Enantiomeric separation of oxomemazine in rabbit plasma by ultra-fast LC and application in a stereoselective pharmacokinetic study.

Aim: Ultra-fast LC was used to establish a new bioanalytical method for enantiomeric separation of oxomemazine. Methods: The proposed study was carried out using the ultra-fast LC technique with an amylose chiral column. The bioanalytical approach was used in rabbit plasma following US FDA regulations and then extended to oxomemazine enantiomeric separation using metronidazole as the internal standard. Results: The retention times of (R)-oxomemazine, (S)-oxomemazine and the internal standard were found to be 9.511, 10.712 and 6.503 min, respectively. Within-run and between-run precision (percent relative standard deviation) was found to be in the range of 0.018-0.102% for (R)-oxomemazine and 0.028-0.675% for (S)-oxomemazine, whereas accuracy (%) was found to be in the range of 95.971-99.720% for (R)-oxomemazine and 97.199-103.921% for (S)-oxomemazine. Conclusion: The findings revealed that stereospecific distribution of oxomemazine enantiomers does not change significantly.

Bioanalytical chiral chromatographic technique and docking studies for enantioselective separation of meclizine hydrochloride: Application to pharmacokinetic study in rabbits.

Enantiomeric resolution and molecular docking studies of meclizine hydrochloride on polysaccharide-based chiral stationary phase comprising cellulose tris(4-methylbenzoate) chiral selector (150 × 4.6 mm, 3.0 µm) were presented. The mobile phase used was acetonitrile:10mM ammonium bicarbonate (95:05, v/v). The developed technique was used to perform the enantioselective assay of meclizine hydrochloride in its marketed formulation. The elution order of meclizine hydrochloride enantiomers was determined by docking studies. Target compound was extracted from rabbit plasma using protein precipitation technique, followed by development of bioanalytical chiral separation method using the same matrix. Application of the method to determine pharmacokinetic parameters of meclizine hydrochloride enantiomers was performed using Phoenix WinNonlin 8.1 software. The results demonstrated stereoselective disposition of meclizine hydrochloride enantiomers in rabbits.