HPLC method for simultaneous quantification of lumacaftor and ivacaftor bulk and pharmaceutical formulations

Year 2023, Volume: 2 Issue: 3, 109 - 117, 29.12.2023

Saniye Özcan Abeer Elriş Serkan Levent

https://doi.org/10.55971/EJLS.1367996

Abstract

In 2015, the Food and Drug Administration granted approval for the use of lumacaftor 200 mg and ivacaftor 125 mg in the treatment of cystic fibrosis patients who possess the F508del mutation, namely those who are 12 years of age or older. Since its approval, the medicine has been implemented in clinical settings, although the presence of numerous disputes, with the aim of mitigating disease symptoms and enhancing the overall quality of life. Given the existing gaps in the literature regarding the analysis of the amalgamation of these two active substances, a straightforward and practical HPLC approach has been devised in adherence to the guidelines outlined in the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2(R1) document. To accomplish this objective, the process of separation was successfully carried out using a monolithic silica stationary phase (Chromolith High Resolution RP-18e, 100 mm × 4.6 mm i.d., Merck KGaA, Darmstadt, Germany). The separation process was conducted using a gradient mode. The initial composition of the mobile phase consisted of acetonitrile and a phosphate buffer solution with a concentration of 0.030 M and a pH of 3.5. The flow rate was recorded as 1.0 mL/min, and avanafil was used as an internal standard. The improved and verified approach has demonstrated successful application in bulk and pharmaceutical formulation evaluations when utilizing the ivacaftor/lumacaftor combination.

Keywords

Bulk form, HPLC, Ivacaftor, Lumacaftor, Pharmaceutical form

Ethical Statement

No ethical statement.

Supporting Institution

Anadolu University Scientific Research Projects funded.

Thanks

This research was funded by Anadolu University Scientific Research Projects Fund Commission grant number 2005S039 and project student Berke UZUNOĞLU for valuable contributions.

