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Background: A selective chiral high-performance liquid chromatography (HPLC) method was developed and validated to separate and quantify the (d) and (l) carbinoxamine enantiomers in human plasma. Methods: Plasma samples were extracted by liquid-liquid extraction. The separation of carbinoxamine enantiomers and internal standard (IS, pargeverine hydrochloride) was achieved on an amylose tris(5-chloro-2-methylphenylcarbamate) column with a mobile phase of n-Hexane/isopropanol/ethanol/diethyl amine (850:75:75:0.1, v/v/v/v) at a flow rate of 0.8 mL/min. The ultraviolet (UV) detection wavelength was set at 220 nm. Results: Baseline separation of carbinoxamine enantiomers and IS, free from endogenous interferences, was achieved in less than 15 min. Ratio of peak area of each enantiomer to IS was used for quantification of plasma samples. Linear calibration curves were obtained over the range of 20-7500 g/mL in plasma for both enantiomers (R 2 > 0.99). The mean extraction recoveries were 103.8 ± 1.5 and 94.5 ± 1.8 % for (d) and (l) enantiomers of carbinoxamine enantiomers and 96.35 % for IS from human plasma. The mean relative error (RE %) of accuracy and the mean relative standard deviation (RSD %) of intra-day and inter-day precision for both enantiomers were <10 %. Conclusions: The method was validated with accuracy, precision, recovery, and stability and can be used to determine the pharmacokinetics of carbinoxamine enantiomers in human plasma.

A selective chiral ultra fast liquid chromatography (UFLC-DAD) method was developed and validated to separate and quantify the (d)-and (l)-enantiomers of doxylamine in rat plasma. After extraction of the plasma samples with acetonitrile, the separation of doxylamine succinate enantiomers and internal standard (I.S., diphenhydramine hydrochloride) was achieved on a cellulose Tris (4-chloro,3-methylphenylcarbamate) column with a mobile phase of 20 mM ammonium bicarbonate buffer-acetonitrile (65:35 v/v) with 0.15% diethylamine in the buffer at a flow rate of 1.0 mL/min. The diode array (DAD) detection wavelength was set at 220 nm. The peaks obtained were identified as (d) and (l) by injecting the pure (d) form into the liquid chromatography and comparing the chromatograms. The effect of column oven temperature on the retention of doxylamine and mobile phase variables which have an effect on the enantiomers separation like ionic strength, type and concentration of organic modifier was studied. Linear calibration curves were obtained over the range of 100-1400 ng/mL in plasma for both enantiomers (R 2 > 0.995). The mean extraction recoveries were 94.5-104.7% of rat plasma. The mean relative standard deviation (RSD%) of accuracy and intra-day and inter-day precision for both enantiomers were 610%. The method can be further applied to determine the pharmacokinetics of (d)-and (l)-enantiomers in rat plasma.ª 2015 Production and hosting by Elsevier B.V. on behalf

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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 (R = 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.