STRATEGIC QBD IMPLEMENTATION IN RPHPLC-PDA METHOD FOR SIMULTANEOUS QUANTIFICATION OF CYSTIC FIBROSIS DRUGS TEZACAFTOR AND IVACAFTOR
Öz
Objective: A novel RP-HPLC PDA method was developed using a Quality by Design (QbD) approach for the simultaneous quantification of Tezacaftor and Ivacaftor medications employed in the management of cystic fibrosis.
Material and Method: Optimization was performed by Central Composite Design by selecting mobile phase ratio of methanol, pH of buffer and flow rate as factors and evaluating responses namely retention time and tailing factor. This technique makes use of an Inertial ODS C18 column (250 x 4.6 mm, 5 μm particle size) in conjunction with a Waters module fitted with a photo diode array detector. The chromatographic conditions including a flow rate of 1.0 ml/min, a mobile phase composed of methanol and buffer in a 45:55 ratio, and a detection wavelength of 210 nm, were thoughtfully designed to effectively separate Tezacaftor and Ivacaftor.
Result and Discussion: The method demonstrated remarkable accuracy, with average recoveries of 99.69% for ivacaftor and 100.06% for tezacaftor. The % assay results for system suitability, method precision, and intermediate precision consistently fell within the range of 99.91% to 100.37%. Linearity data exhibited correlation coefficient values of one for both Tezacaftor and Ivacaftor. The LOD and LOQ values for Tezacaftor and Ivacaftor were determined to be 0.56, 0.57, 1.69, and 1.74, respectively. The results obtained from the validation parameters demonstrate that this RP-HPLC method, developed using the QbD approach, is robust and dependable. It serves as a valuable tool for routine analysis and plays a pivotal role in bioanalytical and bioequivalence research within the realm of cystic fibrosis treatment. This method ensures precise and accurate quantification of Tezacaftor and Ivacaftor in combination tablet formulations.
Anahtar Kelimeler
Central composite design ivacaftor method development method validation RP-HPLC tezacaftor
Kaynakça
- 1. National Center for Biotechnology Information Web site. (2024). PubChem Compound Summary for CID 72722243, Symkevi. Retrieved March 25, 2024, from https://pubchem.ncbi.nlm.nih.gov/. Accessed date: 25.03.2024.
- 2. Wikipedia Web site. (2024). Retrieved March 25, 2024, from https://en.wikipedia.org/. Accessed date: 25.03.2025.
- 3. Tripathi, K.D. (2018). Essentials of medical pharmacology. Jaypee Brothers Medical Publishers, 539-550.
- 4. PubMed Web site (2025). Retrieved March 25, 2025, from https://pubmed.ncbi.nlm.nih.gov/30489718/. Accessed date: 25.03.2025.
- 5. ICH Topic Q8 (R2), “ICH harmonized tripartite guideline,” in Proceedings of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH ’09), Pharmaceutical Development. 2009.
- 6. Bhattacharyya I, Bhattacharyya SP, and Sen S (2010). Reverse phase high-performance chromatographic liquid system for Tezacaftor hydrochloride analysis in pharmaceutical dose type, International Pharmacy and Technology Review, vol.2, pp.224-232.
- 7. Shivaradha, B., Rani, S.S. (2022). RP-HPLC method development and validation for the simultaneous determination of elexacaftor, ivacator and tezacaftor in pharmaceutical dosage forms. World Journal of Pharmaceutical Sciences, 12-21. [CrossRef]
- 8. Priyadarshini, G.I., Mounika, V., Anjani, G., Sowmya, B. (2020). Stability indicating RP-HPLC method development and validation for the simultaneous estimation of tezacaftor and ıvacaftor in bulk and pharmaceutical dosage form. Asian Journal of Pharmaceutical Analysis, 10(1), 19-26. [CrossRef]
- 9. Ramanjaneyulu, K.V., Ramana, K.V., Rao, M.P. (2020). Stability indicating LC method development and validation for the simultaneous analysis of cystic fibrosis drugs-ivacaftor and tezacaftor in pharmaceutical formulations. Research Journal of Pharmacy and Technology, 13(5), 2076-2080.
- 10. Kiranjyothi, R., Balakrishnan, M., Chandrasekhar, K.B. (2018). Method development and validation for the stability indicating simultaneous estimation of tezacaftor and ivacaftor in bulk and its dosage forms. International Journal of Pharmaceutical Research, 10(4), 173.
