ABSTRACT
Pure enantiomers are of large interest for several industries. This study was aimed to establish a method for separation of etodolac enantiomers by preferential crystallization after a conglomerate formation of its derivatives. S-(+)-etodolac and R-(-)-etodolac enantiomers were both prepared by classical resolution via crystallization of diastereoisomeric salt with (-)-brucine and (-)-cinchonidine. Enantiomeric purity of etodolac was determined by HPLC method using Chiralcel OD-H column. The pure diastereomeric salt collected from repeated recrystallization was further fractionated by liquid-liquid extraction to pure enantiomers. Etodolac enantiomers were recovered with overall yield more than 20% and the purities were over 99.9%.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Drug Design , Etodolac/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Chromatography, High Pressure Liquid , Crystallization , Etodolac/chemistry , Molecular Structure , StereoisomerismABSTRACT
An analytical CE method was developed for the enantiomeric purity determination of fluvastatin enantiomers. Fluvastatin enantiomers were separated on an uncoated fused silica with 100 mM-borate solution containing 30 mg/mL of (2-hydroxypropyl)-beta-cyclodextrin (HP-beta-CD) as running buffer and fenoprofen as an internal standard. The linearity was observed within a 400-700 microg/mL concentration range (r(2)>or=0.995) for both fluvastatin enantiomers. The repeatability expressed as coefficient of variation (CV) of the method were 0.96 and 0.92% for (+)-3R, 5S and (-)-3S, 5R-fluvastatin, respectively. The limit of detection and quantification for both fluvastatin enantiomers were 1.5 microg/mL and 2.5 microg/mL, respectively.
Subject(s)
Fatty Acids, Monounsaturated/isolation & purification , Hydroxymethylglutaryl-CoA Reductase Inhibitors/isolation & purification , Indoles/isolation & purification , Capillary Electrochromatography , Cyclodextrins , Electromagnetic Fields , Fatty Acids, Monounsaturated/chemistry , Fluvastatin , Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemistry , Indoles/chemistry , Reference Standards , Reproducibility of Results , Solutions , Stereoisomerism , TemperatureABSTRACT
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.
