Araştırma Makalesi
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QUALITY BY DESIGN ASSISTED RP-HPLC METHOD FOR ESTIMATION OF TERIFLUNOMIDE AND ITS PROCESS IMPURITIES IN DRUG SUBSTANCE

Yıl 2024, Cilt: 48 Sayı: 3, 962 - 974, 10.09.2024
https://doi.org/10.33483/jfpau.1464923

Öz

Objective: In this research, a validated RP-HPLC method for analyzing teriflunomide drug substance and its associated process-related impurities was developed with the assistance of the Quality by Design (QbD) approach.
Material and Method: The QbD methodology employs statistical design of experiments to establish a robust method within a defined "design space." This design space outlines the experimental parameters' range within which alterations will not significantly impact the results. Chromatographic separation was done on HPLC system connected to a PDA detector, and the column used was the C18 YmC-Triart with specifications of 125 cm x 4.0 mm x 5.0 μm. The optimized mobile phase consisted of 0.5% triethylamine buffer with pH 4.0 (± 0.05) and acetonitrile in a 65:35 v/v ratio, flow rate of 1.0 ml/min. Detection wavelength of 210 nm.
Result and Discussion: The developed RP-HPLC method successfully achieved high resolution, specificity, linearity, precision, accuracy, and robustness in quantifying both teriflunomide and its impurities simultaneously. Using a design of experiments (DoE) approach, critical method parameters were systematically identified and optimized, ensuring accurate and precise determination of impurity levels across the drug substance lifecycle. This validated method provides a thorough approach to ensuring the quality and safety of teriflunomide drug substances by delivering reliable data on impurity profiles. By applying Quality by Design (QbD) principles, not only does the method enhance understanding of the analytical process, but it also supports ongoing improvement and lifecycle management of the procedure.

Kaynakça

  • 1. Parekh, J.M., Vaghela, R.N., Sutariya, D.K., Sanyal, M., Yadav, M., Shrivastav, P.S. (2010). Chromatographic separation and sensitive determination of teriflunomide, an active metabolite of leflunomide in human plasma by liquid chromatography-tandem mass spectrometry. Journal of Chromatography B, 878(24), 2217-2225. [CrossRef]
  • 2. Pandey, S., Mahtab, A., Singh, A., Ahmad, F.J., Aqil, M., Talegaonkar, S. (2018). Development and validation of stability indicating reversed‐phase liquid chromatographic method for simultaneous quantification of methotrexate and teriflunomide in nanoparticles and marketed formulation. Biomedical Chromatography, 32(12), e4372. [CrossRef]
  • 3. Suneetha, A., Raja, R.K. (2016). Comparison of LC‐UV and LC-MS methods for simultaneous determination of teriflunomide, dimethyl fumarate and fampridine in human plasma: Application to rat pharmacokinetic study. Biomedical Chromatography, 30(9), 1371-1377. [CrossRef]
  • 4. Rakhila, H., Rozek, T., Hopkins, A., Proudman, S., Cleland, L., James, M., Wiese, M. (2011). Quantitation of total and free teriflunomide (A77 1726) in human plasma by LC-MS/MS. Journal of Pharmaceutical and Biomedical Analysis, 55(2), 325-331. [CrossRef]
  • 5. Rule, G.S., Rockwood, A.L., Johnson-Davis, K.L. (2019). LC-MS/MS Method for the quantification of the leflunomide metabolite, teriflunomide, in human serum/plasma. LC-MS in Drug Analysis: Methods and Protocols, 75-83. [CrossRef]
  • 6. Koppisetty, B.R.B., Yejella, R.P., Pawar, A.K.M., Yarraguntla, S.R., Kollabathula, V.R., Dadi, V., Naidu, C.G. (2023). Development of a validated RP-HPLC assay method for quantitative separation of Teriflunomide and its process-related impurities in bulk drugs. Journal of Applied Pharmaceutical Science, 13(1), 028-033. [CrossRef]
  • 7. Nadella, N.P., Ratnakaram, V.N., Srinivasu, N. (2017). Quality-by-design-based development and validation of a stability-indicating UPLC method for quantification of teriflunomide in the presence of degradation products and its application to in-vitro dissolution. Journal of Liquid Chromatography & Related Technologies, 40(10), 517-527. [CrossRef]
  • 8. Suneetha, A., Raja, R.K. (2016). Comparison of LC‐UV and LC-MS methods for simultaneous determination of teriflunomide, dimethyl fumarate and fampridine in human plasma: Application to rat pharmacokinetic study. Biomedical Chromatography, 30(9), 1371-1377. [CrossRef]
  • 9. Koppisetty, B.R.B., Prasad, Y.R., Amgoth, K.M.P., Yarraguntla, S.R., Dadı, V., Tatapudı, H.K. (2023). Utility of quality by design approach in rp-hplc method development for quantification of lamivudine and effavirenz in combination formulation. Journal of Faculty of Pharmacy of Ankara University, 47(2), 625-636. [CrossRef]
  • 10. Koppisetty, B.R.B., Tatapudi, H.K., Dadi, V., Gayathri, P.R., Komali, P., Challa, G.N., Yarraguntla, S.R. (2023). QbD based RP-HPLC method for simultaneous determination of a emtricitabine, tenofovir diproxil fumarate and efavirenz in tablet dosage form-an application to stability indicating assay. Analytical Chemistry Letters, 13(3), 267-288. [CrossRef]
  • 11. Koppisetty, B.R.B., Yejella, R.P., Pawar, A., Yarraguntla, S.R., Dadi, V., Naidua, C.G. (2023). A sensitive azeotropic solvent screening head space gas chromatographic method for teriflunomide drug substance. Current Trends in Drug Discovery, Development and Delivery (CTD4-2022), 258-267. [CrossRef]
  • 12. ICH, Validation of analytical procedures, International Conference on Harmonization, IFPMA, Geneva, 1994.
  • 13. ICH, Impurities in New drug substances, International Conference on Harmonization, 20.

