High Pressure Liquid Chromatographic Determination of Haloperidol Stability

Abstract

Haloperidol lacks stability when exposed to elevated temperatures and light. Current assay procedures described in the USP do not permit detection or quantitation of degradation products of haloperidol. An HPLC assay for the analysis of haloperidol and the detection of degradation products has been developed. The mobile phase consisted of 40:60 THF:water with 0.75% phosphoric acid. A microbond-apak CN column was used to achieve the separation. Samples were injected using a fixed loop (200 microliter) injector and detection was by a fixed wavelength set at 254 nm. Using this mobile phase, haloperidol gave a retention time of 5.4 minutes. Samples of haloperidol treated with heat (60°C for 48 hours) gave peaks at 5.1 and 6.4 minutes as well as a haloperidol peak at 5.4 minutes. A standard curve of haloperidol concentrations was linear (r=0.99) over the range of 1 μg/ml to 100 μg/ml. The conversion of haloperidol to degradation products was noted after storage under conditions of elevated temperature, exposure to light, and as a function of pH. current USP XX assays for this drug include titration of dissolved haloperidol powder with 0.05N perchloric acid or extraction of the drug from a dose form (i.e., oral solution, injection, tablets) with subsequent ultraviolet spectrophotometric analysis (3). Neither one of these assays permits the detection or quantification of haloperidol degradation products. A high-pressure liquid chromatography (HPLC) assay was developed which overcomes the problems associated with the USP assays (3). This HPLC assay has been modified slightly for the analysis of haloperidol and detection of degradation products in drug solutions exposed to elevated temperatures, light, and as a function of pH.