FARMASÖTİK DOZAJ FORMLARINDA ALPELİSİB MİKTAR TAYİNİ İÇİN VALİDE EDİLMİŞ YÜKSEK PERFORMANSLI SIVI KROMATOGRAFİK VE SPEKTROFOTOMETRİK YÖNTEM GELİŞTİRİLMESİ

Yıl 2025, Cilt: 49 Sayı: 2, 271 - 283, 19.05.2025

Wiem Bouali , Mariem Bouali , Asena Ayse Genc , Nevin Erk

https://doi.org/10.33483/jfpau.1579369

Öz

Amaç: Bu çalışma, Alpelisib’in (ALP) yığın ve farmasötik formlarda tayini için çevreci UV spektrofotometri, birinci derece türev spektrofotometri ve ters faz HPLC (RP-HPLC) yöntemlerini geliştirmeyi ve doğrulamayı amaçlanmıştır. Çalışma yöntemlerin çevre dostu olduğunu, doğruluklarını ve uygulanabilirliklerini değerlendirmek için GAPI ve AGREE metrikleri ile karşılaştırılmıştır.
Gereç ve Yöntem: UV spektrofotometrik ve RP-HPLC analizleri sırasıyla Shimadzu UV 1800 ve Agilent 1100 HPLC sistemleri ile gerçekleştirilmiştir. HPLC için mobil faz, %0.1 triflorasetik asit suda, asetonitril ve metanolün (50:25:25 h/h/h) karışımından oluşmaktadır. ALP tabletleri, metanol/su (50:50 h/h) içinde çözülüp filtrelendikten sonra hazırlanmış ve analiz edilmiştir. Doğrulama, ICH kılavuzlarına göre yapılmıştır.
Sonuç ve Tartışma: Geliştirilen yöntemler yüksek hassasiyet, dayanıklılık ve duyarlılık göstermiştir. UV ve HPLC yöntemleri kullanılarak ilaç formülasyonlarında ALP’nin tayini yapılmış ve doğrudan UV spektrofotometri için 0.078 μg/ml, RP-HPLC için ise 14 μg/ml olarak tespit limitlerine ulaşılmıştır. Çevreci değerlendirme, yöntemlerin sürdürülebilir farmasötik analiz için çevre dostu uyumluluğunu vurgulamaktadır.

Anahtar Kelimeler

Alpelisib, antikanser ilaç, çevreci değerlendirme, doğrulama, RP-HPLC, spektrofotometrik

DEVELOPMENT AND VALIDATION OF GREEN RP-HPLC AND SPECTROPHOTOMETRIC METHODS FOR DETERMINATION OF ALPELISIB IN BULK AND PHARMACEUTICAL DOSAGE FORMS

Öz

Objective: This study aims to develop and validate green analytical methods, specifically UV spectrophotometry, first-order derivative spectrophotometry, and reverse-phase HPLC (RP-HPLC), for determining Alpelisib (ALP) in bulk and pharmaceutical formulations. By comparing the methods using GAPI and AGREE metrics, the study evaluates their environmental friendliness, precision, and applicability.
Material and Method: The UV spectrophotometric and RP-HPLC analyses were conducted using Shimadzu UV 1800 and Agilent 1100 HPLC systems, respectively. The mobile phase for HPLC comprised 0.1% trifluoroacetic acid in water, acetonitrile, and methanol (50:25:25 v/v/v). ALP tablets were prepared and analyzed after dissolution in methanol/water (50:50 v/v) and filtration. Validation was conducted according to ICH guidelines.
Result and Discussion: The developed methods showed high precision, robustness, and sensitivity. UV and HPLC methods were effective in determining ALP in both bulk drug and tablet formulations, with detection limits of 0.078 μg/ml for direct UV spectrophotometry and 14 μg/ml for RP-HPLC. Greenness evaluation highlighted the methods' environmental compatibility, making them suitable for sustainable pharmaceutical analysis.

Anahtar Kelimeler

Alpelisib, anticancer drug, greenness evaluation, RP-HPLC, spectrophotometric, validation

Kaynakça

• 1. Narayan, P., Prowell, T.M., Gao, J.J., Fernandes, L.L., Li, E., Jiang, X., Qiu, J., Fan, J., Song, P., Yu, J. (2021). FDA approval summary: Alpelisib plus fulvestrant for patients with HR-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer. Clinical Cancer Research, 27(7), 1842-1849. [CrossRef]
• 2. Yu, M., Chen, J., Xu, Z., Yang, B., He, Q., Luo, P., Yan, H., Yang, X. (2023). Development and safety of PI3K inhibitors in cancer. Archives of Toxicology, 97(3), 635-650. [CrossRef]
• 3. Dituri, F., Mazzocca, A., Giannelli, G., Antonaci, S. (2011). PI3K functions in cancer progression, anticancer immunity and immune evasion by tumors. Journal of Immunology Research, 2011(1), 947858. [CrossRef]
• 4. Hopkins, B.D., Goncalves, M.D., Cantley, L.C. (2020). Insulin-PI3K signalling: An evolutionarily insulated metabolic driver of cancer. Nature Reviews Endocrinology, 16(5), 276-283. [CrossRef]
• 5. Yuan, T., Cantley, L. (2008). PI3K pathway alterations in cancer: Variations on a theme. Oncogene, 27(41), 5497-5510. [CrossRef]
• 6. Foukas, L.C., Claret, M., Pearce, W., Okkenhaug, K., Meek, S., Peskett, E., Sancho, S., Smith, A.J., Withers, D.J., Vanhaesebroeck, B. (2006). Critical role for the p110α phosphoinositide-3-OH kinase in growth and metabolic regulation. Nature, 441(7091), 366-370. [CrossRef]
• 7. Heavey, S., O’Byrne, K. J., Gately, K. (2014). Strategies for co-targeting the PI3K/AKT/mTOR pathway in NSCLC. Cancer Treatment Reviews, 40(3), 445-456. [CrossRef]
• 8. Aslam, R., Toomey, S., Hennessy, B. (2021). P-287 Preclinical evaluation of alpelisib (PI3K inhibitor) and its synergistic effect in combination with ribociclib (CDK 4/6 inhibitor) in colorectal cancer. Annals of Oncology, 32(3), S194-S195. [CrossRef]
• 9. Konstantinopoulos, P.A., Barry, W.T., Birrer, M., Westin, S.N., Cadoo, K.A., Shapiro, G.I., Mayer, E.L., O'Cearbhaill, R.E., Coleman, R.L., Kochupurakkal, B., Whalen, C., Curtis, J., Farooq, S., Luo, W., Eismann, J., Buss, M. K., Aghajanian, C., Mills, G. B., Palakurthi, S., Kirschmeier, P., Liu, J., Cantley, L.C.C, Kaufmann, P., Swisher, M.E., D’Andrea, D.A., Winer, E., Wulf, M.G., Matulonis, A.U. (2019). Olaparib and α-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: A dose-escalation and dose-expansion phase 1b trial. The Lancet Oncology, 20(4), 570-580. [CrossRef]
• 10. Seo, S.W., Kim, J.M., Han, D.G., Geum, D., Yun, H., Yoon, I.-S. (2021). A sensitive HPLC-FLD method for the quantification of alpelisib, a novel phosphatidylinositol 3-kinase inhibitor, in rat plasma: Drug metabolism and pharmacokinetic evaluation in vitro and in vivo. Journal of Chromatography B, 1163, 122508. [CrossRef]
• 11. Majumder, T., Gubbiyappa, S. K. (2023). Development and validation of LC-MS/MS method for alpelisib quantification in human plasma: Application to pharmacokinetics in healthy rabbits. Journal of Applied Pharmaceutical Science, 13(3), 089-096. [CrossRef]
• 12. Wang, Q., Lan, X., Zhao, Z., Su, X., Zhang, Y., Zhou, X.-Y., Xu, R.-A. (2021). Characterization of Alpelisib in rat plasma by a newly developed UPLC-MS/MS method: Application to a drug-drug interaction study. Frontiers in Pharmacology, 12, 743411. [CrossRef]
• 13. Bouali, W., Erk, N., Genc, A.A., Ahmed, H.E.H., Soylak, M. (2023). A new and powerful electrochemical sensing platform based on MWCNTs@ Fe3O4@ CuAl2O4 for the determination of the anticancer agent Alpelisib in bulk and biological fluids. Microchemical Journal, 195, 109478. [CrossRef]
• 14. Bouali, W., Kurtay, G., Genç, A.A., Erk, N. (2024). Comprehensive analysis of Alpelisib detection: Uniting molecular docking, dynamics, and precision electrochemistry at the PEDOT: PSS-carbon paste interface. Microchemical Journal, 204, 111014. [CrossRef]
• 15. Mohamed, A.R., Abolmagd, E., Badrawy, M., Nour, I.M. (2022). Innovative earth-friendly UV-spectrophotometric technique for in vitro dissolution testing of miconazole nitrate and nystatin in their vaginal suppositories: Greenness assessment. Journal of AOAC International, 105(6), 1528-1535. [CrossRef]
• 16. Elmasry, M.S., Serag, A., Hassan, W.S., El-Mammli, M.Y., Badrawy, M. (2022). Spectrophotometric determination of aspirin and omeprazole in the presence of salicylic acid as a degradation product: A comparative evaluation of different univariate/multivariate post processing algorithms. Journal of AOAC International, 105(1), 309-316. [CrossRef]
• 17. Sankar, R., Snehalatha, K.S., Firdose, S.T., Babu, P.S. (2019). Applications in HPLC in pharmaceutical analysis. International Journal of Pharmaceutical Sciences Review and Research, 59, 117-124.
• 18. Locatelli, M., Melucci, D., Carlucci, G., Locatelli, C. (2012). Recent HPLC strategies to improve sensitivity and selectivity for the analysis of complex matrices. Instrumentation Science & Technology, 40(2-3), 112-137. [CrossRef]
• 19. Sass-Kiss, A. (2008). Chromatographic Technique: High-Performance Liquid Chromatography (HPLC). In: Sun, D.-W. (Ed.), Modern Techniques for Food Authentication, (pp. 361-396). Academic Press: Ireland.
• 20. Rani, P., Nanda, B.P., Paul, P., Chawla, R., Bhatia, R. (2024). Exploring advanced strategies in SPME-HPLC-DAD: Enhancing analytical precision and diverse applications in modern era. Journal of Liquid Chromatography & Related Technologies, 47(6-10), 181-200. [CrossRef]
• 21. Destere, A., Merino, D., Bonesso, L., Lavrut, T., Bernasconni, A., Garraffo, R., Gérard, A. O., Drici, M.D. (2023). A HPLC-DAD method to facilitate large-scale therapeutic drug monitoring of dalbavancin. Journal of Chromatography B, 1222, 123694. [CrossRef]
• 22. Płotka-Wasylka, J. (2018). A new tool for the evaluation of the analytical procedure: Green analytical procedure index. Talanta, 181, 204-209. [CrossRef]
• 23. Nowak, P.M., Wietecha-Posłuszny, R., Pawliszyn, J. (2021). White analytical chemistry: An approach to reconcile the principles of green analytical chemistry and functionality. TrAC Trends in Analytical Chemistry, 138, 116223. [CrossRef]