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The separation capacity of eleven different chiral columns: six polysaccharide\u2010type including three amylose\u2010based (Chiralpak AD, Chiralpak AD\u2010RH and Chiralpak AS) and three cellulose\u2010based (Chiralcel OD, Chiralcel OJ and Lux Cellulose\u20104); three cyclodextrin\u2010 (Quest\u2010BC, Quest\u2010C2 and Quest\u2010CM) and two macrocyclic glycopeptide antibiotic\u2010type (Chirobiotic T and Chirobiotic TAG) were screened using polar organic or reversed\u2010phase mode. Chiralpak AD, based on amylose tris(3,5\u2010dimethylphenylcarbamate) as chiral selector with neat methanol was identified as the most promising system. In order to improve resolution, an orthogonal experimental design was employed, altering the concentration of 2\u2010propanol, column temperature, and flow rate in a multivariate manner. Using the optimized method (85\/15 v\/v methanol\/2\u2010propanol, 40\u00b0C, flow rate: 0.7\u00a0mL\/min) we were not only able to separate the four isomers but also detect 0.1% <jats:italic>S<\/jats:italic>\u2010enantiomer as chiral impurity in <jats:italic>R<\/jats:italic>\u2010tofisopam. This is important since the latter is under development as a single enantiomeric agent. Thermodynamic investigation revealed an unusual entropy and enthalpy\u2010entropy co\u2010driven controlled enantioseparation on Chiralcel OJ and on Chiralpak AD column, respectively. Our newly developed HPLC method was validated according to the ICH guidelines and its application was tested on a pharmaceutical formulation containing the racemic mixture of the drug. As a further novelty, a separate circular dichroism method was applied for the investigation of the interconversion kinetics of tofisopam conformers, which proved to be crucial for sample preparation and method validation.<\/jats:p>","DOI":"10.1002\/elps.201800220","type":"journal-article","created":{"date-parts":[[2018,7,12]],"date-time":"2018-07-12T05:40:37Z","timestamp":1531374037000},"page":"2566-2574","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Enantiomeric quality control of <i>R<\/i>\u2010Tofisopam by HPLC using polysaccharide\u2010type chiral stationary phases in polar organic mode"],"prefix":"10.1002","volume":"39","author":[{"given":"Mohammadhassan","family":"Foroughbakhshfasaei","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy Semmelweis University  Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zolt\u00e1n\u2010Istv\u00e1n","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy University of Medicine and Pharmacy of T\u00eergu Mure\u015f  Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arash","family":"Mirzahosseini","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy Semmelweis University  Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e9ter","family":"Horv\u00e1th","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy Semmelweis University  Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerg\u0151","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy Semmelweis University  Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,8,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00542458"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00427652"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2860(86)87065-X"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm050552y"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/chir.530010405"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(00)00269-3"},{"key":"e_1_2_8_8_1","first-page":"2719","volume":"12","author":"Fellegvari I.","year":"1989","journal-title":"J. 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