TERİFLUNOMİD VE İLAÇ MADDESİNİN ÜRETİMİNDEKİ SAFSIZLIKLARININ TAHMİNİ İÇİN TASARIMLA KALİTE DESTEKLİ RP-HPLC YÖNTEMİ

Yıl 2024, Cilt: 48 Sayı: 3, 962 - 974, 10.09.2024
https://doi.org/10.33483/jfpau.1464923

Öz

Amaç: Bu araştırmada, teriflunomid ilaç maddesini ve onun süreçi ile ilişkili safsızlıkları Tasarımla Kalite (QbD) yaklaşımı yardımıyla analiz etmek için doğrulanmış bir RP-HPLC yöntemi geliştirildi.
Gereç ve Yöntem: QbD metodolojisi, tanımlanmış bir "tasarım alanı" dahilinde sağlam bir yöntem oluşturmak için deneylerin istatistiksel tasarımını kullanır. Bu tasarım alanı, değişikliklerin sonuçları önemli ölçüde etkilemeyeceği deneysel parametre aralığının ana hatlarını çizer. Kromatografik ayırma, bir PDA detektörüne bağlı bir HPLC sistemi üzerinde gerçekleştirildi ve kullanılan kolon, 125 cm x 4.0 mm x 5.0 μm spesifikasyonlarına sahip C18 YmC-Triart'tı. Optimize edilmiş mobil faz, pH 4.0 (± 0.05) olan %0.5 trietilamin tamponundan ve 65:35 v/v oranında, 1.0 ml/dak akış hızında asetonitrilden oluşuyordu. 210 nm algılama dalga boyu.
Sonuç ve Tartışma: Geliştirilen RP-HPLC yöntemi, hem teriflunomidin hem de onun safsızlıklarının aynı anda ölçülmesinde yüksek çözünürlük, özgüllük, doğrusallık, kesinlik, doğruluk ve sağlamlığı başarıyla elde etti. Bir deney tasarımı (DoE) yaklaşımı kullanılarak, kritik yöntem parametreleri sistematik olarak tanımlandı ve optimize edildi; böylece ilaç maddesi yaşam döngüsü boyunca safsızlık seviyelerinin doğru ve kesin olarak belirlenmesi sağlandı. Doğrulanmış bu yöntem, safsızlık profilleri hakkında güvenilir veriler sunarak teriflunomid ilaç maddelerinin kalitesini ve güvenliğini sağlamaya yönelik kapsamlı bir yaklaşım sağlar. Tasarımla Kalite (QbD) ilkelerini uygulayarak, yöntem yalnızca analitik sürecin anlaşılmasını geliştirmekle kalmaz, aynı zamanda prosedürün sürekli iyileştirilmesini ve yaşam döngüsü yönetimini de destekler.

