Enantiomeric separation and simulation studies of pheniramine, oxybutynin, cetirizine, and brinzolamide chiral drugs on amylose-based columns.
Solid phase extraction (SPE)-chiral separation of the important drugs pheniramine, oxybutynin, cetirizine, and brinzolamide was achieved on the C18 cartridge and AmyCoat (150 x 46 mm) and Chiralpak AD (25 cm x 0.46 cm id) chiral columns in human plasma. Pheniramine, oxybutynin, cetirizine, and brinzolamide were resolved using n-hexane-2-PrOH-DEA (85:15:0.1, v/v), n-hexane-2-PrOH-DEA (80:20:0.1, v/v), n-hexane-2-PrOH-DEA (70:30:0.2, v/v), and n-hexane-2-propanol (90:10, v/v) as mobile phases. The separation was carried out at 25 ± 1 ºC temperature with detection at 225 nm for cetirizine and oxybutynin and 220 nm for pheniramine and brinzolamide. The flow rates of the mobile phases were 0.5 mL min(-1). The retention factors of pheniramine, oxybutynin, cetirizine and brinzolamide were 3.25 and 4.34, 4.76 and 5.64, 6.10 and 6.60, and 1.64 and 2.01, respectively. The separation factors of these drugs were 1.33, 1.18, 1.09 and 1.20 while their resolutions factors were 1.09, 1.45, 1.63 and 1.25, and 1.15, respectively. The absolute configurations of the eluted enantiomers of the reported drugs were determined by simulation studies. It was observed that the order of enantiomers elution of the reported drugs was S-pheniramine > R-pheniramine; R-oxybutynin > S-oxybutynin; S-cetirizine > R-cetirizine; and S-brinzolamide > R-brinzolamide. The mechanism of separation was also determined at the supramolecular level by considering interactions and modeling results. The reported SPE-chiral high-performance liquid chromatography (HPLC) methods are suitable for the enantiomeric analyses of these drugs in any biological sample. In addition, simulation studies may be used to determine the absolute configuration of the first and second eluted enantiomers.
Department of Chemistry, Jamia Millia Islamia, (Central University) New Delhi, India; Department of Chemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Imran
I
Ali
Zeid A
ZA
Al-Othman
Abdulrahman
A
Al-Warthan
Syed Dilshad
SD
Alam
Javed A
JA
Farooqi
D000688:Amylose / Q000031:analogs & derivatives* / Q000737:chemistry; D017332:Cetirizine / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D008333:Mandelic Acids / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification; D008958:Models, Molecular; D008968:Molecular Conformation; D004364:Pharmaceutical Preparations / Q000097:blood / Q000737:chemistry* / Q000302:isolation & purification*; D010632:Pheniramine / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification; D048448:Phenylcarbamates / Q000737:chemistry*; D015203:Reproducibility of Results; D052616:Solid Phase Extraction / Q000379:methods*; D013237:Stereoisomerism; D013449:Sulfonamides / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification; D013843:Thiazines / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification
D008333:Mandelic Acids; D004364:Pharmaceutical Preparations; D048448:Phenylcarbamates; D013449:Sulfonamides; D013843:Thiazines; D010632:Pheniramine; C080033:Chiralpak AD; D000688:Amylose; C111827:brinzolamide; C005419:oxybutynin; D017332:Cetirizine
SPE-chiral-HPLC; human plasma; mechanism of separation; modeling