{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T21:01:07Z","timestamp":1784062867467,"version":"3.55.0"},"reference-count":38,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T00:00:00Z","timestamp":1607644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Project Based Mevlana Exchange Program","award":["MEV-2018-1295"],"award-info":[{"award-number":["MEV-2018-1295"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In a recent study, opposite enantiomer elution order was observed for ketoprofen enantiomers on two amylose-phenylcarbamate-based chiral columns with the same chemical composition of the chiral selector but in one case with coated while in the other with an immobilized chiral selector. In the present study, the influence of this uncommon effect on method validation parameters for the determination of minor enantiomeric impurity in dexketoprofen was studied. The validated methods with two alternative elution orders for enantiomers were applied for the evaluation of enantiomeric impurity in six marketed dexketoprofen formulations from various vendors. In most of these formulations except one the content of enantiomeric impurity exceeded 0.1% (w\/w).<\/jats:p>","DOI":"10.3390\/molecules25245865","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:45:36Z","timestamp":1607906736000},"page":"5865","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Effect of Enantiomer Elution Order on the Determination of Minor Enantiomeric Impurity in Ketoprofen and Enantiomeric Purity Evaluation of Commercially Available Dexketoprofen Formulations"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9353-8867","authenticated-orcid":false,"given":"Kenan Can","family":"Tok","sequence":"first","affiliation":[{"name":"Department of Forensic Toxicology, Institute of Forensic Sciences, Ankara University, Ankara 06590, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2793-7154","authenticated-orcid":false,"given":"Mehmet","family":"Gumustas","sequence":"additional","affiliation":[{"name":"Department of Forensic Toxicology, Institute of Forensic Sciences, Ankara University, Ankara 06590, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgi","family":"Jibuti","sequence":"additional","affiliation":[{"name":"Institute of Physical and Analytical Chemistry, School of Exact and Natural Sciences, Tbilisi State University, Chavchavadze Ave 3, 0179 Tbilisi, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halit Sinan","family":"Suzen","sequence":"additional","affiliation":[{"name":"Department of Forensic Toxicology, Institute of Forensic Sciences, Ankara University, Ankara 06590, Turkey"},{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Ankara University, Ankara 06560, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7494-3077","authenticated-orcid":false,"given":"Sibel A.","family":"Ozkan","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy, Ankara University, Ankara 06560, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bezhan","family":"Chankvetadze","sequence":"additional","affiliation":[{"name":"Institute of Physical and Analytical Chemistry, School of Exact and Natural Sciences, Tbilisi State University, Chavchavadze Ave 3, 0179 Tbilisi, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.chroma.2019.05.026","article-title":"Chromatographic and thermodynamic comparison of amylose tris(3-chloro-5-methylphenylcarbamate) coated or covalently immobilized on silica in high-performance liquid chromatographic separation of the enantiomers of select chiral weak acids","volume":"1602","author":"Maisuradze","year":"2019","journal-title":"J. Chromatogr. A"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/toxsci\/kfp097","article-title":"Chiral toxicology: It\u2019s the same thing...only different","volume":"110","author":"Smith","year":"2009","journal-title":"Toxicol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1093\/jat\/bkx074","article-title":"Chiral resolution and enantioselectivity of synthetic cathinones: A Brief Review","volume":"42","author":"Silva","year":"2018","journal-title":"J. Anal. Toxicol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1080\/17460441.2017.1383981","article-title":"Approaches for multi-gram scale isolation of enantiomers for drug discovery","volume":"12","author":"Rossi","year":"2017","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.drudis.2016.09.018","article-title":"Strategy for large-scale isolation of enantiomers in drug discovery","volume":"22","author":"Leek","year":"2017","journal-title":"Drug. Discov. Today"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2734","DOI":"10.1021\/cr040700c","article-title":"Asymmetric synthesis of active pharmaceutical ingredients","volume":"106","author":"Farina","year":"2006","journal-title":"Chem. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1039\/C2CS35410A","article-title":"Rhodium-catalysed asymmetric hydrogenation as a valuable synthetic tool for the preparation of chiral drugs","volume":"42","author":"Etayo","year":"2013","journal-title":"Chem. Soc. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4152","DOI":"10.2174\/0929867325666180129094955","article-title":"Analytical and preparative scale separation of enantiomers of chiral drugs by chromatography and related methods","volume":"25","author":"Gumustas","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1021\/acs.chemrev.5b00317","article-title":"Efficient separation of enantiomers using stereoregular chiral polymers","volume":"116","author":"Shen","year":"2016","journal-title":"Chem. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"115709","DOI":"10.1016\/j.trac.2019.115709","article-title":"Recent trends in preparation, investigation and application of polysaccharide-based chiral stationary phases for separation of enantiomers in high-performance liquid chromatography","volume":"122","author":"Chankvetadze","year":"2020","journal-title":"Trac. Trends Anal. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.jpba.2017.07.008","article-title":"The market of chiral drugs: Chiral switches versus de novo enantiomerically pure compounds","volume":"147","author":"Calcaterra","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_12","first-page":"70","article-title":"Stereochemistry in Drug Action","volume":"5","author":"Conathy","year":"2003","journal-title":"Prim. Care Companion J. Clin. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/S0140-6736(00)02047-X","article-title":"Chiral switches","volume":"355","author":"Tucker","year":"2000","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0021-9673(01)94410-3","article-title":"Eluting trace components before major constituents: I. Sensitivity enhancement in analytical determinations of optical purity","volume":"389","author":"Perry","year":"1987","journal-title":"J. Chromatogr. A"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/0731-7085(91)80160-B","article-title":"Chiral drugs: An industrial analytical perspective","volume":"9","author":"Wozniak","year":"1991","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.chroma.2004.11.001","article-title":"A new application of stopped-flow chiral HPLC: Inversion of enantiomer elution order","volume":"1061","author":"Cirilli","year":"2004","journal-title":"J. Chromatogr. A"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1002\/jssc.201100339","article-title":"Determination of enantiomeric purity of S-amlodipine by chiral LC with emphasis on reversal of enantiomer elution order","volume":"34","author":"Dossou","year":"2011","journal-title":"J. Sep. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3964","DOI":"10.1021\/ja00403a076","article-title":"A widely useful chiral stationary phase for the high-performance liquid chromatography separation of enantiomers","volume":"103","author":"Pirkle","year":"1981","journal-title":"J. Am. Chem. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jpba.2018.06.045","article-title":"Liquid chromatographic enantiomer separations applying chiral ion-exchangers based on Cinchona alkaloids","volume":"159","author":"Ilisz","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/chromsci\/22.9.411","article-title":"Cyclodextrin bonded phases for the liquid chromatographic separation of optical, geometrical, and structural isomers","volume":"22","author":"Armstrong","year":"1984","journal-title":"J. Chromatogr. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1021\/ac00081a019","article-title":"Macrocyclic antibiotics as a new class of chiral selectors for liquid chromatography","volume":"66","author":"Armstrong","year":"1994","journal-title":"Anal. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0021-9673(00)00504-5","article-title":"Protein-based chiral stationary phases for high-performance liquid chromatography enantioseparations","volume":"906","author":"Haginaka","year":"2001","journal-title":"J. Chromatogr. A"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/jssc.201200885","article-title":"HPLC separation of enantiomers of chiral arylpropionic acid derivatives using polysaccharide-based chiral columns and normal-phase eluents with emphasis on elution order","volume":"36","author":"Matarashvili","year":"2013","journal-title":"J. Sep. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.chroma.2016.08.011","article-title":"Separation and elution order of the enantiomers of some beta-agonists using polysaccharide-based chiral columns and normal phase eluents by high-performance liquid chromatography","volume":"1467","author":"Gumustas","year":"2016","journal-title":"J. Chromatogr. A"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1002\/jssc.201200443","article-title":"HPLC separation of dihydropyridine derivatives enantiomers with emphasis on elution order using polysaccharide-based chiral columns","volume":"35","author":"Jibuti","year":"2012","journal-title":"J. Sep. