for determination of ciprofloxacin impurities that involved 15 min run time for fast high-performance liquid chromatography and 12 min run time for ultra-performance liquid chromatography. The identification of impurities was performed based on relative retention times of impurity peaks and their comparison with the reference standard chromatogram.

Conclusions: the study demonstrated the possibility of replacing the thin-layer chromatography method used for determination of fluoroquinolonic acid (ciprofloxacin impurity A) with high-performance liquid chromatography. The proposed test conditions allow for identification of ciprofloxacin impurities specified in well-established pharmacopoeias and manufacturers’ product specification files. The obtained data may be used for further development of rapid methods of ciprofloxacin impurities determination in medicinal products. 

1. Георгиевский ВП, ред. Аналитическая химия в создании, стандартизации и контроле качества лекарственных средств. Т. 2. Харьков: НТМТ; 2011. [Georgievsky VP, ed. Analytical Chemistry in the Creation, Standardization and Quality Control of Medicines. V. 2. Kharkov: NTMT; 2011 (In Russ.)]

2. Осипов АС, Попова ОА, Милкина СЕ, Грецкая ТН, Сулименкова АИ. Применение хроматографической колонки с амидным сорбентом для анализа парабенов. Ведомости Научного центра экспертизы средств медицинского применения. 2018;8(1):56–60. [Osipov AS, Popova OA, Milkina SЕ, Gretskaya TN, Sulimenkova AI. The use of a chromatographic column packed with amide sorbent for the analysis of parabens. Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo primeneniya=The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. 2018;8(1):56–60 (In Russ.)] https://doi.org/10.30895/1991-2919-2018-8-1-56-60

3. Исупова НЮ. Быстрая хроматография от сокращения времени анализа к новым областям применения. Фармацевтические технологии и упаковка. 2013;(3):70–2. [Isupova NYu. Fast chromatography from reducing analysis times to new applications. Farmatsevticheskiye tekhnologii i upakovka=Pharmaceutical Technology and Packaging. 2013;(3):70–2 (In Russ.)]

4. Яшин ЯИ, Яшин АЯ. Современные тенденции в хроматографических методах и приборостроении. В кн.: Материалы Всероссийской конференции «Аналитическая хроматография и капиллярный электрофорез». Краснодар; 2013. [Yashin YaI, Yashin AYa. Current trends in chromatographic methods and instrumentation. In: Materials of the All-Russian Conference «Analytical Chromatography and Capillary Electrophoresis». Krasnodar; 2013 (In Russ.)]

5. Pena A, Chmielova D, Lino CM, Solich P. Determination of fluoroquinolone antibiotics in surface waters from Mondego River by high performance liquid chromatography using a monolithic column. J Sep Sci. 2007;30(17):2924–8. https://doi.org/10.1002/jssc.200700363

6. Hubicka U, Zmudzki P, Zuromska-Witek B, Zajdel P, Krzek J. Determination and characterization of selected fluorquinolones oxidation products under potassium permanganate treatment. Acta Poloniae Pharmaceutica – Drug Research. 2015;72(6):1101–14.

7. Pous-Torres S, Torres-Lapasio JR, Garcia-Alvarez-Coque MC. Comparison of the performance of Chromolith® Performance RP-18e, 1.8-mm Zorbax Eclipse XDB-C18 and XTerra MSC18, based on modelling approaches. Anal Bioanal Chem. 2013;405(7):2219–31. https://doi.org/10.1007/s00216-012-6448-y