- 11. Donakonda, M., Indrakanti, S., Pasala, P.K., Desari, M., Kammari, S. (2021). A rapid RP-HPLC method for the simultaneous estimation of Ivacaftor and Tezacaftor and in silico study of their metabolitic products. Future Journal of Pharmaceutical Sciences, 7, 1-14. [CrossRef]
- 12. Singh, N., Bansal, P., Maithani, M., Chauhan, Y. (2020). Development and validation of a novel stability-indicating RP-HPLC method for simultaneous determination of tezacaftor and ivacaftor in fixed dose combination. Journal of Chromatographic Science, 58(4), 346-354. [CrossRef]
- 13. Kandula R.K., Sundararajan R. (2020). Stability indicating RP-HPLC method development and validation for the simultaneous estimation of tezacaftor, ivacaftor and elexacaftor in bulk and its combined dosage form. Journal of Global Trends in Pharmaceutical Sciences, 11 (4), 8552-8557.
- 14. Sane, R.T., Francis, M., Khedkar, S., Menezrs, A., Moghe, A., Patil, P. (2003). Gas chromatographic determination of bupropion hydrochloride from its pharmaceutical formulations. Indian drugs, 40(4), 231-233.
- 15. Ravali, T., Marakatham, S., Kumar, M.S., Valli, R.V. (2019). Analytical method development and validation of tezacaftor and ıvacaftor by RPHPLC methodin bulk and marketed formulation. International Journal of Pharmacy and Biological Sciences, 9(4), 67-73.
- 16. Kumari, P.V.K., Yarraguntla, S.R., Sharmila, M., Gulibindala, E. (2021). Application of box-behnken design for formulation parameters of eslicarbazepine tablets. Indian Journal of Pharmaceutical Sciences, 83(3). [CrossRef]
- 17. Swathi, S., Kumar, H.T., Rao, P.K. (2015). Validated RP-HPLC method for simultaneous determination of rosuvastatin calcium and ezetimibe in pharmaceutical dosage form. Int. J. Pharm. And Pharm. sci, 7(4), 209-213.
- 18. Rao, K.V., Tanuja, M., Rao, Y.S., Kumar, T.H. (2015). Development and validation of spectrophotometric methods for estimation of zileuton in bulk and its dosage form. International Journal Chemical Sciences, 13(2), 714-24.
- 19. Lakshmi, G.T., Rao, Y.S., Rao, K., Prasada, V., Kumar, T.H. (2015). RP-HPLC method for estimation of atomoxetine hydrochloride in bulk and pharmaceutical dosage form. Research Journal Of Pharmaceutical Biological and Chemical Sciences, 6(2), 1208-1214.
- 20. Lakshmi, T.G., Rao, S.Y., Rao, V.P.K., Kumar, H.T. (2015). Visible spectrophotometric methods for the estimation of orlistat in bulk and pharmaceutical dosage form. Journal of Pharmaceutical Sciences and Research, 7(3), 155.
- 21. Siridevi, M.P., Hemant, K.T., Srinivasa, R.Y., Varaprasad, R.K. (2019). Simultaneous spectrophotometric estimation of amlodipine besylate and Perindopril Erbumine in tablet Formulation. Research Journal of Pharmacy and Technology, 12(12), 6101-6106. [CrossRef]
- 22. Srinivasarao, Y., Kumar, T.H., Chiranjivi, P., Rao, K.V. (2021). Simultaneous estimation of solifenacin succinate and tamsulosin hydrochloride in combined dosage form by using first order derivative spectrophotometric method. Indian Journal of Pharmaceutical Sciences, 83(2), 331-335. [CrossRef]
- 23. Anusha, G., Nargiz, S., Sireesha, A., Poojitha, K., Rao, K.V., Rao, Y.S. (2024). Green solvent-based UV spectrophotometric technique for quantifying molnupiravir in bulk and pharmaceutical formulation. Research Journal of Pharmacy and Technology, 17(11), 5210-5214. [CrossRef]
- 24. Gandi, A., Dudi, P.K., Pantala, E.S., Yarguntla, S.R. (2024). A comprehensive new approach to method development and validation of encorafenib using uv spectroscopy in bulk and pharmaceutical formulation. Hacettepe University Journal of the Faculty of Pharmacy, 44(4), 318-327. [CrossRef]
- 25. Gandi, A., Dudi, P.K., Pantala, E.S., Challa, G.N. (2024). Analyzing paxlovid: Examining its properties, characteristics, and analytical and bio‐analytical methods-A comprehensive review. Separation Science Plus, 7(12), e202400117. [CrossRef]
- 26. Gandi, A., Rao, N.K., Anusha, G., Preethi, G., Mounika, D. (2020). Method development and validation of rupatadine fumarate in bulk by UV spectroscopy. International Journal of Ayurveda and Pharma Research, 51-54.
