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.

Recent Advances in Chiral Separation of Antihistamine Drugs: Analytical and Bioanalytical Methods.

Chirality is now a key area in the field of research. Researchers are well versed with analytical separations but at the same time, they are unaware of the growth in the field of chiral separation. According to the United States Food and Drug Administration (US FDA) guidelines, it is mandatory to separate chiral drugs before they are marketed. Chiral separation has gained importance in the last 10 years due to the differential biological responses of the enantiomers in chiral environment. Identical physical and chemical properties of the enantiomers pose a major challenge for the separation of chiral compounds. Further, bioanalytical method development is also necessary to throw light on the fate of separated enantiomers in biological environment. High Performance Liquid Chromatography (HPLC) and Capillary Electrophoresis (CE) are the most widely used techniques for such separation. Antihistamines are a class of drugs that are represented by a wide number of chiral compounds. Hence this review focuses on enantioseparation of chiral antihistamine drugs. It begins with a brief discussion about antihistamine drugs, chiral separation and its need for study, followed by a brief overview of the analytical and bio-analytical work carried out on different chiral antihistamine drugs. The analytical and bio-analytical techniques that are used include HPLC, CE and some new techniques.