ABSTRACT
A capillary electrophoresis method was developed to determine the impurity of etodolac enantiomers. (2-Hydroxypropyl)-beta-cyclodextrin (HP-beta-CD) was used as a chiral selector and ketoprofen as an internal standard to improve the peak area precision. The seperation of the etodolac enantiomers was achived within 35 min at 15 degrees C and its highest resolution was about 4.0 using phosphate buffer (0.1 M, pH 6.0) with 15 mM HP-beta-CD and UV detection at 225 nm with a reference wavelength at 360 nm. This method allowed determination of 0.2% of (R)-(-)-etodolac in (S)-(+)-etodolac and method validation showed adequate linearity over the required range.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemistry , Etodolac/chemistry , beta-Cyclodextrins/chemistry , 2-Hydroxypropyl-beta-cyclodextrin , Buffers , Electrochemistry , Electrophoresis, Capillary , Excipients , Hydrogen-Ion Concentration , Reference Standards , Reproducibility of Results , Stereoisomerism , TemperatureABSTRACT
A coupled achiral-chiral high performance liquid chromatographic method was developed and fully validated for the determination of bevantolol enantiomers, (-)-(S)-bevantolol and (+)-(R)-bevantolol, in human plasma. Plasma samples were prepared by solid phase extraction with Sep-Pak Plus C18 cartridges followed by HPLC. Bevantolol enantiomers and (+)-(R)-Propranolol as internal standard (IS) were preseparated from interfering components in plasma on a Phenomenex silica column and bevantolol enantiomers and IS were resolved and determined on a Chiralcel OJ-H chiral stationary phase. The two columns were connected by a switching valve equipped with silica precolumn. The Precolumn was used to concentrate bevantolol in the eluent from the achiral column before back flushing onto chiral phase. A detailed validation of the method was performed accordingly to FDA guidelines. For each enantiomer the assay was linear between 20 and 1600 ng/ml. The quantification limits of both bevantolol enantiomers were 20 ng/ml. The intraday variation was between 1.07 and 12.64% in relation to the measured concentration and the interday variation was 0.91 and 11.79%. The method has been applied to the determination of (-)-(S)- and (+)-(R)-bevantolol in plasma from healthy volunteers dosed with racemic bevantolol hydrochloride.
Subject(s)
Chromatography, High Pressure Liquid/methods , Propanolamines/blood , Chromatography, High Pressure Liquid/instrumentation , Chromatography, High Pressure Liquid/statistics & numerical data , Drug Stability , Humans , Propanolamines/chemistry , Propanolamines/pharmacokinetics , Sensitivity and Specificity , StereoisomerismABSTRACT
A number of wogonin derivatives have been synthesized as congeners of wogonin and evaluated for their inhibitory activities of PGE2 production. Wogonin derivatives modified at the B ring of wogonin were obtained from 2,4-Dihydroxy-3,6-dimethoxyacetophenone (1) via several steps. Most wogonin derivatives exhibited much reduced inhibitory activities against COX-2 catalyzed PGE2 production compared to that of wogonin. Alkylation of 5,7-phenol groups and substitution at the B ring of wogonin generally caused reduction of inhibitory activity.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Flavanones/pharmacology , Animals , Anti-Inflammatory Agents/chemical synthesis , Cell Line , Cyclooxygenase 2 Inhibitors/pharmacology , Dinoprostone/metabolism , Flavanones/chemical synthesis , Flavonoids/pharmacology , Lipopolysaccharides , Structure-Activity RelationshipABSTRACT
A number of 8-arylflavones have been synthesized as congeners of wogonin and evaluated for their inhibitory activities of PGE2 production. 8-Arylflavones were obtained from commercially available chrysin via two different synthetic pathways. Most 8-arylflavones exhibited much reduced inhibitory activities against COX-2 catalyzed PGE2 production compared to that of wogonin. Functional group replacement at the 8-position of wogonin from methoxy to aryl group caused loss of inhibitory activity. Our present results imply that the functional group at the 8-position of flavones seems to play very important roles for bioactivity.
Subject(s)
Flavonoids/chemical synthesis , Flavonoids/pharmacology , Animals , Cell Line , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/chemical synthesis , Cyclooxygenase Inhibitors/pharmacology , Isoenzymes/antagonists & inhibitors , Isoenzymes/metabolism , Mice , Prostaglandin-Endoperoxide Synthases/metabolismABSTRACT
Vinylated and allylated chrysin analogues were prepared as congeners of prenylated flavonoids and evaluated their anti-inflammatory activity. 8-Substituted chrysin analogues were prepared from 2'-hydroxy-3'-iodo-4',6'-dimethoxyacetophenone in 3 steps. 3-Allylated chrysin analogues were prepared from chrysin in 3 steps. Synthesized chrysin analogues (4, 5 and 8) showed moderate inhibitory activities of PGE2 production from LPS-induced RAW 264.7 cells.