References

• Ni Q, Chen X, Zhang P, Yang L, Lu Y, Xiao F, et al. Systematic estimation of cystic fibrosis prevalence in Chinese and genetic spectrum comparison to Caucasians. Orphanet Journal of Rare Diseases. 2022;17(1):129. https://doi.org/10.1186/s13023-022-02279-9
• Sontag MK, Hammond KB, Zielenski J, Wagener JS, Accurso FJ. Two-tiered immunoreactive trypsinogen-based newborn screening for cystic fibrosis in Colorado: screening efficacy and diagnostic outcomes. The Journal of pediatrics. 2005;147(3):S83-S8. https://doi.org/10.1016/j.jpeds.2005.08.005
• Graeber SY, Mall MA. The future of cystic fibrosis treatment: from disease mechanisms to novel therapeutic approaches. The Lancet. 2023. https://doi.org/10.1016/S0140-6736(23)01608-2
• Keogh RH, Szczesniak R, Taylor-Robinson D, Bilton D. Up-to-date and projected estimates of survival for people with cystic fibrosis using baseline characteristics: A longitudinal study using UK patient registry data. Journal of Cystic Fibrosis. 2018;17(2):218-27. https://doi.org/10.1016/j.jcf.2017.11.019
• Choong E, Sauty A, Koutsokera A, Blanchon S, André P, Decosterd L. Therapeutic drug monitoring of Ivacaftor, Lumacaftor, Tezacaftor, and Elexacaftor in cystic fibrosis: where are we now? Pharmaceutics. 2022;14(8):1674. https://doi.org/10.3390/pharmaceutics14081674
• Lopes-Pacheco M. CFTR modulators: the changing face of cystic fibrosis in the era of precision medicine. Frontiers in pharmacology. 2020;10:1662. https://doi.org/10.3389/fphar.2019.01662
• Deeks ED. Lumacaftor/Ivacaftor: a review in cystic fibrosis. Drugs. 2016;76(12):1191-201. https://doi.org/10.1007/s40265-016-0611-2
• Balfour-Lynn I, King J. CFTR modulator therapies-Effect on life expectancy in people with cystic fibrosis. Paediatric respiratory reviews. 2022;42:3-8. https://doi.org/10.1016/j.prrv.2020.05.002
• Allen L, Allen L, Carr SB, Davies G, Downey D, Egan M, et al. Future therapies for cystic fibrosis. Nature communications. 2023;14(1):693. https://doi.org/10.1038/s41467-023-36244-2
• Colombo C, Foppiani A, Bisogno A, Gambazza S, Daccò V, Nazzari E, et al. Lumacaftor/ivacaftor in cystic fibrosis: effects on glucose metabolism and insulin secretion. Journal of Endocrinological Investigation. 2021;44:2213-8. https://doi.org/10.1007/s40618-021-01525-4
• Myerburg M, Pilewski JM. CFTR modulators to the rescue of individuals with cystic fibrosis and advanced lung disease. American Thoracic Society; 2021. p. 7-9. https://doi.org/10.1164/rccm.202103-0674ED
• Jennings MT, Dezube R, Paranjape S, West NE, Hong G, Braun A, et al. An observational study of outcomes and tolerances in patients with cystic fibrosis initiated on lumacaftor/ivacaftor. Annals of the American Thoracic Society. 2017;14(11):1662-6. https://doi.org/10.1513/AnnalsATS.201701-058OC
• Sawicki GS, Dasenbrook E, Fink AK, Schechter MS. Rate of uptake of ivacaftor use after US Food and Drug Administration approval among patients enrolled in the US Cystic Fibrosis Foundation Patient Registry. Annals of the American Thoracic Society. 2015;12(8):1146-52. https://doi.org/10.1513/AnnalsATS.201504-214OC
• Chhabda J, Balaji MV. Development and Validation of a New and Stability Indicating RP-HPLC Method for the Determination of Ivacaftor in Presence of Degradant Products. International Journal of Pharmacy and Pharmaceutical Sciences. 2013;5(4):607-13.
• Schneider EK, Reyes-Ortega F, Wilson JW, Kotsimbos T, Keating D, Li J, et al. Development of HPLC and LC-MS/MS methods for the analysis of ivacaftor, its major metabolites and lumacaftor in plasma and sputum of cystic fibrosis patients treated with ORKAMBI or KALYDECO. Journal of Chromatography B. 2016;1038:57-62. https://doi.org/10.1016/j.jchromb.2016.10.026
• Akram N, Umamahesh M. A New Validated RP-HPLC Method for the Determination of Lumacaftor and Ivacaftor in its Bulk and Pharmaceutical Dosage Forms. Oriental Journal of Chemistry. 2017;33(3):1492-501. https://doi.org/10.13005/ojc/330354
• Schneider EK, Reyes-Ortega F, Li J, Velkov T. Optimized LC-MS/MS method for the high-throughput analysis of clinical samples of Ivacaftor, its major metabolites, and lumacaftor in biological fluids of Cystic Fibrosis patients. Journal of visualized experiments: JoVE. 2017(128). https://doi.org/10.3791/56084
• Akram NM, Umamahesh M. A new validated RP-HPLC method for the determination of Lumacaftor and Ivacaftor in its bulk and pharmaceutical dosage forms. Oriental Journal of Chemistry. 2017;33(3):1492-501. https://doi.org/10.13005/ojc/330354
• Vonk SEM, van der Meer-Vos M, Bos LDJ, Neerincx AH, Majoor CJ, Maitland-van der Zee A-H, et al. A Quantitative Method for the Analysis of Ivacaftor, Hydroxymethyl Ivacaftor, Ivacaftor Carboxylate, Lumacaftor, and Tezacaftor in Plasma and Sputum Using LC-MS/MS and Its Clinical Applicability. Ther Drug Monit. 2020. 10.1097/ftd.0000000000000829. https://doi.org/10.1097/FTD.0000000000000829
• Özcan S, Erdoğan Uzunoğlu Ü, Levent S, Can NÖ. Liquid chromatographic determination of lumacaftor in the presence of ivacaftor and identification of five novel degradation products using high‐performance liquid chromatography ion trap time‐of‐flight mass spectrometry. Journal of Separation Science. 2023;46(17):2300228. https://doi.org/10.1002/jssc.202300228
• Özcan S, Can NÖ. Determination of ivacaftor by liquid chromatography techniques in pharmaceutical formulation with interlaboratory comparison and characterization of five novel degradation products by high‐performance liquid chromatography ion trap time‐of‐flight mass spectrometry. Journal of Separation Science. 2023:2201061. https://doi.org/10.1002/jssc.202201061