Preparative resolution of etodolac enantiomers by preferential crystallization method.

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%.

Chiral separation of fluvastatin enantiomers by capillary electrophoresis.

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.

Determination of bevantolol in human plasma by high performance liquid chromatography using solid phase extraction technique.

A method was developed and fully validated for the determination of bevantolol, an adrenergic-receptor blocker, in human plasma. Bevantolol and betaxolol as internal standard (I.S) were extracted from 1 mL of human plasma by solid phase extraction technique using Sep-pak silica cartridge. Chromatographic separation was accomplished under isocratic conditions using a reverse-phase C8 analytical column and mixture of dibasic ammonium phosphate (pH 5.7; 50 mM)-acetonitrile (75:25, v/v) as mobile phase, with a detection wavelength at 220 nm. The method was proved to be specific by testing six different human plasma sources. Linearity was established for the concentration ranges of 40-1600 ng/mL with correlation coefficent of 0.9995. The lower limit of quantification 40 ng/mL with precision of 10.9% as C.V%.

Determination of bevantolol enantiomers in human plasma by coupled achiral-chiral high performance-liquid chromatography.

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.

Chiral purity test of bevantolol by capillaryelectrophoresis and high performance liquid chromatography.

Two methods for the chiral purity determination of bevantolol were developed, namely capillary electrophoresis (CE) using carboxymethyl-beta-cyclodextrin (CM-beta-CD) as a chiral selector and high-performance liquid chromatography (HPLC) using a chiral stationary phase. In the HPLC method, the separation of bevantolol enantiomers was performed on a Chiralpak AD-H column by isocratic elution with n-hexane-ethanol-diethylamine (10:90:0.1, v/v/v) as mobile phase. In the CE method, bevantolol enantiomers were separated on an uncoated fused silica capillary with 50 mM amonium phosphate dibasic adjusted to a pH 6.5 with phosphoric acid containing 15 mM CM-beta-CD as running buffer. Validation data such as linearity, recovery, detection limit, and precision of the two methods are presented. The detection limits of S-(-)-bevantolol were 0.1% and 0.05% for CE and HPLC method, respectively and R-(+)-bevantolol were 0.15% and 0.05% for CE and HPLC method, respectively. There was generally good agreement between the HPLC and CE results.

Preparative method of R-(-)-lbuprofen by diastereomer crystallization.

The economic and effective method for preparation of R-(-)-ibuprofen by diastereomer crystallization was developed. R-(-)-ibuprofen was resolved from racemic ibuprofen by forming R-(-)-ibuprofen-R-(+)-alpha-methylbenzylamine diastereomeric salt with R-(+)-alpha(-methylbenzylamine and crystallization. The purity of R-(-)-ibuprofen-R-(+)-alpha-methylbenzylamine diastereomeric salt was tested and confirmed using HPLC and 1H-NMR method. The pure diastereomeric salt collected from repeated recrystallization was further fractionated by liquid-liquid extraction to the pure enantiomer without racemization. R-(-)-ibuprofen was recovered producing overall yield of 2.4% with the purity more than 99.97%.