Chiral separation of ibuprofen and chiral pharmacokinetics in healthy chinese volunteers

Abstract

A rapid, sensitive and stereoselective HPLC method based on chiral column analysis was developed and fully validated for the simultaneous determination of the two enantiomers of ibuprofen in human plasma. Using this method, a chiral pharmacokinetic study of two different ibuprofen tablets, i.e. dexibuprofen tablets and racemic ibuprofen tablets, was carried out on 20 healthy Chinese male volunteers according to a single-dose (400 mg), two-way, cross-over randomized design. When a 'non-chiral calculation method' was used, the statistical analysis showed no significant difference for the pharmacokinetic parameters (AUC0-infinity, AUC0-t, Cmax and tmax) between the two oral formulations, suggesting that they were pharmaceutically bioequivalent. Considering that the pharmacological activity of ibuprofen resides exclusively in the S(+)-enantiomer, and that the unidirectional inversion of the R(-) to the S(+)-enantiomer is incomplete and might be race-dependent, the pharmacokinetic parameters for only the S(+)-enantiomer were further compared and the inversion ratio calculated. It was found that only 25% of R(-)-ibuprofen in the racemic ibuprofen tablets was inverted into S(+)-ibuprofen in the Chinese population, which suggested that dexibuprofen might possess a much stronger pharmacological activity than that of racemic ibuprofen when administered at the same dose.

Analysis of ibuprofen enantiomers in rat plasma by liquid chromatography with tandem mass spectrometry

“…The enantiomers of ibuprofen were separated on a chiral stationary phase column (Chirex® 3005) containing ( R )‐1‐naphthylglycine and 3,5‐dinitrobenzoic acid amide linkage, electron acceptor designed for the separation of carboxylic acids, alcohols, esters, and nonsteroidal anti‐inflammatory agents. There are a number of published methods for the analysis of ibuprofen enantiomers in plasma using UV , fluorescence or MS detection . High sensitivity, short run time, and an easy sample preparation step are required to apply a method to study pharmacokinetics in small experimental animals.…”

Enantioselective analysis of ibuprofen enantiomers in mice plasma and tissues by high‐performance liquid chromatography with fluorescence detection: Application to a pharmacokinetic study

“…administration of individual enantiomer or racemic ibuprofen the ratio of t 0.5 (+)-S-ibuprofen / t 0.5 (−)-R-ibuprofen was only 2. 36 In human, there were small differences in t 0,5 values of each enantiomer after oral intake 2,13,37 or no differences after i.v. 5 or oral administration of ibuprofen.…”

Enhanced enantioselectivity of native α‐cyclodextrins by the synergy of chiral ionic liquids in capillary electrophoresis

“…In the past decades, chromatographic techniques are among the most effective analytical methods available for chiral separation . In addition to HPLC and GC, CE has proven to be a promising enantioseparation tool due to its high separation efficiency, low cost, and diverse separation modes .…”

“…In the past decades, chromatographic techniques are among the most effective analytical methods available for chiral separation [2][3][4][5][6][7]. In addition to HPLC and GC, CE has proven to Article Related Abbreviations: AAIL, amino acid chiral ionic liquid; AML, amlodipine; CIT, citalopram; IL, ionic liquid; NEF, nefopam; SUL, sulconazole; TMA-L-Arg, tetramethylammonium-L-arginine; TMA-L-Glu, tetramethylammonium-L-glutamic acid; TMA-L-Pro, tetramethylammonium-L-proline; TMA-OH, tetramethylammonium hydroxide be a promising enantioseparation tool due to its high separation efficiency, low cost, and diverse separation modes [8][9][10].…”