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
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.
Details
| Primary Language | English |
|---|---|
| Subjects | Pharmaceutical Analytical Chemistry, Pharmaceutical Chemistry |
| Journal Section | Research Article |
| Authors | |
| Publication Date | October 23, 2024 |
| Submission Date | November 23, 2023 |
| Acceptance Date | July 29, 2024 |
| Published in Issue | Year 2024 |