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0021-9673(94)85121-2","article-title":"Stereoselective effects in the separation of enantiomers of omeprazole and other substituted benzimidazoles on different chiral stationary phases","volume":"660","author":"Persson","year":"1994","journal-title":"J. Chromatogr. A"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/0021-9673(92)85104-2","article-title":"Reversed retention order and other stereoselective effects in the separation of amino alcohols on Chiralcel OD","volume":"592","author":"Persson","year":"1992","journal-title":"J. Chromatogr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.chroma.2016.12.064","article-title":"Separation of enantiomers of chiral weak acids with polysaccharide-based chiral columns and aqueous-organic mobile phases in high-performance liquid chromatography: Typical reversed-phase behavior?","volume":"1483","author":"Matarashvili","year":"2017","journal-title":"J. Chromatogr. A"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.jpba.2007.03.009","article-title":"Reversal of elution order for profen acid enantiomers in normal phase LC on Chiralpak AD","volume":"46","author":"Gyllenhaal","year":"2008","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8718","DOI":"10.1016\/j.chroma.2011.10.014","article-title":"Unusual chromatographic enantioseparation behavior of naproxen on an immobilized polysaccharide-based chiral stationary phase","volume":"1218","author":"Xiang","year":"2011","journal-title":"J. Chromatogr. A"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/BF02290397","article-title":"The effect of alcoholic mobile phase modifiers on retention and stereoselectivity on a commercially available cellulose-based HPLC chiral stationary phase: An unexpected reversal in enantiometric elution order","volume":"27","author":"Gaffney","year":"1989","journal-title":"Chromatographia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0021-9673(91)85020-G","article-title":"Reversal of elution order during direct enantiomeric separation of pyriproxyfen on a cellulose-based chiral stationary phase","volume":"588","author":"Okamoto","year":"1991","journal-title":"J. Chromatogr. A"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6554","DOI":"10.1016\/j.chroma.2011.06.068","article-title":"Enantiomer elution order reversal of fluorenylmethoxycarbonyl-isoleucine in high-performance liquid chromatography by changing the mobile phase temperature and composition","volume":"1218","author":"Chankvetadze","year":"2011","journal-title":"J. Chromatogr. A"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.chroma.2013.08.029","article-title":"On the effect of basic and acidic additives on the separation of the enantiomers of some basic drugs with polysaccharide-based chiral selectors and polar organic mobile phases","volume":"1317","author":"Mosiashvili","year":"2013","journal-title":"J. Chromatogr. A"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7450","DOI":"10.1016\/j.chroma.2009.05.081","article-title":"Enantioresolution of basic pharmaceuticals using cellulose tris(4-chloro-3-methylphenylcarbamate) as chiral stationary phase and polar organic mobile phases","volume":"1216","author":"Dossou","year":"2009","journal-title":"J. Chromatogr. A"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.chroma.2019.04.024","article-title":"The effect of temperature on the separation of enantiomers with coated and covalently immobilized polysaccharide-based chiral stationary phases","volume":"1599","author":"Matarashvili","year":"2019","journal-title":"J. Chromatogr. A"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0021-9673(97)00648-1","article-title":"3-Fluoro-, 3-chloro- and 3-bromo-5-methylphenylcarbamates of cellulose and amylose as chiral stationary phases for high-performance liquid chromatographic enantioseparation","volume":"787","author":"Chankvetadze","year":"1997","journal-title":"J. Chromatogr. A"},{"key":"ref_38","unstructured":"(2020, October 04). CPMP\/ICH\/381\/95\u2013ICH Harmonised Tripartite Guideline\u2013Validation of Analytical Procedures: Text and Methodology Q2(R1). Available online: https:\/\/www.ema.europa.eu\/en\/ich-q2-r1-validation-analytical-procedures-text-methodology."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/24\/5865\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:43:55Z","timestamp":1760179435000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/24\/5865"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,11]]},"references-count":38,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["molecules25245865"],"URL":"https:\/\/doi.org\/10.3390\/molecules25245865","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,11]]}}}