ABSTRACT
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.
Subject(s)
Amylose/analogs & derivatives , Chromatography, High Pressure Liquid/methods , Models, Molecular , Pharmaceutical Preparations/chemistry , Pharmaceutical Preparations/isolation & purification , Phenylcarbamates/chemistry , Solid Phase Extraction/methods , Amylose/chemistry , Cetirizine/blood , Cetirizine/chemistry , Cetirizine/isolation & purification , Humans , Mandelic Acids/blood , Mandelic Acids/chemistry , Mandelic Acids/isolation & purification , Molecular Conformation , Pharmaceutical Preparations/blood , Pheniramine/blood , Pheniramine/chemistry , Pheniramine/isolation & purification , Reproducibility of Results , Stereoisomerism , Sulfonamides/blood , Sulfonamides/chemistry , Sulfonamides/isolation & purification , Thiazines/blood , Thiazines/chemistry , Thiazines/isolation & purificationABSTRACT
In medical practices, the determination of enantiomeric ratio of the chiral drugs is very important for their activities, bioavailabilities and biodegradation. Only homochiral medication is safe for humans. The chiral analysis in biological samples is the first and most important step. The present article describes the technical strategies of the enantiomeric resolution of racemic drugs in biological samples. Attempts have been made to describe sample preparation by solid-phase extraction and enantiomeric resolution by chiral high-performance liquid chromatography. Various chiral stationary phases used in chiral separations of racemic drugs have been described. Efforts are also made to discuss the chiral recognition mechanism and future perspectives of chiral analyses in biological samples.
