Determination of brompheniramine enantiomers in rat plasma by cation‐selective exhaustive injection and sweeping cyclodextrin modified electrokinetic chromatography method

Abstract

A method consisting of cation-selective exhaustive injection and sweeping (CSEI-sweeping) as online preconcentration followed by a cyclodextrin modified electrokinetic chromatography (CDEKC) enantioseparation has been developed for the simultaneous determination of two brompheniramine enantiomers in rat plasma. In this method, analytes were electrokinetically injected at a voltage of 8 kV for 80 s in a fused-silica capillary. Prior to the injection, the capillary was rinsed with 50 mM phosphate buffer of pH 3.5, followed by a plug of a higher conductivity buffer (150 mM phosphate pH 3.5, 20 psi, 6 min) and a plug of water (0.5 psi, 5 s). Separation was carried out applying -20 kV in 50 mM phosphate buffer, pH 3.5, containing 10% v/v ACN and 30 mg/mL sulfated-β-cyclodextrin (S-β-CD). Analytical signals were monitored at 210 nm. The detection sensitivity of brompheniramine enantiomers was enhanced by about 2400-fold compared to the normal injection mode (hydrodynamic injection for 3 s at 0.5 psi, with a BGE of 50 mM phosphate buffer containing 20 mg/mL S-β-CD at pH 3.5), and LLOQ of two enantiomers were both 0.0100 μg/mL. In addition, this method had fairly good repeatability and showed promising capabilities in the application of stereoselective pharmacokinetic investigations for brompheniramine enantiomers in rat.

Bioanalysis of drugs and their metabolites by chiral electromigration techniques (2010–2020)

“…As in the previous decade, there are again a number of CE‐based investigations that dealt with the elucidation of the pharmacokinetics via analysis of the drug or metabolite enantiomers in plasma (Table 2). Examples studied included the drugs ibuprofen [51], mirtazapine [52], ketamine [45,53], chlorpheniramine [54], brompheniramine [55], methadone [56], and S ‐ketamine [57]. Three of the used assays are capable of measuring simultaneously the enantiomers of the parent compound and two or three chiral metabolites and many assays use FASI or CSEI of the analytes from the plasma extracts to enable the determination of ppb blood levels of the compounds of interest.…”

“…The methadone assay was also used to investigate the pharmacokinetics of l ‐methadone and l ‐EDDP after administration of a commercially available combination of l ‐methadone with fenpipramide to isoflurane anesthetized ponies [97]. Similarly, the assays for chlorpheniramine and brompheniramine were found to be applicable to stereoselective pharmacokinetic investigations of their enantiomers in the rat [54,55]. This is shown for brompheniramine with the data presented in Fig.…”

“…4D). Significant differences between enantiomers were also observed for AUC ( d > l ) and half‐life ( l > d ) [55].…”

“…In this article, CE‐based assays and achievements reported in the 2010 to 2020 literature are comprehensively but not exhaustively reviewed. The main focus is on real samples including enantiomer analysis of drugs and metabolites in body fluids and tissues of humans and animals (Tables 1 and 2, [31–58]) and in in vitro preparations (Tables 3 and 4, [46,47,59–84]). In contrast to previous reviews from our laboratory [26,30], articles dealing with enantiomer analysis in fortified body fluids and tissues are not listed.…”

Sol‐gel technique for the preparation of β‐cyclodextrin gold nanoparticles as chiral stationary phase in open‐tubular capillary electrochromatography

“…Pheniramine was used for the clinical treatment of common cold, allergies, and respiratory infections. This clinical treatment is predominantly attributed to the S ‐enantiomer . Zopiclone (( RS )‐6‐(5‐chloropyridin‐2‐yl)‐7‐oxo‐6,7‐dihydro‐5H‐pyrrolo [3,4‐b] pyrazin‐5‐yl‐4‐methyl piperazine‐1‐carboxylate) is a nonbenzodiazepine hypnotic agent used in the treatment of insomnia.…”