Determination of Pharmaceutical Preparations by Gas Chromatography. VI. Determination of p-Chlorophenol in Clofibrate Capsule using Flame Photometric and Flame Thermionic Detector

Gas-liquid chromatographic determination of nanogram quantities of p-chlorophenol (PCP) in Clofibrate capsule was examined. Clofibrate in capsule preparations contains parabens which are added as a preservative to the capsules made of gelatin. J. P. IX method is necessary to separate PCP and Clofibrate-parabens before color reaction and is very time consuming. This proposed method utilizes derivatization of PCP and parabens to their diethylphosphate esters with diethyl chlorophosphate and sodium methoxide in hexane at 50°for 30 min in the presence of Clofibrate. The diethylphosphate esters are determined by flame photometric detector (FPD) and flame thermionic detector (FTD) on a column (2.5mm×2m) of 3.5% silicone JXR on Chromosorb G. HP (80-100 mesh), at 190°, nitrogen as a carrier gas at the flow rate of 30 ml/min. Clofibrate, PCP-diethylphosphate ester, and paraben-diethylphosphate esters were separated under this condition. PCP was determined by the internal standard method using p-bromophenol diethylphosphate ester. Coefficient of variation of peak height ratio for 3.87, 5.80, and 7.74 μg of PCP in 10 ml were 0.87%, 0.56%, and 0.56% with FTD, and 1.50%, 0.57%, and 0.56% with FPD, respectively. PCP in commercial preparations was 1.6 to 5.1 ppm.