ANALYSIS AND IDENTIFICATION OF PROCHLORPERAZINE IMPURITIES AND FORCED DEGRADATION PRODUCTS USING A STABILITY-INDICATING HPLC METHOD

Abstract

Prochlorperazine (PCZ) is a phenothiazine drug that was approved by the FDA in 1956. The U.S. Pharmacopeia is currently seeking an improved method for the PCZ drug substance monograph. A new reverse phase HPLC method was developed to separate the impurities and degradants in PCZ and to quantitatively determine the content of PCZ. The developed method applied an Agilent Zorbax SB-C18 column and a gradient mobile phase flow with UV detection for the separation. The method was applied to the separation of U.S. Pharmacopeia (USP) grade PCZ from its impurities. Impurity identification was performed with LC-MS and fraction isolation followed by NMR. Dimeric chlorophenothiazine (CPT) impurities were newly identified in the USP grade PCZ. Forced degradation studies were performed on PCZ under acid, base, oxidation, heat, and photolytic stress conditions. Peak purity assessments using HPLC-photodiode array (PDA) and HPLC-mass spectrometer (MS) detectors demonstrated the developed method to be stability-indicating. The method was validated and was demonstrated to be specific, accurate (recovery > 98.5%), linear (r > 0.999) and sensitive (limit of detection = 0.025 µg/mL or 0.017% of nominal concentration), and suitable for impurity testing and assay of PCZ drug substance.