- 27. International Conference on Technical Requirement Harmonization for Pharmaceuticals for Human Use. (2005). Registration.Validation of analytical techniques:text and approach1-13 in ICHQ2(R1).
- 28. Analytical Techniques and Method Validation: Chemistry, Performance, and Controls. (2000) FDA. 65: 776-777 in the Federal Register.
- 29. Theoretical Methodological Validation (1996). Methodology, ICH Harmonized Tripartite Recommendations, Federal Register, Q2B(R1), 1-8.
- 30. Vogt, F.G., Kord, A.S. (2011). Development of quality-by-design analytical methods. Journal Of Pharmaceutical Sciences, 100(3), 797-812. [CrossRef]
KİSTİK FİBROZİS İLAÇLARI TEZACAFTOR VE IVACAFTOR'UN EŞ ZAMANLI KANTİFİKASYONU İÇİN RPHPLC-PDA YÖNTEMİNDE STRATEJİK QBD UYGULAMASI
Öz
Amaç: Kistik fibrozis tedavisinde kullanılan Tezacaftor ve Ivacaftor ilaçlarının eş zamanlı ölçümü için Tasarıma Göre Kalite (QbD) yaklaşımı kullanılarak yeni bir RP-HPLC PDA yöntemi geliştirildi.
Gereç ve Yöntem: Optimizasyon, metanolün mobil faz oranı, tamponun pH'ı ve akış hızının faktör olarak seçilmesi ve tepkilerin, yani alıkonma süresi ve kuyruk faktörünün değerlendirilmesi yoluyla Merkezi Bileşik Tasarım ile gerçekleştirildi. Bu teknik, bir foto diyot dizisi dedektörü ile donatılmış bir Waters modülü ile birlikte bir Inertial ODS C18 kolonundan (250 x 4,6 mm, 5 μm parçacık boyutunda) yararlanır. 1.0 ml/dak'lık bir akış hızı, 45:55 oranında metanol ve tampondan oluşan bir mobil faz ve 210 nm'lik bir tespit dalga boyunu içeren kromatografik koşullar, Tezacaftor ve Ivacaftor'u etkili bir şekilde ayırmak için iyi bir şekilde tasarlanmıştır.
Sonuç ve Tartışma: Yöntem, ivacaftor için %99.69 ve tezacaftor için %100.06'lık ortalama geri kazanımlarla dikkate değer bir doğruluk gösterdi. Sistem uygunluğu, yöntem kesinliği ve ara kesinlik için % miktar tayini sonuçları sürekli olarak %99.91 ile %100.37 aralığında tespit edildi. Doğrusallık verileri, hem Tezacaftor hem de Ivacaftor için bir korelasyon katsayısı değeri gösterdi. Tezacaftor ve Ivacaftor için LOD ve LOQ değerleri sırasıyla 0.56, 0.57, 1.69 ve 1.74 olarak belirlendi. Doğrulama parametrelerinden elde edilen sonuçlar, QbD yaklaşımı kullanılarak geliştirilen bu RP-HPLC yönteminin sağlam ve güvenilir olduğunu göstermektedir. Rutin analizler için bu teknik değerli bir araç olarak hizmet eder ve kistik fibroz tedavisi alanında biyoanalitik ve biyoeşdeğerlik araştırmalarında önemli bir rol oynar. Bu yöntem, kombinasyon tablet formülasyonlarında Tezacaftor ve Ivacaftor'un kesin ve doğru miktarının belirlenmesini sağlar.
Anahtar Kelimeler
Merkezi kompozit tasarım ivacaftor RP-HPLC tezacaftor yöntem geliştirme yöntem validasyonu
Kaynakça
- 1. National Center for Biotechnology Information Web site. (2024). PubChem Compound Summary for CID 72722243, Symkevi. Retrieved March 25, 2024, from https://pubchem.ncbi.nlm.nih.gov/. Accessed date: 25.03.2024.
