{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:43:50Z","timestamp":1790790230703,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Electrophoresis"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Siponimod fumarate (SIP), a potent selective S1P receptor modulator, has emerged as a critical therapeutic agent in the treatment of multiple sclerosis. Recognizing the increasing regulatory demands for robust impurity profiling and method reliability, this study reports the development and optimization of an HPLC method for the simultaneous determination of SIP and its related impurities in both bulk drug substance and tablet dosage forms. The method was developed within an Analytical Quality by Design (AQbD) framework, guided by ICH Q14 principles, ensuring a systematic and risk\u2010based approach throughout the analytical lifecycle. Chromatographic separation necessary for resolving critical impurities was achieved on an XSelect HSS T3 column (150\u00a0mm\u00a0\u00d7\u00a04.6\u00a0mm, 3.5\u00a0\u00b5m) using a stepped gradient elution program with 0.1% perchloric acid in water and acetonitrile as the mobile phases. Optimal separation conditions, identified through the AQbD process to meet stringent performance criteria, were determined at a column temperature of 42.5\u00b0C, a flow rate of 1.4\u00a0mL\u00a0min\n                    <jats:sup>\u22121<\/jats:sup>\n                    , and UV detection at 212\u00a0nm. The method performance was rigorously evaluated through accuracy profiles, confirming both its precision and trueness across the targeted concentration range. In parallel, as part of a holistic method characterization, environmental sustainability was assessed using comprehensive greenness metrics, whereas its practical applicability was further substantiated using the Blue Applicability Grade Index (BAGI) and the Red\u2013Green\u2013Blue 12 (RGB12) algorithms. This approach not only bridges the gap created by the absence of an official pharmacopoeial monograph for SIP but also offers a robust, well\u2010characterized, and sustainable platform for pharmaceutical quality control, aligning method development with both regulatory performance needs and environmental awareness.\n                  <\/jats:p>","DOI":"10.1002\/elps.70039","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T06:36:02Z","timestamp":1758695762000},"page":"1661-1672","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["An ICH Q14\u2010Guided AQbD Framework for the Development of an HPLC Method: Analysis of Siponimod Fumarate and Its Impurities"],"prefix":"10.1002","volume":"46","author":[{"given":"Afnan","family":"Altwala","sequence":"first","affiliation":[{"name":"Department of Chemistry College of Science Al\u2010Zulfi Majmaah University  Al Majma'ah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman M.","family":"Algohary","sequence":"additional","affiliation":[{"name":"Department of Chemistry College of Science Al\u2010Zulfi Majmaah University  Al Majma'ah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona H.","family":"Alhalafi","sequence":"additional","affiliation":[{"name":"Department of Chemistry College of Science Al\u2010Zulfi Majmaah University  Al Majma'ah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa M.","family":"Eraqi","sequence":"additional","affiliation":[{"name":"Department of Biology College of Science Al\u2010Zulfi Majmaah University  Al Majma'ah Saudi Arabia"},{"name":"Microbiology and Immunology Department Veterinary Research Institute National Research Centre  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Egyptian Drug Authority (EDA)  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2024.100977"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-022-00939-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12247-021-09607-9"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scp.2024.101788"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2024.111535"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2018.09.023"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemolab.2025.105389"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2019.01.007"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scp.2024.101743"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scp.2023.101339"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/10826076.2019.1626742"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cem.70023"},{"key":"e_1_2_8_14_1","unstructured":"United States Pharmacopeia. <1210>Statistical Tools for Procedure Validation. 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