ABSTRACT
The chromatographic behavior of six calix[n]arene phases (n=4, 6, 8) and one calix[4]resorcinarene phase is described for the separation of cis- and trans-isomers of three thioxanthene (flupentixol, clopenthixol, chlorprothixene) and one benz[b,e]oxepin derivative (doxepin). The influences of two different organic modifiers (MeOH, MeCN) for the separation of the isomers on every column are described. Different selectivities of the stationary phases exist as a function of the ring size of the calixarenes and their substitution at the "upper rim" with p-tert.-butyl groups. Furthermore, the influence of free phenol groups on the resorcinarene phase is discussed. Relations between structural elements of the analytes and the retention behavior on the stationary phases are found. The selectivity of the calixarene and resorcinarene stationary phases is compared with a RP-C18 phase containing the same base silica. Advantages of the resorcinarene as well as of the calixarene columns exist for the separation of cis- and trans-isomers of three compounds dependent from the substitution in position 2 of the thioxanthenes, respectively the kind of the basic side chain of all substances.
Subject(s)
Dibenzoxepins/isolation & purification , Macromolecular Substances , Phenylalanine/analogs & derivatives , Phenylalanine/chemistry , Thioxanthenes/isolation & purification , Calixarenes , Chlorprothixene/chemistry , Chlorprothixene/isolation & purification , Chromatography, High Pressure Liquid , Clopenthixol/chemistry , Clopenthixol/isolation & purification , Dibenzoxepins/chemistry , Doxepin/chemistry , Flupenthixol/chemistry , Flupenthixol/isolation & purification , Hydrogen-Ion Concentration , Indicators and Reagents , Isomerism , Thioxanthenes/chemistryABSTRACT
The development of a reversed-phase liquid chromatographic method, using a mobile phase containing a mixture of anion and cation ion-pairing agents and a base-deactivated octyldecylsilyl column as stationary phase, is described for the control of all known impurities in (Z)-chlorprothixene hydrochloride (bulk drug). Validation of the method showed it to be reproducible, selective for both (Z) chlorprothixene hydrochloride and its E-isomer, accurate and linear over the concentration range of analysis with a limit of detection of 0.3 microgram ml-1.
