A Rapid LC Method for the Determination of Haloperidol and Its Degradation Products in Pharmaceuticals Using a Porous Graphitic Carbon Column

Abstract

A simple, rapid, and sensitive HPLC method has been developed and validated for the simultaneous determination of haloperidol and its degradation products, such as cis‐4‐[4‐(4‐chlorophenyl)‐4‐hydroxy‐1‐piperidinyl]‐1‐(4‐fluorophenyl)‐1‐butanone N‐oxide, 4‐[4‐(4‐chlorophenyl)‐4‐hydroxy‐1‐piperidinyl]‐1‐(4‐hydroxyphenyl)‐1‐butanone, 4‐[4‐(4‐chlorophenyl)‐3,6‐dihydro‐1(2H)‐piperidinyl]‐1‐(4‐fluorophenyl)‐1‐butanone and trans‐4‐[4‐(4‐chlorophenyl)‐4‐hydroxy‐1‐piperidinyl]‐1‐(4‐fluorophenyl)‐1‐butanone N‐oxide in pharmaceutical formulations. The method was developed using a porous graphitic carbon (PGC) column and an isocratic elution of 55:45 v/v tetrahydrofuran/water containing 0.5% trichloroacetic acid (TCA). The elution of these compounds was monitored at 254 nm with a flow rate of 1 mL min−1. Linearity was observed in the concentration range from 2 to 50 µg mL−1, with a correlation coefficient (R 2) greater than 0.999. The limits of detection were 0.1 µg mL−1 for haloperidol and 0.05 µg mL−1 for the degradation products. Parameters of validation prove the precision of the method and its applicability for the simultaneous determination of haloperidol and its degradation products. The method is fast and one chromatogram separation lasts about 9 min.