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Chromatographic profiling of leniolisib impurities using HPLC and LC-MS/MS: degradation behaviour, structural characterization, and in-silico toxicity evaluation

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Titel: Chromatographic profiling of leniolisib impurities using HPLC and LC-MS/MS: degradation behaviour, structural characterization, and in-silico toxicity evaluation
Autoren: Gunupati, Rahul, Tulasi, S. Lakshmi, Shaik, Rasheed Babu, Lakshmi, L. Bhagya, Tangeti, Venkata Swamy
Quelle: Journal of Applied Pharmaceutical Research; Vol. 13 No. 4 (2025); 112-123
Verlagsinformationen: Creative Pharma Assent, 2025.
Publikationsjahr: 2025
Schlagwörter: stress degradation compounds, LC–MS/MS characterization, Leniolisib, impurities analysis, in-silico study
Beschreibung: Background: This study presents a comprehensive analytical investigation of leniolisib, focusing on impurity profiling, degradation kinetics, structural characterization, and in silico toxicity prediction of degradation products (DPs). Methodology: A systematic approach was employed to optimize the analytical method for leniolisib and its impurities, along with LC–MS/MS-based identification and in-silico toxicity prediction of DPs. Result and Discussion: Method optimized as Waters Symmetry C18 column and an isocratic mobile phase (methanol: sodium acetate buffer, 55:45 v/v) at 0.90 mL/min with UV detection at 229 nm. Leniolisib was most susceptible to acid and oxidative stress, resulting in 31.24% and 39.58% degradation, respectively. Pseudo-first-order kinetics was observed with rate constants of 0.0329 h⁻¹ (acidic) and 0.0414 h⁻¹ (oxidative), with half life of 21.08 h and 16.73 h. LC–MS/MS elucidates the identities of major DPs that enable the proposed degradation pathways. The MS/MS characterization confirms DP 1 with a formula of C13H15N5O with a mass of 257 g/mol, whereas DP 2, 3, and 4 were identified to have formulas of C20H26N6O2, C13H12F3N5O, and C17H19F3N6O with masses of 382, 311, and 380 g/mol, respectively. The In-silico toxicity predictions show DP 1 (LD₅₀ = 500 mg/kg) and DP 2 (729 mg/kg) as moderate toxicity (class 4), DP 4 shows the least toxicity (class 5, LD₅₀ = 1750 mg/kg), whereas DP3 shows the highest toxicity (class 3, LD₅₀ = 250 mg/kg). Conclusion: The developed method and accompanying data provide a critical foundation for routine quality control, stability testing, and regulatory submissions for leniolisib-based formulations.
Publikationsart: Article
Dateibeschreibung: application/pdf
ISSN: 2348-0335
DOI: 10.69857/joapr.v13i4.1143
Zugangs-URL: https://www.japtronline.com/index.php/joapr/article/view/1143
Rights: CC BY NC
Dokumentencode: edsair.doi.dedup.....e5ca975a5b6740fd9d69eb9d6d4ae533
Datenbank: OpenAIRE
Beschreibung
Abstract:Background: This study presents a comprehensive analytical investigation of leniolisib, focusing on impurity profiling, degradation kinetics, structural characterization, and in silico toxicity prediction of degradation products (DPs). Methodology: A systematic approach was employed to optimize the analytical method for leniolisib and its impurities, along with LC–MS/MS-based identification and in-silico toxicity prediction of DPs. Result and Discussion: Method optimized as Waters Symmetry C18 column and an isocratic mobile phase (methanol: sodium acetate buffer, 55:45 v/v) at 0.90 mL/min with UV detection at 229 nm. Leniolisib was most susceptible to acid and oxidative stress, resulting in 31.24% and 39.58% degradation, respectively. Pseudo-first-order kinetics was observed with rate constants of 0.0329 h⁻¹ (acidic) and 0.0414 h⁻¹ (oxidative), with half life of 21.08 h and 16.73 h. LC–MS/MS elucidates the identities of major DPs that enable the proposed degradation pathways. The MS/MS characterization confirms DP 1 with a formula of C13H15N5O with a mass of 257 g/mol, whereas DP 2, 3, and 4 were identified to have formulas of C20H26N6O2, C13H12F3N5O, and C17H19F3N6O with masses of 382, 311, and 380 g/mol, respectively. The In-silico toxicity predictions show DP 1 (LD₅₀ = 500 mg/kg) and DP 2 (729 mg/kg) as moderate toxicity (class 4), DP 4 shows the least toxicity (class 5, LD₅₀ = 1750 mg/kg), whereas DP3 shows the highest toxicity (class 3, LD₅₀ = 250 mg/kg). Conclusion: The developed method and accompanying data provide a critical foundation for routine quality control, stability testing, and regulatory submissions for leniolisib-based formulations.
ISSN:23480335
DOI:10.69857/joapr.v13i4.1143