- 2. Wikipedia Web site. (2024). Retrieved March 25, 2024, from https://en.wikipedia.org/. Accessed date: 25.03.2025.
- 3. Tripathi, K.D. (2018). Essentials of medical pharmacology. Jaypee Brothers Medical Publishers, 539-550.
- 4. PubMed Web site (2025). Retrieved March 25, 2025, from https://pubmed.ncbi.nlm.nih.gov/30489718/. Accessed date: 25.03.2025.
- 5. ICH Topic Q8 (R2), “ICH harmonized tripartite guideline,” in Proceedings of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH ’09), Pharmaceutical Development. 2009.
- 6. Bhattacharyya I, Bhattacharyya SP, and Sen S (2010). Reverse phase high-performance chromatographic liquid system for Tezacaftor hydrochloride analysis in pharmaceutical dose type, International Pharmacy and Technology Review, vol.2, pp.224-232.
- 7. Shivaradha, B., Rani, S.S. (2022). RP-HPLC method development and validation for the simultaneous determination of elexacaftor, ivacator and tezacaftor in pharmaceutical dosage forms. World Journal of Pharmaceutical Sciences, 12-21. [CrossRef]
- 8. Priyadarshini, G.I., Mounika, V., Anjani, G., Sowmya, B. (2020). Stability indicating RP-HPLC method development and validation for the simultaneous estimation of tezacaftor and ıvacaftor in bulk and pharmaceutical dosage form. Asian Journal of Pharmaceutical Analysis, 10(1), 19-26. [CrossRef]
- 9. Ramanjaneyulu, K.V., Ramana, K.V., Rao, M.P. (2020). Stability indicating LC method development and validation for the simultaneous analysis of cystic fibrosis drugs-ivacaftor and tezacaftor in pharmaceutical formulations. Research Journal of Pharmacy and Technology, 13(5), 2076-2080.
- 10. Kiranjyothi, R., Balakrishnan, M., Chandrasekhar, K.B. (2018). Method development and validation for the stability indicating simultaneous estimation of tezacaftor and ivacaftor in bulk and its dosage forms. International Journal of Pharmaceutical Research, 10(4), 173.
- 11. Donakonda, M., Indrakanti, S., Pasala, P.K., Desari, M., Kammari, S. (2021). A rapid RP-HPLC method for the simultaneous estimation of Ivacaftor and Tezacaftor and in silico study of their metabolitic products. Future Journal of Pharmaceutical Sciences, 7, 1-14. [CrossRef]
- 12. Singh, N., Bansal, P., Maithani, M., Chauhan, Y. (2020). Development and validation of a novel stability-indicating RP-HPLC method for simultaneous determination of tezacaftor and ivacaftor in fixed dose combination. Journal of Chromatographic Science, 58(4), 346-354. [CrossRef]
- 13. Kandula R.K., Sundararajan R. (2020). Stability indicating RP-HPLC method development and validation for the simultaneous estimation of tezacaftor, ivacaftor and elexacaftor in bulk and its combined dosage form. Journal of Global Trends in Pharmaceutical Sciences, 11 (4), 8552-8557.
- 14. Sane, R.T., Francis, M., Khedkar, S., Menezrs, A., Moghe, A., Patil, P. (2003). Gas chromatographic determination of bupropion hydrochloride from its pharmaceutical formulations. Indian drugs, 40(4), 231-233.
- 15. Ravali, T., Marakatham, S., Kumar, M.S., Valli, R.V. (2019). Analytical method development and validation of tezacaftor and ıvacaftor by RPHPLC methodin bulk and marketed formulation. International Journal of Pharmacy and Biological Sciences, 9(4), 67-73.
- 16. Kumari, P.V.K., Yarraguntla, S.R., Sharmila, M., Gulibindala, E. (2021). Application of box-behnken design for formulation parameters of eslicarbazepine tablets. Indian Journal of Pharmaceutical Sciences, 83(3). [CrossRef]
- 17. Swathi, S., Kumar, H.T., Rao, P.K. (2015). Validated RP-HPLC method for simultaneous determination of rosuvastatin calcium and ezetimibe in pharmaceutical dosage form. Int. J. Pharm. And Pharm. sci, 7(4), 209-213.
