DEVELOPMENT AND VALIDATION OF A STABILITY-INDICATING HPLC METHOD FOR THE DETERMINATION OF PIZOTIFEN, METHYLPARABEN, AND PROPYLPARABEN IN SYRUP.

A new simple, rapid, and sensitive stability-indicating high-performance liquid chromatography method has been developed and validated for the simultaneous determination of pizotifen, methylparaben, propylparaben, and synthesis impurities A and B of pizotifen in syrup. The separation of these compounds was achieved within 14 min on a Waters X-terra RP18 column using an isocratic mobile phase consisting of acetonitrile/tetrahydrofuran/potassium dihydrogenophosphate 0.1 M at pH 3.5 containing 4.59 mM heptane sulfonate (38:1.5:62, v/v/v). The analysis was performed at a flow rate of 1 mL min−1and a detection wavelength of 220 nm. The selectivity, linearity, and calibration range, accuracy, within and between-days precision, limit of detection and quantification, and recovery were examined as part of method validation. Forced degradation showed that pizo does not undergo degradation under heat, acidic, and basic conditions, but that it was susceptible to oxidation with first-order kinetic degradation. Liquid chromatography coupled with mass spectrometry was used to analyze the degraded samples and tentative structural identification were assigned based upon known reactivity of the drug and molecular weight measurements. [ABSTRACT FROM AUTHOR]