Research Article
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Year 2024, Volume: 49 Issue: 3, 449 - 464, 23.10.2024
https://doi.org/10.55262/fabadeczacilik.1394869

Abstract

References

  • Wirth, L. J., Sherman, E., Robinson, B., Solomon, B., Kang, H., Lorch, J., ... et al. (2020). Efficacy of selpercatinib in RET-altered thyroid cancers. N Engl J Med, 383, 825-835.

Evaluation of the Genotoxic Impurities of Selpercatinib Through HPLC and LCMS/MS Identification of Selpercatinib Stress Degradation Products

Year 2024, Volume: 49 Issue: 3, 449 - 464, 23.10.2024
https://doi.org/10.55262/fabadeczacilik.1394869

Abstract

The current investigation entails the characterization of seven degradation products (DPs) formed in different stress conditions of selpercatinib employing liquid chromatography–tandem mass spectrometry (LCMS/MS). Additionally, high-performance liquid chromatographic (HPLC) method for precise quantifying genotoxic impurities of selpercatinib. To explore the stability profile of selpercatinib, it was subjected to forced degradation experiments including acidic, basic, oxidative, photolytic, and thermal stress were conducted. These experiments revealed the degradation of selpercatinib under basic, acidic and photolytic conditions, resulting in the formation of seven distinct DPs. The chromatographic resolution of selpercatinib and its impurities along with DPs was effectively attained on Zorbax C18 (250 mm × 4.6 mm, 5 μm) column using aqueous ammonium acetate and methanol in 70:30 (v/v) at pH 4.5 with 0.1% formic acid as mobile phase, pumped isocratically at 0.9 mL/min and 226 nm wavelength. The approach generates a precise calibration curve that accurately fits within 15-120 μg/mL range for selpercatinib and LOQ (0.015 μg/mL) to 0.12 μg/mL for impurities with acceptable precision, accuracy and recovery. The efficacy of this method was validated through LCMS/MS, which allowed for the verification of the chemical structures of newly generated degradation products of selpercatinib. Hence this approach can appropriate for resolution and quantification of genotoxic impurities of selpercatinib and can also applicable for evaluation stress degradation products.

Ethical Statement

No animal involved to carry out this research work Hence, no Ethical approval required Please accept the submission

References

  • Wirth, L. J., Sherman, E., Robinson, B., Solomon, B., Kang, H., Lorch, J., ... et al. (2020). Efficacy of selpercatinib in RET-altered thyroid cancers. N Engl J Med, 383, 825-835.
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Details

Primary Language English
Subjects Pharmaceutical Analytical Chemistry, Pharmaceutical Chemistry
Journal Section Research Article
Authors

Divya Bheemireddy 0009-0007-7444-1422

Murali Prakash J This is me 0009-0000-5376-6649

Venkata Chiranjeevi Eevana This is me 0009-0004-0609-0198

Bhaskara Rao Tadıboına This is me 0000-0002-0632-4159

Publication Date October 23, 2024
Submission Date November 23, 2023
Acceptance Date July 29, 2024
Published in Issue Year 2024 Volume: 49 Issue: 3

Cite

APA Bheemireddy, D., J, M. P., Eevana, V. C., Tadıboına, B. R. (2024). Evaluation of the Genotoxic Impurities of Selpercatinib Through HPLC and LCMS/MS Identification of Selpercatinib Stress Degradation Products. Fabad Journal of Pharmaceutical Sciences, 49(3), 449-464. https://doi.org/10.55262/fabadeczacilik.1394869