Supported liquid extraction and LC-MS-MS determination of iloperidone and olanzapine in rat plasma: Application to a pharmacokinetic study.

A sensitive, selective rapid bioanalytical assay method was developed and quantification of iloperidone (ILP) and olanzapine (OLZ) in rat plasma was done by mass spectrometry. Systematic sample preparation and extraction procedure were carried out by supported liquid extraction using dichloromethane to extract both the eluents (ILP and OLZ) from rat plasma samples. The extorted samples were injected on a selective Waters XTerra® C18 reverse-phase bonded column (250 × 4.6 mm i.d., 5 µm) using acetonitrile and 15 mM ammonium formate containing 0.05% trifluoroacetic acid (60:40 v/v) for isocratic elution mode and detected by mass spectrometry. Calibration curves were drawn with the respective assay statistical data and showed linear regression coefficients greater than 0.9996 over the concentration ranges 2-5,000 ng/mL for ILP and OLZ, respectively. The absolute mean recoveries were found to be in the replicate range of 87.12-94.47%, respectively. The obtained results by the method revealed good intra and interday assay performance in terms of 1.70-5.90% precision and 0-5% accuracy. The validated bioassay method has been successfully applied to the pharmacokinetics in rats.

Development and Validation of Stereo Selective Method for the Separation of Razoxane Enantiomers in Hydrophilic Interaction Chromatography.

A novel sensitive and high throughput chiral hydrophilic interaction chromatographic (HILIC) method was developed to separate razoxane enantiomers namely levrazoxane (R-isomer) and dexrazoxane (DEX) in pharmaceutical active ingredient samples. A systematic chiral chromatographic screening system was employed in using multiple HPLC chromatographic modes on various polysaccharide based chiral columns to obtain a potential separation between enantiomers. HPLC separation was achieved using a mobile phase of aqueous 10 mM ammonium bicarbonate and mixture of organic modifiers (70/30, v/v) in the ratio of (5/95, v/v) on an immobilized polysaccharide based chiral stationary phase namely CHIRALPAK IE-3. The chromatographic resolution between the enantiomers was found to be not <8 in the developed method. The values of the limit of detection and limit of quantification of DEX and levrazoxane were found to be 0.0037, 0.011 and 0.0043, 0.013 µgmL-1, respectively. The validated method yielded good results regarding precision, linearity, selectivity and found to be superior in sensitivity when compared to reported method for the accurate quantification of undesired enantiomer.

Thermodynamic evaluation of immobilized cellulose tris(3,5-dichlorophenylcarbamate) as a stationary phase for liquid chromatographic separation of darunavir enantiomers.

Liquid chromatographic separation of darunavir (DRV) enantiomers was studied on Chiralpak IC column containing immobilized cellulose tris(3,5-dichlorophenylcarbamate) using a variety of mobile phase solvents at different temperatures. The separations were accomplished under normal phase conditions using different compositions of n-hexane, organic modifier (2-propanol, ethanol or 1-propanol) and diethyl amine (0.1%) as mobile phase solvents. The effect of volume and nature of organic modifier and column temperature on retention, separation and resolution were studied. Van't Hoff plots (ln k' vs 1/T) were drawn from the chromatographic retention data to calculate to apparent thermodynamic parameters and explain the interactions between the DRV enantiomers and cellulose tris(3,5-dichlorophenylcarbamate) immobilized on silica.