Enantioselective UFLC Determination of Hydroxyzine Enantiomers and Application to a Pharmacokinetic Study in Rabbits.
Hydroxyzine is the first generation H1 receptor antagonist drug that is now marketed as a racemic mixture. The paper describes a validated enantioselective liquid chromatography method for the resolution of hydroxyzine enantiomers and cyclizine (internal standard) from 200 µL of rabbit plasma by liquid-liquid extraction technique using n-hexane and isopropanol. Hydroxyzine enantiomers were resolved at 10.2 and 11.1 min with good baseline resolution (Rs= 1.9) on a Lux amylose-2 chiral column (250 mm × 4.0 mm, 5 microns) at ambient room temperature. The mobile phase consisted of n-hexane-ethanol-diethylamine (90:10:0.1 v/v/v) pumped at 0.9 mL/min. The eluted enantiomers were detected at 254 nm. The linear calibration curve was constructed in the range 20-1000 ng/mL for both the (S)- and (R)-enantiomers. The intra- and inter-day precision were 0.16-2.6% and 0.2-1.92% for (S)-hydroxyzine and (R)-hydroxyzine, respectively. The method was successfully applied to determine the kinetic parameters of (S)- and (R)-hydroxyzine enantiomers in rabbits. The results illustrate that the disposition of hydroxyzine enantiomers is not stereoselective in rabbits.
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS University, Mysuru 570015, India tadiboyina.sirisha@gmail.com.
Tadiboyina
T
Sirisha
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS University, Mysuru 570015, India.
Bannimath
B
Gurupadayya
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS University, Mysuru 570015, India.
Bharath Kumar
BK
Inturi
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS University, Mysuru 570015, India.
Madhusudhan
M
Purohit
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006919:Hydroxyzine / Q000032:analysis* / Q000097:blood / Q000737:chemistry; D010599:Pharmacokinetics; D011817:Rabbits; D015203:Reproducibility of Results; D013237:Stereoisomerism
D006919:Hydroxyzine