- 18. Rao, K.V., Tanuja, M., Rao, Y.S., Kumar, T.H. (2015). Development and validation of spectrophotometric methods for estimation of zileuton in bulk and its dosage form. International Journal Chemical Sciences, 13(2), 714-24.
- 19. Lakshmi, G.T., Rao, Y.S., Rao, K., Prasada, V., Kumar, T.H. (2015). RP-HPLC method for estimation of atomoxetine hydrochloride in bulk and pharmaceutical dosage form. Research Journal Of Pharmaceutical Biological and Chemical Sciences, 6(2), 1208-1214.
- 20. Lakshmi, T.G., Rao, S.Y., Rao, V.P.K., Kumar, H.T. (2015). Visible spectrophotometric methods for the estimation of orlistat in bulk and pharmaceutical dosage form. Journal of Pharmaceutical Sciences and Research, 7(3), 155.
- 21. Siridevi, M.P., Hemant, K.T., Srinivasa, R.Y., Varaprasad, R.K. (2019). Simultaneous spectrophotometric estimation of amlodipine besylate and Perindopril Erbumine in tablet Formulation. Research Journal of Pharmacy and Technology, 12(12), 6101-6106. [CrossRef]
- 22. Srinivasarao, Y., Kumar, T.H., Chiranjivi, P., Rao, K.V. (2021). Simultaneous estimation of solifenacin succinate and tamsulosin hydrochloride in combined dosage form by using first order derivative spectrophotometric method. Indian Journal of Pharmaceutical Sciences, 83(2), 331-335. [CrossRef]
- 23. Anusha, G., Nargiz, S., Sireesha, A., Poojitha, K., Rao, K.V., Rao, Y.S. (2024). Green solvent-based UV spectrophotometric technique for quantifying molnupiravir in bulk and pharmaceutical formulation. Research Journal of Pharmacy and Technology, 17(11), 5210-5214. [CrossRef]
- 24. Gandi, A., Dudi, P.K., Pantala, E.S., Yarguntla, S.R. (2024). A comprehensive new approach to method development and validation of encorafenib using uv spectroscopy in bulk and pharmaceutical formulation. Hacettepe University Journal of the Faculty of Pharmacy, 44(4), 318-327. [CrossRef]
- 25. Gandi, A., Dudi, P.K., Pantala, E.S., Challa, G.N. (2024). Analyzing paxlovid: Examining its properties, characteristics, and analytical and bio‐analytical methods-A comprehensive review. Separation Science Plus, 7(12), e202400117. [CrossRef]
- 26. Gandi, A., Rao, N.K., Anusha, G., Preethi, G., Mounika, D. (2020). Method development and validation of rupatadine fumarate in bulk by UV spectroscopy. International Journal of Ayurveda and Pharma Research, 51-54.
- 27. International Conference on Technical Requirement Harmonization for Pharmaceuticals for Human Use. (2005). Registration.Validation of analytical techniques:text and approach1-13 in ICHQ2(R1).
- 28. Analytical Techniques and Method Validation: Chemistry, Performance, and Controls. (2000) FDA. 65: 776-777 in the Federal Register.
- 29. Theoretical Methodological Validation (1996). Methodology, ICH Harmonized Tripartite Recommendations, Federal Register, Q2B(R1), 1-8.
- 30. Vogt, F.G., Kord, A.S. (2011). Development of quality-by-design analytical methods. Journal Of Pharmaceutical Sciences, 100(3), 797-812. [CrossRef]
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Eczacılıkta Analitik Kimya |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Erken Görünüm Tarihi | 2 Mayıs 2025 |
| Yayımlanma Tarihi | 19 Mayıs 2025 |
| Gönderilme Tarihi | 11 Eylül 2024 |
| Kabul Tarihi | 14 Mart 2025 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 49 Sayı: 2 |
Kaynak Göster
Kapsam ve Amaç
Ankara Üniversitesi Eczacılık Fakültesi Dergisi, açık erişim, hakemli bir dergi olup Türkçe veya İngilizce olarak farmasötik bilimler alanındaki önemli gelişmeleri içeren orijinal araştırmalar, derlemeler ve kısa bildiriler için uluslararası bir yayım ortamıdır. Bilimsel toplantılarda sunulan bildiriler supleman özel sayısı olarak dergide yayımlanabilir. Ayrıca, tüm farmasötik alandaki gelecek ve önceki ulusal ve uluslararası bilimsel toplantılar ile sosyal aktiviteleri içerir.