The Stability-Indicating Ultra High-Performance Liquid Chromatography with Diode Array Detector and Tandem Mass Spectrometry Method Applied for the Forced Degradation Study of Ritlecitinib: An Appraisal of Green and Blue Metrics
Background/Objectives: Janus kinase inhibitors open new horizons for small-molecule drugs in treating inflammatory bowel disease, with ritlecitinib demonstrating significant efficacy in clinical trials for ulcerative colitis and Crohn’s disease. Ritlecitinib, a second-generation JAK3 inhibitor, is a...
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2025-01-01
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| author | Jelena Kovačić Daniela Amidžić Klarić Nikša Turk Željko Krznarić Emma Riordan Ana Mornar |
| author_facet | Jelena Kovačić Daniela Amidžić Klarić Nikša Turk Željko Krznarić Emma Riordan Ana Mornar |
| author_sort | Jelena Kovačić |
| collection | DOAJ |
| description | Background/Objectives: Janus kinase inhibitors open new horizons for small-molecule drugs in treating inflammatory bowel disease, with ritlecitinib demonstrating significant efficacy in clinical trials for ulcerative colitis and Crohn’s disease. Ritlecitinib, a second-generation JAK3 inhibitor, is a novel therapeutic agent for alopecia areata and other autoimmune conditions. Methods: A new stability-indicating UHPLC-DAD-MS/MS method was developed, validated, and applied for a forced degradation study of ritlecitinib under ICH guidelines. Results: The method demonstrated high specificity, sensitivity (LOD: 0.04 µg/mL; LOQ: 0.14 µg/mL), precision (RSD ≤ 0.15%), and accuracy (99.9–100.3%). Forced degradation studies under acidic, basic, oxidative, thermal, and photolytic conditions revealed four novel degradation products. Basic degradation followed second-order kinetics, while oxidative degradation followed zero-order kinetics. Conclusions: The validated method reliably characterized ritlecitinib’s stability and degradation products, providing essential data for optimizing formulation, determining proper storage conditions, anticipating drug–excipient interactions, and ensuring quality control. The eco-friendliness and applicability of the developed forced degradation procedure were evaluated using various green and blue metric tools. Incorporating green analytical principles underscores its potential for sustainable pharmaceutical analysis. |
| format | Article |
| id | doaj-art-2415868826a34fda91af36fa7927b0ca |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj-art-2415868826a34fda91af36fa7927b0ca2025-01-24T13:45:28ZengMDPI AGPharmaceuticals1424-82472025-01-0118112410.3390/ph18010124The Stability-Indicating Ultra High-Performance Liquid Chromatography with Diode Array Detector and Tandem Mass Spectrometry Method Applied for the Forced Degradation Study of Ritlecitinib: An Appraisal of Green and Blue MetricsJelena Kovačić0Daniela Amidžić Klarić1Nikša Turk2Željko Krznarić3Emma Riordan4Ana Mornar5Department of Pharmaceutical Analysis, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Pharmaceutical Analysis, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Gastroenterology, University Hospital Centre, 10000 Zagreb, CroatiaDepartment of Gastroenterology, University Hospital Centre, 10000 Zagreb, CroatiaSchool of Pharmacy, University College Cork, T12 YT20 Cork, IrelandDepartment of Pharmaceutical Analysis, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, CroatiaBackground/Objectives: Janus kinase inhibitors open new horizons for small-molecule drugs in treating inflammatory bowel disease, with ritlecitinib demonstrating significant efficacy in clinical trials for ulcerative colitis and Crohn’s disease. Ritlecitinib, a second-generation JAK3 inhibitor, is a novel therapeutic agent for alopecia areata and other autoimmune conditions. Methods: A new stability-indicating UHPLC-DAD-MS/MS method was developed, validated, and applied for a forced degradation study of ritlecitinib under ICH guidelines. Results: The method demonstrated high specificity, sensitivity (LOD: 0.04 µg/mL; LOQ: 0.14 µg/mL), precision (RSD ≤ 0.15%), and accuracy (99.9–100.3%). Forced degradation studies under acidic, basic, oxidative, thermal, and photolytic conditions revealed four novel degradation products. Basic degradation followed second-order kinetics, while oxidative degradation followed zero-order kinetics. Conclusions: The validated method reliably characterized ritlecitinib’s stability and degradation products, providing essential data for optimizing formulation, determining proper storage conditions, anticipating drug–excipient interactions, and ensuring quality control. The eco-friendliness and applicability of the developed forced degradation procedure were evaluated using various green and blue metric tools. Incorporating green analytical principles underscores its potential for sustainable pharmaceutical analysis.https://www.mdpi.com/1424-8247/18/1/124ritlecitinibJAK3 inhibitorstability-indicating methodforced degradation studygreen analytical chemistrydegradation kinetics |
| spellingShingle | Jelena Kovačić Daniela Amidžić Klarić Nikša Turk Željko Krznarić Emma Riordan Ana Mornar The Stability-Indicating Ultra High-Performance Liquid Chromatography with Diode Array Detector and Tandem Mass Spectrometry Method Applied for the Forced Degradation Study of Ritlecitinib: An Appraisal of Green and Blue Metrics Pharmaceuticals ritlecitinib JAK3 inhibitor stability-indicating method forced degradation study green analytical chemistry degradation kinetics |
| title | The Stability-Indicating Ultra High-Performance Liquid Chromatography with Diode Array Detector and Tandem Mass Spectrometry Method Applied for the Forced Degradation Study of Ritlecitinib: An Appraisal of Green and Blue Metrics |
| title_full | The Stability-Indicating Ultra High-Performance Liquid Chromatography with Diode Array Detector and Tandem Mass Spectrometry Method Applied for the Forced Degradation Study of Ritlecitinib: An Appraisal of Green and Blue Metrics |
| title_fullStr | The Stability-Indicating Ultra High-Performance Liquid Chromatography with Diode Array Detector and Tandem Mass Spectrometry Method Applied for the Forced Degradation Study of Ritlecitinib: An Appraisal of Green and Blue Metrics |
| title_full_unstemmed | The Stability-Indicating Ultra High-Performance Liquid Chromatography with Diode Array Detector and Tandem Mass Spectrometry Method Applied for the Forced Degradation Study of Ritlecitinib: An Appraisal of Green and Blue Metrics |
| title_short | The Stability-Indicating Ultra High-Performance Liquid Chromatography with Diode Array Detector and Tandem Mass Spectrometry Method Applied for the Forced Degradation Study of Ritlecitinib: An Appraisal of Green and Blue Metrics |
| title_sort | stability indicating ultra high performance liquid chromatography with diode array detector and tandem mass spectrometry method applied for the forced degradation study of ritlecitinib an appraisal of green and blue metrics |
| topic | ritlecitinib JAK3 inhibitor stability-indicating method forced degradation study green analytical chemistry degradation kinetics |
| url | https://www.mdpi.com/1424-8247/18/1/124 |
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