Development and validation of an HPLC method for determination of ziprasidone and its impurities in pharmaceutical dosage forms.

Ziprasidone is known as a novel "atypical" or "second-generation" antipsychotic drug. A sensitive and reproducible method was developed and validated for determination of ziprasidone and its major impurities, which are significantly different in polarity. The separation is performed on a Waters Spherisorb octadecylsilyl 1 column (5.0 microm particle size, 250 x 4.6 mm id) using a gradient with mobile phase A [buffer-acetonitrile (80+20, v/v)] and mobile phase B [buffer-acetonitrile (10+90, v/v)] at a working temperature of 25 degrees C. The buffer was 0.05 M KH2PO4 solution with an addition of 10 mL triethylamine/L solution, adjusted to pH 2.5 with orthophosphoric acid. The flow rate was 1.5 mL/min, and the eluate was monitored at 250 nm using a diode array detector. Optimization of the experimental conditions was performed using partial least squares regression, for which four factors were selected for optimization: buffer concentration, buffer pH, triethylamine concentration, and temperature. The proposed validated method is convenient and reliable for the assay and purity control in both raw materials and dosage forms.

Preparation and characterisation of phenytoin-loaded alginate and alginate-chitosan microparticles.

We aimed to prepare and investigate microparticles with the varying contents of calcium gelling ion, loaded with phenytoin, a standard antiepileptic agent, in its acidic form. Two different methods of alginate-based microparticles preparation were used: with and without treatment with chitosan. Furthermore, two standard procedures, the one-stage and the two-stage, were applied. Microparticle size of 12 one-stage formulations ranged from 466 to 636 mum. Both types of formulations, chitosan-treated and nontreated, appeared to be highly loaded with the model drug (91-96%). The chitosan-coated alginate-based microparticles prepared by the one-stage procedure exhibited kinetics of phenytoin liberation comparable to a similar sustained release system that had been tested at pH 6.8, as published earlier. As the gel erosion of alginate-based microparticles should be potentiated by the higher pH (used in the present study at pH 7.4), the most favorable of 12 formulations, with the liberation half-time of about 2 hr, seemed to be eligible for further modifications. Counterintuitively, the applied two-stage procedure did not appear to beneficially affect the dissolution behavior of phenytoin when tested in two formulations, which makes further modifications necessary.

Chemometrically assisted development and validation of LC-UV and LC-MS methods for simultaneous determination of torasemide and its impurities.

Complete evaluation of chromatographic behavior and establishment of optimal experimental conditions for determination of torasemide and its four impurities are determined by experimental design. Fractional factorial and 3(n) full factorial design were employed for efficient and rapid optimization of liquid chromatography-ultraviolet and liquid chromatography-mass spectrometry (LC-MS) methods. Separation is achieved on a Zorbax SB C(18) analytical column (250 x 4.6 mm, 5 µm) with mobile phase consisting of acetonitrile and 10 mM ammonium formate (pH 2.5 with formic acid) in gradient mode. The flow rate is 1 mL min(-1), the temperature of the column is 25 °C and UV detection is performed at 290 nm. The efficiency of ionization in electrospray ionization is higher than in atmospheric pressure chemical ionization mode; therefore, it is further used for analysis of torasemide and its impurities. Both methods meet all validation criteria. The calibration curves show high linearity with the coefficients of correlation (r) greater than 0.9982. The obtained recovery values (95.78-104.92%) and relative standard deviation values (0.12-5.56%) indicate good accuracy and precision. Lower limit of detection (LOD) and limit of quantitation (LOQ) values are obtained with the LC-MS method, indicating higher sensitivity of the proposed method.