Kaynakça

  • 1. Parekh, J.M., Vaghela, R.N., Sutariya, D.K., Sanyal, M., Yadav, M., Shrivastav, P.S. (2010). Chromatographic separation and sensitive determination of teriflunomide, an active metabolite of leflunomide in human plasma by liquid chromatography-tandem mass spectrometry. Journal of Chromatography B, 878(24), 2217-2225. [CrossRef]
  • 2. Pandey, S., Mahtab, A., Singh, A., Ahmad, F.J., Aqil, M., Talegaonkar, S. (2018). Development and validation of stability indicating reversed‐phase liquid chromatographic method for simultaneous quantification of methotrexate and teriflunomide in nanoparticles and marketed formulation. Biomedical Chromatography, 32(12), e4372. [CrossRef]
  • 3. Suneetha, A., Raja, R.K. (2016). Comparison of LC‐UV and LC-MS methods for simultaneous determination of teriflunomide, dimethyl fumarate and fampridine in human plasma: Application to rat pharmacokinetic study. Biomedical Chromatography, 30(9), 1371-1377. [CrossRef]
  • 4. Rakhila, H., Rozek, T., Hopkins, A., Proudman, S., Cleland, L., James, M., Wiese, M. (2011). Quantitation of total and free teriflunomide (A77 1726) in human plasma by LC-MS/MS. Journal of Pharmaceutical and Biomedical Analysis, 55(2), 325-331. [CrossRef]
  • 5. Rule, G.S., Rockwood, A.L., Johnson-Davis, K.L. (2019). LC-MS/MS Method for the quantification of the leflunomide metabolite, teriflunomide, in human serum/plasma. LC-MS in Drug Analysis: Methods and Protocols, 75-83. [CrossRef]
  • 6. Koppisetty, B.R.B., Yejella, R.P., Pawar, A.K.M., Yarraguntla, S.R., Kollabathula, V.R., Dadi, V., Naidu, C.G. (2023). Development of a validated RP-HPLC assay method for quantitative separation of Teriflunomide and its process-related impurities in bulk drugs. Journal of Applied Pharmaceutical Science, 13(1), 028-033. [CrossRef]
  • 7. Nadella, N.P., Ratnakaram, V.N., Srinivasu, N. (2017). Quality-by-design-based development and validation of a stability-indicating UPLC method for quantification of teriflunomide in the presence of degradation products and its application to in-vitro dissolution. Journal of Liquid Chromatography & Related Technologies, 40(10), 517-527. [CrossRef]
  • 8. Suneetha, A., Raja, R.K. (2016). Comparison of LC‐UV and LC-MS methods for simultaneous determination of teriflunomide, dimethyl fumarate and fampridine in human plasma: Application to rat pharmacokinetic study. Biomedical Chromatography, 30(9), 1371-1377. [CrossRef]
  • 9. Koppisetty, B.R.B., Prasad, Y.R., Amgoth, K.M.P., Yarraguntla, S.R., Dadı, V., Tatapudı, H.K. (2023). Utility of quality by design approach in rp-hplc method development for quantification of lamivudine and effavirenz in combination formulation. Journal of Faculty of Pharmacy of Ankara University, 47(2), 625-636. [CrossRef]
  • 10. Koppisetty, B.R.B., Tatapudi, H.K., Dadi, V., Gayathri, P.R., Komali, P., Challa, G.N., Yarraguntla, S.R. (2023). QbD based RP-HPLC method for simultaneous determination of a emtricitabine, tenofovir diproxil fumarate and efavirenz in tablet dosage form-an application to stability indicating assay. Analytical Chemistry Letters, 13(3), 267-288. [CrossRef]
  • 11. Koppisetty, B.R.B., Yejella, R.P., Pawar, A., Yarraguntla, S.R., Dadi, V., Naidua, C.G. (2023). A sensitive azeotropic solvent screening head space gas chromatographic method for teriflunomide drug substance. Current Trends in Drug Discovery, Development and Delivery (CTD4-2022), 258-267. [CrossRef]
  • 12. ICH, Validation of analytical procedures, International Conference on Harmonization, IFPMA, Geneva, 1994.
  • 13. ICH, Impurities in New drug substances, International Conference on Harmonization, 20.
Toplam 13 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılıkta Analitik Kimya
Bölüm Araştırma Makalesi
Yazarlar

Vasudha Dadi 0000-0003-3862-0590

Saritha Medapati 0000-0003-0861-9484

Jagadeesh Kumar Baratam 0009-0000-6635-7086

Hemant Kumar Tatapudi 0000-0002-3571-7859

Gangu Naidu Challa 0000-0002-8369-7362

Srinivasa Rao Yarraguntla 0000-0002-8803-9668

Bhagavan Rajesh Babu Koppisetty 0000-0002-9576-4702

Erken Görünüm Tarihi 3 Ağustos 2024
Yayımlanma Tarihi 10 Eylül 2024
Gönderilme Tarihi 6 Nisan 2024
Kabul Tarihi 9 Temmuz 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 48 Sayı: 3

Kaynak Göster

APA Dadi, V., Medapati, S., Baratam, J. K., Tatapudi, H. K., vd. (2024). QUALITY BY DESIGN ASSISTED RP-HPLC METHOD FOR ESTIMATION OF TERIFLUNOMIDE AND ITS PROCESS IMPURITIES IN DRUG SUBSTANCE. Journal of Faculty of Pharmacy of Ankara University, 48(3), 962-974. https://doi.org/10.33483/jfpau.1464923
AMA Dadi V, Medapati S, Baratam JK, Tatapudi HK, Challa GN, Yarraguntla SR, Koppisetty BRB. QUALITY BY DESIGN ASSISTED RP-HPLC METHOD FOR ESTIMATION OF TERIFLUNOMIDE AND ITS PROCESS IMPURITIES IN DRUG SUBSTANCE. Ankara Ecz. Fak. Derg. Eylül 2024;48(3):962-974. doi:10.33483/jfpau.1464923
Chicago Dadi, Vasudha, Saritha Medapati, Jagadeesh Kumar Baratam, Hemant Kumar Tatapudi, Gangu Naidu Challa, Srinivasa Rao Yarraguntla, ve Bhagavan Rajesh Babu Koppisetty. “QUALITY BY DESIGN ASSISTED RP-HPLC METHOD FOR ESTIMATION OF TERIFLUNOMIDE AND ITS PROCESS IMPURITIES IN DRUG SUBSTANCE”. Journal of Faculty of Pharmacy of Ankara University 48, sy. 3 (Eylül 2024): 962-74. https://doi.org/10.33483/jfpau.1464923.
EndNote Dadi V, Medapati S, Baratam JK, Tatapudi HK, Challa GN, Yarraguntla SR, Koppisetty BRB (01 Eylül 2024) QUALITY BY DESIGN ASSISTED RP-HPLC METHOD FOR ESTIMATION OF TERIFLUNOMIDE AND ITS PROCESS IMPURITIES IN DRUG SUBSTANCE. Journal of Faculty of Pharmacy of Ankara University 48 3 962–974.
IEEE V. Dadi, “QUALITY BY DESIGN ASSISTED RP-HPLC METHOD FOR ESTIMATION OF TERIFLUNOMIDE AND ITS PROCESS IMPURITIES IN DRUG SUBSTANCE”, Ankara Ecz. Fak. Derg., c. 48, sy. 3, ss. 962–974, 2024, doi: 10.33483/jfpau.1464923.
ISNAD Dadi, Vasudha vd. “QUALITY BY DESIGN ASSISTED RP-HPLC METHOD FOR ESTIMATION OF TERIFLUNOMIDE AND ITS PROCESS IMPURITIES IN DRUG SUBSTANCE”. Journal of Faculty of Pharmacy of Ankara University 48/3 (Eylül 2024), 962-974. https://doi.org/10.33483/jfpau.1464923.
JAMA Dadi V, Medapati S, Baratam JK, Tatapudi HK, Challa GN, Yarraguntla SR, Koppisetty BRB. QUALITY BY DESIGN ASSISTED RP-HPLC METHOD FOR ESTIMATION OF TERIFLUNOMIDE AND ITS PROCESS IMPURITIES IN DRUG SUBSTANCE. Ankara Ecz. Fak. Derg. 2024;48:962–974.
MLA Dadi, Vasudha vd. “QUALITY BY DESIGN ASSISTED RP-HPLC METHOD FOR ESTIMATION OF TERIFLUNOMIDE AND ITS PROCESS IMPURITIES IN DRUG SUBSTANCE”. Journal of Faculty of Pharmacy of Ankara University, c. 48, sy. 3, 2024, ss. 962-74, doi:10.33483/jfpau.1464923.
Vancouver Dadi V, Medapati S, Baratam JK, Tatapudi HK, Challa GN, Yarraguntla SR, Koppisetty BRB. QUALITY BY DESIGN ASSISTED RP-HPLC METHOD FOR ESTIMATION OF TERIFLUNOMIDE AND ITS PROCESS IMPURITIES IN DRUG SUBSTANCE. Ankara Ecz. Fak. Derg. 2024;48(3):962-74.

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.