Enantioselective HPLC-DAD method for the determination of etodolac enantiomers in tablets, human plasma and application to comparative pharmacokinetic study of both enantiomers after a single oral dose to twelve healthy volunteers.

An enantioselective high performance liquid chromatographic method with diode array detection (HPLC-DAD) was developed and validated for the determination of etodolac enantiomers in tablets and human plasma. Enantiomeric separation was achieved on a Kromasil Cellucoat chiral column (250 mm × 4.6mm i.d., 5 µm particle size) using a mobile phase consisting of hexane: isopropanol: triflouroacetic acid (90:10:0.1 v/v/v) at a flow rate of 1.0 mL min(-1). The chromatographic system enables the separation of the two enantiomers and the internal standard within a cycle time of 8 min. The resolution between the two enantiomers was 4.25 and the resolution between each enantiomer and the internal standard was more than 2.0. Detection was carried out at 274 nm, and the purity assessment was performed using a photodiode array detector. Solid phase extraction technique using C-18 cartridge was applied to extract the analytes from the plasma samples, and the percentage recovery was more than 95% for the lower quantification limit. The method has been validated with respect to selectivity, linearity, accuracy and precision, robustness, limit of detection and limit of quantification. The validation acceptance criteria were met in all cases. The linearity range for the determination of each enantiomer in human plasma was 0.4-30.0 µg mL(-1) and the limits of quantification of R-etodolac and S-etodolac were 0.20 and 0.19 µg mL(-1), respectively. The validated method was successfully applied to the determination of etodolac enantiomers in tablets and to a comparative pharmacokinetic study of the two enantiomers after the administration of 300 mg single oral dose etodolac racemate tablets to twelve healthy volunteers.

Hewala II ，Moneeb MS ，Elmongy HA ，Wahbi AA ... -  《-》

Analysis of flurbiprofen, ketoprofen and etodolac enantiomers by pre-column derivatization RP-HPLC and application to drug-protein binding in human plasma.

Jin YX ，Tang YH ，Zeng S 《JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS》

Development and validation of an enantioselective HPLC-UV method using Chiralpak AD-H to quantify (+)- and (-)-torcetrapib enantiomers in hamster plasma--application to a pharmacokinetic study.

Trivedi RK ，Dubey PK ，Mullangi R ，Srinivas NR ... -  《JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES》

Chiral liquid chromatography resolution and stereoselective pharmacokinetic study of pioglitazone enantiomers in rats.

A selective chiral high performance liquid chromatographic (HPLC) method was developed and validated to separate and quantify the pioglitazone enantiomers in rat plasma. After extraction of the plasma samples with ethyl acetate, the separation of pioglitazone enantiomers and internal standard (I.S., dexamethasone acetate) was achieved on a cellulose tris (3,5-dichlorophenylcarbamate) column known as Chiralpak IC with a mobile phase of hexane-isopropanol (70:30, v/v) at a flow rate of 1.0mL/min. The ultraviolet (UV) detection wavelength was set at 225nm. Baseline separation of pioglitazone enantiomers and I.S., free from endogenous interferences, was achieved in less than 25min. Ratio of peak area of each enantiomer to I.S. was used for quantification of plasma samples. Linear calibration curves were obtained over the range of 0.25-50μg/mL in plasma for both enantiomers (R(2)>0.9990) with quantitation limit of 0.25μg/mL. The mean extraction recoveries were 82.37-91.38% for pioglitazone enantiomers and 95.76% for I.S. from rat plasma. The mean relative error (R.E. %) of accuracy and the mean relative standard deviation (R.S.D. %) of intra-day and inter-day precision for both enantiomers were <10%. The method was validated with accuracy, precision, recovery and stability and used to determine the pharmacokinetics of pioglitazone enantiomers, after a single oral administration of racemic pioglitazone (30mg/kg). The differences between the pharmacokinetic parameters Cmax, AUC0-24, AUC0-∞, CL/F of (+)-pioglitazone and (-)-pioglitazone were significant, suggesting that the disposition of pioglitazone in rats may be enantioselective. Moreover, the plasma levels of (+)- and (-)-pioglitazone in female rats were apparently higher than that in male rats, respectively.

Du B ，Pang L ，Yang Y ，Shen G ，Zhang Z ... -  《-》

An improved and validated LC method for resolution of bicalutamide enantiomers using amylose tris-(3,5-dimethylphenylcarbamate) as a chiral stationary phase.

Nageswara Rao R ，Narasa Raju A ，Nagaraju D 《JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS》