Chiral separation of Frovatriptan isomers by HPLC using amylose based chiral stationary phase.

A stereospecific HPLC method for separation of Frovatriptan enantiomers in bulk drug and pharmaceutical formulations was developed and validated on a normal-phase amylose derivertized chiral column. The effects of the organic modifiers namely 2-propanol, ethanol and diethyl amine (DEA) in the mobile phase were optimized to obtain the best enantiomeric separation. Calibration curves were linear over the range of 200-6150 ng/mL, with a regression coefficient (R(2)) of 0.9998. The limit of detection (LOD) and limit of quantification (LOQ) were 65 ng/mL and 200 ng/mL, respectively. The method was accurate and precise and suitable for the intended purpose. Analysis results were compared with the results obtained by using a validated chiral CE method and found to be in very good agreement. This method can be successfully applied to the enantiomeric purity analysis of Frovatriptan in pharmaceutical bulk drug samples and formulations.

A validated chiral CE method for Frovatriptan, using cyclodextrin as chiral selector.

A cyclodextrin modified capillary zone electrophoretic method has been developed for the evaluation of chiral purity of Frovatriptan using sulfobutyl ether beta cyclodextrin (SB-beta-CD) as the chiral selector. The method is highly specific, accurate and reproducible. The method was optimized with a systematic method development approach by optimizing the pH of electrolyte, attempting the separation in different classes of chiral selectors and modifying parameters such as cyclodextrin concentration and the organic modifier type and concentration. The optimized method was validated for specificity, precision, linearity, accuracy and stability in solution using Imidazole as the internal standard. The limit of detection (LOD) and limit of quantification (LOQ) were 1.0 microg/mL and 5.0 microg/mL respectively for each isomer. The method was applied for estimating the chiral purity of various batches of Frovatriptan.

Isolation, synthesis and characterization of impurities in celecoxib, a COX-2 inhibitor.

During the impurity profile of Celecoxib, four polar impurities (impurity I, II, III and IV) and one non-polar impurity (impurity V) with respect to Celecoxib were detected by HPLC. LC-MS has been employed in this impurity profile study. The three polar impurities (I, II and III) were found to be process related while impurities (IV and V) turned out to be isomers. The impurities III, IV and V were isolated with the help of preparative HPLC. The structure of impurities III, IV (ortho-isomer) and V (regio-isomer) were confirmed as [5-(4-methylphenyl)-3-trifluoromethyl-1H-pyrazole], 4-[5-(2'-methyl phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide, and 4-[4-(4'-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-benzenesulfonamide, respectively. The structures of impurities I, II, III and IV were confirmed by synthesis and structural characterization using spectral data. However, the impurity V was not synthesized.