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Journals / Turkish Journal of Analytical Chemistry / 2025 / Cilt: 7 Sayı: 3

Development and validation of stability-indicating UHPLC methods for bortezomib injection solutions

Bortezomib Enjeksiyonluk Çözeltileri İçin Stabilite Göstergeli UHPLC Yöntemlerinin Geliştirilmesi ve Validasyonu

Ezgi Güneş Gürdal(Onko Koçsel İlaçları)0000-0002-1629-9495
Pages
385–393
Publication Date
2025-09-30
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

The developed method is suitable for routine quality control and stability analysis of bortezomib injection solutions.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:A rapid and robust stability-indicating Ultra-High-Performance Liquid Chromatography (UHPLC) method was developed and validated for the quantitative determination of bortezomib in injectable formulations.
📊
Key Findings & Data:The method employed a C18 column with gradient elution using a phosphate buffer and acetonitrile, achieving optimal separation within a short runtime.
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Conclusion & Impact:The developed method is suitable for routine quality control and stability analysis of bortezomib injection solutions.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:Analitik yöntem validasyonu · Bortezomib · bozunma çalışması

Abstract

A rapid and robust stability-indicating Ultra-High-Performance Liquid Chromatography (UHPLC) method was developed and validated for the quantitative determination of bortezomib in injectable formulations. The method employed a C18 column with gradient elution using a phosphate buffer and acetonitrile, achieving optimal separation within a short runtime. Linearity was confirmed across the concentration range of 2–10 mg/mL with R² > 0.999. The method was validated in accordance with ICH Q2(R2) guidelines, demonstrating specificity, precision, accuracy, robustness, and solution stability. Forced degradation studies under acidic, basic, oxidative, thermal, and photolytic stress confirmed that the method is capable of separating bortezomib from its degradation products with acceptable mass balance. The developed method is suitable for routine quality control and stability analysis of bortezomib injection solutions.

Özet

Enjekte edilebilir formülasyonlarda bortezomibin kantitatif tayini için hızlı ve sağlam bir stabilite belirleyici Ultra Yüksek Performanslı Sıvı Kromatografisi (UHPLC) yöntemi geliştirilmiş ve valide edilmiştir. Yöntemde, fosfat tamponu ve asetonitril kullanılarak gradyan elüsyonlu bir C18 kolon kullanılmış ve kısa bir çalışma süresi içinde optimum ayırma sağlanmıştır. Doğrusallık, 2-10 mg/mL konsantrasyon aralığında R² > 0,999 ile doğrulanmıştır. Yöntem, ICH Q2(R2) yönergelerine uygun olarak doğrulanmış ve özgüllük, kesinlik, doğruluk, sağlamlık ve çözelti kararlılığı göstermiştir. Asidik, bazik, oksidatif, termal ve fotolitik stres altında zorla bozunma çalışmaları, yöntemin bortezomibi bozunma ürünlerinden kabul edilebilir kütle dengesi ile ayırabildiğini doğrulamıştır. Geliştirilen yöntem, bortezomib enjeksiyon çözeltilerinin rutin kalite kontrol ve stabilite analizleri için uygundur.

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Cite This Article

Gürdal, E. G. (2025). Development and validation of stability-indicating UHPLC methods for bortezomib injection solutions. Turkish Journal of Analytical Chemistry, Cilt: 7 Sayı: 3, 385–393. https://doi.org/10.51435/turkjac.1718922

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References (32)

  1. X. Ling, D. Calinski, A.A. Chanan-Khan, M. Zhou, F. Li, Cancer cell sensitivity to bortezomib is associated with survivin expression and p53 status but not cancer cell types, Journal of Experimental & Clinical Cancer Research, 29, 2010, 8.
  2. S.P. Shah, A.K. Nooka, D.L. Jaye, N.J. Bahlis, S. Lonial, L.H. Boise, Bortezomib-induced heat shock response protects multiple myeloma cells and is activated by heat shock factor 1 serine 326 phosphorylation, Oncotarget, 7, 2016, 59727.
  3. A. Ariwoola, E.A.M. Elagab, T. Fardous, S. Oyewale, S. Parisi, H. Williams, A.M. Shediwah, I.A. Mahmoud, R. Khillan, Bortezomib-Induced Bilateral Eye Swelling and Cutaneous Adverse Reaction in a Patient with Plasma Cell Leukemia—A Case Report, Case Rep Clin Med, 12, 2023, 452-456.
  4. T.C. Kouroukis, F.G. Baldassarre, A.E. Haynes, K. Imrie, D.E. Reece, M.C. Cheung, Bortezomib in Multiple Myeloma: Systematic Review and Clinical Considerations, Curr Oncol, 21, 2014, 573-603.
  5. P.G. Richardson, P. Sonneveld, M.W. Schuster, D. Irwin, E.A. Stadtmauer, T. Facon, J.-L. Harousseau, D. Ben-Yehuda, S. Lonial, J.-F. San Miguel, J.D. Cavenagh, K.C. Anderson, Safety and efficacy of bortezomib in high-risk and elderly patients with relapsed multiple myeloma, Br J Haematol, 137, 2007, 429-435.
  6. S. Jagannath, A. Roy, J.K. Kish, D. Globe, O. Lunacsek, M.T. Eaddy, E.T. Kuriakose, J. Willey, D. Siegel, Progression-Free Survival in Third-Line Treatment of Relapsed/Refractory Multiple Myeloma Among Patients with Who Have Received Prior Bortezomib and Immunomodulatory Drugs, Blood, 126, 2015, 3311.
  7. Y. Miyamoto, S. Nakagawa, O. Wada-Hiraike, T. Seiki, M. Tanikawa, H. Hiraike, K. Sone, K. Nagasaka, K. Oda, K. Kawana, K. Nakagawa, T. Fujii, T. Yano, S. Kozuma, Y. Taketani, Sequential effects of the proteasome inhibitor bortezomib and chemotherapeutic agents in uterine cervical cancer cell lines, Oncol Rep, 29, 2013, 51-57.
  8. A.J. Ocean, P. Christos, J.A. Sparano, M.A. Shah, R.K. Yantiss, J. Cheng, J. Lin, M. Papetti, D. Matulich, F. Schnoll-Sussman, C. Besanceney-Webler, J. Xiang, M. Ward, K.T. Dilts, R. Keresztes, S. Holloway, E.X. Chen, J.J. Wright, M.E. Lane, Phase II trial of bortezomib alone or in combination with irinotecan in patients with adenocarcinoma of the gastroesophageal junction or stomach, Invest New Drugs, 32, 2014, 542-548.
  9. A.K. Nooka, J.L. Kaufman, M. Behera, A. Langston, E.K. Waller, C.R. Flowers, C. Gleason, L.H. Boise, S. Lonial, Bortezomib-containing induction regimens in transplant-eligible myeloma patients, Cancer, 119, 2013, 4119-4128.
  10. P.G. Richardson, M. Alsina, D. Weber, S.E. Coutre, S. Lonial, C. Gasparetto, S. Mukhopadhyay, M. Ondovik, M. Khan, C. Paley, R. Schlossman, PANORAMA 2: Panobinostat Combined with Bortezomib and Dexamethasone in Patients with Relapsed and Bortezomib-Refractory Multiple Myeloma, Blood, 120, 2012, 1852.
  11. M.Y. Murray, L. Zaitseva, M.J. Auger, J.I. Craig, D.J. MacEwan, S.A. Rushworth, K.M. Bowles, Ibrutinib inhibits BTK-driven NF-κB p65 activity to overcome bortezomib-resistance in multiple myeloma, Cell Cycle, 14, 2015, 2367-2375.
  12. J.-S. Ahn, S.-H. Jung, D.-H. Yang, S.-Y. Bae, Y.-K. Kim, H.-J. Kim, J.-J. Lee, Patterns of Relapse or Progression After Bortezomib-Based Salvage Therapy in Patients With Relapsed/Refractory Multiple Myeloma, Clin Lymphoma Myeloma Leuk, 14, 2014, 389-394.
  13. E.I. El-Kimary, M.A.A. Ragab, A Validated High-Performance Thin-Layer Chromatographic Method for the Assay of Two Binary Mixtures Containing Omeprazole or Its Isomer Esomeprazole in Pharmaceutical Dosage Forms, J Planar Chromatogr Mod TLC, 28, 2015, 74-82.
  14. M. Thummar, P.N. Patel, G. Samanthula, S. Ragampeta, Stability-indicating assay method for acotiamide: Separation, identification and characterization of its hydroxylated and hydrolytic degradation products along with a process-related impurity by ultra-high-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry, Rapid Commun Mass Spectrom, 31, 2017, 1813-1824.
  15. F.F. Farias, V.A.P. Martins, H.M. Yano, L.M. Trujillo, E. Pinto, Forced degradation studies to identify organic impurities in pharmaceuticals: a Brazilian perspective, Rev Cienc Farm Basica Apl, 42, 2021, 1-13.
  16. M. Sharma, M. Murugesan, Forced Degradation Study an Essential Approach to Develop Stability Indicating Method, J Chromatogr Sep Tech, 08, 2017.
  17. N. Batrawi, H. Naseef, F. Al-Rimawi, Development and Validation of a Stability-Indicating HPLC Method for the Simultaneous Determination of Florfenicol and Flunixin Meglumine Combination in an Injectable Solution, J Anal Methods Chem, 2017, 1529280.
  18. B. Dabhi, Y. Jadeja, M. Patel, H. Jebaliya, D. Karia, A. Shah, Method Development and Validation of a Stability-Indicating RP-HPLC Method for the Quantitative Analysis of Dronedarone Hydrochloride in Pharmaceutical Tablets, Sci Pharm, 81, 2013, 115-122.
  19. C. Gita, K. Krishna, A review of HPLC technique covering its pharmaceutical, environmental, forensic, clinical and other applications, Int J Pharm Chem Anal, 6, 2019, 27-39.
  20. W. Yang, X. Yang, F. Shi, Z. Liao, Y. Liang, L. Yu, R. Wang, Q. Li, K. Bi, Qualitative and quantitative assessment of related substances in the Compound Ketoconazole and Clobetasol Propionate Cream by HPLC-TOF-MS and HPLC, J Pharm Anal, 9, 2019, 156-162.
  21. N. Abdullah, F. Karamat, D. Qamar, M. Abbas, A. Khan, N. Ullah, Development and validation of RP-HPLC method for simultaneous quantification of sulfacetamide sodium and prednisolone sodium phosphate, Acta Pol Pharm, 76, 2019, 37-47.
  22. M. Finšgar, A. Perva-Uzunalić, H. Behr, N. Ledinek, Ž. Knez, Z. Novak, An Improved Reversed-Phase High-Performance Liquid Chromatography Method for the Analysis of Related Substances of Prednisolone in Active Ingredient, ACS Omega, 5, 2020, 7987-8000.
  23. S. Rao, M. Srinivasarao, G. Ramu, C. Rambabu, UV visible spectrophotometric determination of bortezomib in its bulk and formulation dosage forms, Der Pharm Lett, 4, 2012, 720-727
  24. S.B. Najana, H.B. Bollikolla, Determination of enantiomer impurity in Bortezomib lyo injection formulation by using normal-phase liquid chromatography, Future J Pharm Sci, 7, 2021, 8.
  25. Á. Gómez, M.C. Benéitez García, N. Barrueco, M.A. Lucena-Campillo, E. López-Lunar, B. García-Díaz, M. Vicario-de-la-Torre, I. Escobar-Rodríguez, M.E. Gil-Alegre, Physicochemical stability of bortezomib solutions for subcutaneous administration, Sci Rep, 14, 2024, 8975.
  26. W. Dong, X. Yu, J. Wang, Q. Sui, Is it the appropriate syringe filter? The loss of PPCPs during filtration by syringe filter, Water Emerg Contam Nanoplastics, 1, 2022,.
  27. P. Marillier, N. Adams, S. Baertschi, J.M. Campbell, C. Foti, J.R. Franca, S. Hicks, D. Kotoni, C. Laue, S. Marden, L. Meng, A.C. de O. Santos, M. Ultramari, A.V. Cleempoe, C. Wang, T. Zelesky, Z. Huang, Liquid Chromatographic Peak Purity Assessments in Forced Degradation Studies: An Industry Perspective, LCGC Int, 2024.
  28. J.T. Lawler, M. Lesslie, C.E. Randstrom, Y. Zhao, Z.S. Breitbach, A Standardized 2D-LC Screening Platform for Peak Purity Determination in Pharmaceutical Analysis, LCGC N Am, 2023.
  29. J.K. Rao, B. Mohan, N. Venugopal, M. Mohan, R. Malla, A validated reverse phase stability-indicating HPLC method for bortezomib in the presence of degradation products and its process-related impurities, Int J Pharm Chem, 3, 2016, 150-161.
  30. A. Beckett, The Importance of The ‘Hydroxylamıne Metabolic Route’ In Pharmacology, Toxicology and Pharmacokınetıcs, 1973, 139-143.
  31. FDA, Guidance for Industry Process Validation: General Principles and Practices Guidance for Industry, 2011, 800-835.
  32. E.M. Agency, ICH Q2(R2) Validation of analytical procedures - Scientific guideline | European Medicines Agency (EMA), 2024.