Application of chaotropic effect in reversed-phase liquid chromatography of structurally related phenothiazine and thioxanthene derivatives

• Published in: Journal of Chromatography A Vol. 1192; no. 2; pp. 218 - 224
• Main Authors: Flieger, J., Świeboda, R.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 30.05.2008; Amsterdam; New York: Elsevier; Elsevier
• Subjects: Analysis; Analytical chemistry; Antipsychotic Agents - analysis; Biological and medical sciences; Chaotropic salts; Chemical Phenomena; Chemistry; Chemistry, Physical; Chromatographic methods and physical methods associated with chromatography; Chromatography, High Pressure Liquid; Exact sciences and technology; General pharmacology; Indicators and Reagents; Medical sciences; Other chromatographic methods; Perchlorates - chemistry; Pharmacology. Drug treatments; Phenothiazine and thioxanthene derivatives; Phenothiazines - analysis; Quantitative Structure-Activity Relationship; Retention behavior; RP-HPLC; Sodium Compounds - chemistry; Solvents; Thioxanthenes - analysis; RP-HPLC; Phenothiazine and thioxanthene derivatives; Retention behavior; Chaotropic salts; Cluster analysis; Sulfur nitrogen heterocycle; Phase composition; Property composition relationship; Thioxanthene derivatives; Neuroleptic; Psychotropic; HPLC chromatography; Retention factor; Phenothiazine derivatives; Tricyclic compound; Mobile phase; Reversed phase chromatography; Sulfur heterocycle; Ultraviolet detector; Chaotropic anion; Counter ion; Aromatic compound; Chemometrics
• DOI: 10.1016/j.chroma.2008.02.117
• ISSN: 0021-9673

Chromatographic behavior of two main classes of neuroleptics, derivatives of phenothiazine and thioxanthene in RP systems modified by anionic additives: sodium perchlorate and sodium hexafluorophosphate possessing chaotropic properties, was examined. Influence of the method of pH lowering (by addition of acids: trifluoroacetic or perchloric or by adding the appropriate concentration of phosphate buffer) and the kind of organic modifier in the mobile phase (methanol, acetonitrile) were estimated. Stability of complexes created between protonated drugs and anions of added salts was evaluated by comparison of their desolvation parameters ( K), limiting retention factors for unsolved molecules calculated on the basis of chromatographic data. Experimentally obtained parameters were used in QSAR studies. It appeared that chosen parameters reflect not only physico-chemical properties of analytes but also contain information about the strength of their antipsychotic activity. Multidimensional cluster analysis has been performed. On the basis of the results obtained, it could be concluded that chaotropic systems can generate useful parameters for further QSAR studies.