{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T06:53:34Z","timestamp":1781765614097,"version":"3.54.5"},"reference-count":25,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>This study presents the development and validation of three selective chromatographic methods for the identification and quantification of related substances, including process\u2010related impurities and degradation products, in combined ophthalmic formulations of dorzolamide hydrochloride (DH) and timolol maleate (TM). The methods were applied to ophthalmic solutions containing 2.0% DH and 0.5% TM (20 and 5\u2009mg\/mL, respectively) and were designed to comply with the requirements of the USP, B.P., and Ph. Eur. Both an in\u2010house developed generic formulation and the reference listed drug formulations, COSOPT PF and COSOPT, were evaluated during method development and validation. The novelty of this work lies in the use of three complementary chromatographic approaches that significantly improve specificity, selectivity, and impurity profiling in complex ophthalmic matrices during the aqueous in\u2010process of both phases (aqueous and polymer mixing phase). In addition, the study provides a comparative assessment between preservative\u2010free and preserved formulations, supporting regulatory compliance, stability evaluation, and bioequivalence assessment of generic ophthalmic products.<\/jats:p>","DOI":"10.1002\/bmc.70522","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T02:36:17Z","timestamp":1781490977000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive Analytical Method Development for Related Substance Determination in Dorzolamide Hydrochloride\u2013Timolol Maleate Ophthalmic Solutions: Multi\u2010Method Approach and Regulatory Compliance"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4158-1764","authenticated-orcid":false,"given":"Ramakrishna","family":"Kapavarapu","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Sciences &amp; Research Bhagwant University  Ajmer Rajasthan India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1385-1877","authenticated-orcid":false,"given":"Srujan Kumar","family":"Mantena","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences &amp; Research Bhagwant University  Ajmer Rajasthan India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12249\u2010009\u20109268\u20104"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/03639041003801885"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5681"},{"issue":"8","key":"e_1_2_9_5_1","first-page":"745","article-title":"Analytical Quality by Design Approach for Chromatographic Method Development and Impurity Profiling","volume":"61","author":"Bisen P. S.","year":"2023","journal-title":"Journal of Chromatographic Science"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/separations11030083"},{"issue":"2","key":"e_1_2_9_7_1","article-title":"Stability\u2010Indicating Chromatographic Methods for the Determination of Ophthalmic Drug Products and Related Impurities","volume":"38","author":"El Deeb S.","year":"2024","journal-title":"Biomedical Chromatography"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12249\u2010009\u20109238\u2010x"},{"key":"e_1_2_9_9_1","unstructured":"International Council for Harmonisation (ICH).2023. \u201cICH Q2(R2): Validation of Analytical Procedures.\u201d International Council for Harmonisation (ICH)."},{"key":"e_1_2_9_10_1","unstructured":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).1996. \u201cStability Testing: Photostability Testing of New Drug Substances and Products Q1B.\u201d ICH."},{"key":"e_1_2_9_11_1","first-page":"11","article-title":"Forced Degradation Studies and Development of Stability\u2010Indicating Analytical Methods: A Review","volume":"86","author":"Jadhav M. L.","year":"2017","journal-title":"Journal of Pharmaceutical and Biomedical Analysis"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/scipharm85030025"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13010200"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00417\u2010010\u20101383\u20100"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13065\u2010022\u201000819\u20109"},{"issue":"4","key":"e_1_2_9_16_1","article-title":"Recent Advances in Impurity Profiling and Stability\u2010Indicating Methods for Ophthalmic Formulations","volume":"38","author":"Mehta P.","year":"2024","journal-title":"Biomedical Chromatography"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201022998\u20100"},{"issue":"5","key":"e_1_2_9_18_1","first-page":"611","article-title":"Development and Validation of RP\u2010HPLC Methods for Impurity Profiling in Ophthalmic Formulations","volume":"12","author":"Muchakayala S.","year":"2022","journal-title":"Journal of Pharmaceutical Analysis"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.121.4.453"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.123.9.1177"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11671\u2010024\u201004154\u2010x"},{"issue":"1","key":"e_1_2_9_22_1","first-page":"101","article-title":"RP\u2010HPLC Method Development and Validation for Simultaneous Estimation of Ophthalmic Drug Combinations","volume":"16","author":"Ramakrishna K.","year":"2025","journal-title":"International Journal of Pharmaceutical Sciences and Research"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1088\/1748\u2010605X\/adb555"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1089\/jop.1996.12.363"},{"issue":"3","key":"e_1_2_9_25_1","first-page":"215","article-title":"Regulatory Perspectives and Forced Degradation Strategies in Pharmaceutical Analysis","volume":"18","author":"Vankalapati S.","year":"2022","journal-title":"Current Pharmaceutical Analysis"},{"key":"e_1_2_9_26_1","unstructured":"World Health Organization (WHO).2018. \u201cWHO Guidelines on Stability Testing of Active Pharmaceutical Ingredients and Finished Pharmaceutical Products.\u201d WHO Technical Report Series No. 1010 Annex 10 WHO."}],"container-title":["Biomedical Chromatography"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.70522","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bmc.70522","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.70522","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T06:22:12Z","timestamp":1781763732000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bmc.70522"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,14]]},"references-count":25,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/bmc.70522"],"URL":"https:\/\/doi.org\/10.1002\/bmc.70522","archive":["Portico"],"relation":{},"ISSN":["0269-3879","1099-0801"],"issn-type":[{"value":"0269-3879","type":"print"},{"value":"1099-0801","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,14]]},"assertion":[{"value":"2026-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70522"}}