A new group of 5,5-diarylhydantoin derivatives bearing a methylsulfonyl COX-2 pharmacophore at the para position of the C-5 phenyl ring were designed and synthesized as selective COX-2 inhibitors. In vitro COX-1/COX-2 inhibition structure-activity relationships identified 5-[4-(methylsulfonyl)phenyl]-5-phenyl-hydantoin (4) as a highly potent and selective COX-2 inhibitor (COX-2 IC50 = 0.077 μM; selectivity index > 1298). It was more selective than the reference drug celecoxib (COX-2 IC50 = 0.060 μM; selectivity index = 405). A molecular modeling study where 4 was docked in the binding site of COX-2 indicated that the p-MeSO2 COX-2 pharmacophore group on the C-5 phenyl ring is oriented in the vicinity of the COX-2 secondary pocket. The results of this study showed that the type of substituent on the N-3 hydantoin ring substituent is important for COX-2 inhibitory activity.

& A reversed-polarity capillary electrophoretic method based on application of sodium dodecyl sulfate (SDS) micelles as the carriers was developed for separation and determination of Fexofenadine (FXN) hydrochloride and its three major structural impurities in bulk and a tablet dosage form. CE analysis was performed using untreated fused-silica capillary of 50 lm internal diameter and 75-cm total length (25-cm effective length). The voltage applied of À25 kV at 25 C, and the detection wavelength was set at 225 nm. The running buffer was a 150 mM phosphate buffer at pH ¼ 3.0, containing 22 % v=v acetonitrile and 25 mmol SDS. Terfenadine was used as the internal standard (IS). The proposed method was found selective for determination of the main drug and its major impurities. The limit of quantification (LOQ) for FXN and impurities D10, D11, and A were found 70 lg=mL, 50 lg=mL, 80 lg=mL, and 100 lg=mL, respectively. The regression data obtained from the calibration plots indicated linear relationship (r 2 ¼ 0.997) over the concentration range of 70-500 lg=mL of FXN. Repeatability and reproducibility of the method, assessed as intra-day and inter-day variation and expressed as RSD ( %), were less than 4 % for relative peak area. Then, the method was applied for the determination of FXN in bulk and a tablet dosage form.

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