{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:13:11Z","timestamp":1778850791119,"version":"3.51.4"},"reference-count":58,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemistryOpen"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:p>This study presents a sustainable chromatographic method for the analysis of diltiazem. Retention behavior and the effect of mobile phase pH were investigated to determine the dissociation constant. Chromatographic experiments were performed at 37\u00b0C on a Gemini NX C18 column in binary mixtures of ethanol\u2010water containing 40%, 45%, and 50% (v\/v) ethanol and methanol\u2010water containing 45%, 50%, and 55% (v\/v) methanol. Using these retention data, the  value of diltiazem, which has low solubility in water, was calculated. Beyond analytical performance, the sustainability of method was evaluated multimetrically approach using the Environmental, Performance, and Practicality Index, the Carbon Footprint Reduction Index, and the Sustainability of Analytical Methods Index. This complementary framework provides a holistic assessment of operational greenness, carbon intensity, and global sustainability goals in accordance with the latest guidelines. The method for diltiazem determination according to these tools showed linearity with a correlation coefficient of 0.999 in the concentration range of 1.0\u201315\u2009\u00b5g\/mL and achieved acceptable precision and accuracy. Validated according to ICH Q2(R2) guidelines, the procedure was successfully applied to tablet formulations and forced degradation studies. This work establishes a comprehensive, ecofriendly methodological approach suitable for pharmaceutical analysis.<\/jats:p>","DOI":"10.1002\/open.70215","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T05:06:49Z","timestamp":1776748009000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sustainable Ethanol\u2010Based Reversed\u2010Phase Liquid Chromatography for Determination of Diltiazem pKa and Quantification with Integrated Green and White Analytical Metrics"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7061-6279","authenticated-orcid":false,"given":"Zehra","family":"\u00dcst\u00fcn","sequence":"first","affiliation":[{"name":"Atayalvac Vocational School of Health Services Suleyman Demirel University  Isparta Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0130lkay","family":"Kon\u00e7e","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Suleyman Demirel University  Isparta Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebru","family":"\u00c7ubuk Demiralay","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Suleyman Demirel University  Isparta Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5CE01204J"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2021.120790"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/0126667312325351241009063848"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/openhrt-2022-002179"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24108472"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1134658"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/0470087951"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470688427"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2025.116671"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.4137\/ACI.S12304"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2025.116019"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5482"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202402900"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23051065"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molliq.2023.123306"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781118592014"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9673(99)00915-2"},{"key":"e_1_2_10_19_1","volume-title":"Chromatography Today","author":"Poole C. F.","year":"1991"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9673(93)80506-4"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2025.104005"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.greeac.2025.100306"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13065-025-01486-2"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scp.2025.102294"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2025.114781"},{"key":"e_1_2_10_26_1","volume-title":"ICH Harmonised Guideline: Q2(R2) \u2013 Validation of Analytical Procedures","author":"International Council for Harmonisation (ICH)","year":"2023"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/chromsci\/bmu173"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2026.117560"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12247-026-10498-x"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.202300346"},{"key":"e_1_2_10_31_1","first-page":"461427","article-title":"Determination of Physicochemical Properties of Small Molecules by Reversed\u2010Phase Liquid Chromatography","volume":"2020","author":"Poole C. F.","year":"1626","journal-title":"Journal of Chromatography A"},{"key":"e_1_2_10_32_1","first-page":"51050","article-title":"Determination of Retention Behavior and pKa Values of Some Phenothiazines with Green Chemistry Approach","volume":"10","author":"\u00d6zt\u00fcrk Z.","year":"2025","journal-title":"ACS Omega"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9673(02)01444-9"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molliq.2020.113930"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:JOSL.0000037772.55748.a3"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9673(00)01271-1"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01210a043"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.5541\/ijot.1017174"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4612-4974-0_24"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5GC00615E"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rechem.2026.103048"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1134\/S1061934825700327"},{"key":"e_1_2_10_43_1","first-page":"1015","volume-title":"Analytical Instrumentation Handbook","author":"Wells M.","year":"2004"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/chrsci\/49.10.774"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43094-025-00852-0"},{"key":"e_1_2_10_46_1","first-page":"78","article-title":"Analytical Method Development and Validation for the Estimation of Diltiazem Hydrochloride in Bulk and Pharmaceutical Dosage Form by RP\u2010HPLC","volume":"14","author":"Patil B. R.","year":"2024","journal-title":"Journal of Drug Delivery and Therapeutics"},{"key":"e_1_2_10_47_1","first-page":"580","article-title":"A Validated RP\u2010HPLC Method for the Determination of Diltiazem in Raw Material and Pharmaceutical Dosage Form","volume":"4","author":"Kumar B. M. S.","year":"2013","journal-title":"International Journal of Pharmacy and Biological Sciences"},{"key":"e_1_2_10_48_1","first-page":"1528","article-title":"Method Development, Validation and Stability Study of Diltiazem by RP\u2010HPLC Method","volume":"8","author":"Dash H.","year":"2014","journal-title":"Journal of Pharmaceutical Research"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2024.116324"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1080\/28378083.2024.2375114"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00769-025-01661-x"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/353814"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/sscp.202400155"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac00070a013"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1351\/pac199870071419"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1351\/pac198759111549"},{"key":"e_1_2_10_57_1","volume-title":"NLREG Version 4.0 [software]","author":"Sherrod P. H.","year":"1991"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules30173573"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0921-3449(01)00119-7"}],"container-title":["ChemistryOpen"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/open.70215","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/open.70215","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/open.70215","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:02:28Z","timestamp":1778850148000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/open.70215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":58,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/open.70215"],"URL":"https:\/\/doi.org\/10.1002\/open.70215","archive":["Portico"],"relation":{},"ISSN":["2191-1363","2191-1363"],"issn-type":[{"value":"2191-1363","type":"print"},{"value":"2191-1363","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]},"assertion":[{"value":"2026-03-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70215"}}