Some Applications of Gas Chromatography to the Determination of Drugs

Abstract

The development and application of gas-liquid chromatographic (GLC) methods for the determination of chloramphenicol in pharmaceutical products and lactic acid in cerebrospinal fluid (CSF) is described. Chloramphenicol was found to convert rapidly and quantitatively into a phenyl boronate ester on treatment with phenyl boronic acid. This derivative whose structure was proven by infra-red and 1H nuclear magnetic resonance spectroscopy and mass spectrometry, was found to possess good chromatographic properties. It was eluted from an OV-17 column within 5 minutes and the incorporation of triphenyl benzene as an internal standard enabled a  quantitative response to be achieved. The procedure was found to be applicable to the determination of chloramphenicol in solid, liquid and semi-solid dosage forms after suitable extraction. Details for each procedure are described. The assay was also suitable for the determination of chloramphenicol in degraded samples. This has been illustrated by a study of the stability of chloramphenicol eye-drops-hydrolytic or photochemical decomposition. The hydrolysis reactions were performed at 89°C in solutions of different pH(3-6) or with different buffer concentrations (O.O5N-1.5N). In each case first-order kinetics were observed. Photochemical degradation was used to assess the efficiency of various containers in protecting chloramphenicol eye-drops from light-initiated decomposition. Again, first-order kinetics were observed and the most efficient container studied was an amber soda glass bottle originally used for packing eye/ear/nose drops. This degradation was also followed by high-performance liquid chromatography (HPLC) and this showed that the initial degradation resulted in the formation of p-nitrobenzaldehyde. Lactic acid in cerebrospinal fluid (CSF) was estimated by esterification with ethanol. Diethyl malonate was found to be a useful internal standard for quantitative purposes and this method allowed the analysis of lactic acid in 77 samples of CSF from patients with suspected meningitis. It was found that lactate levels were elevated in cases of bacterial meningitis(> 0.3 mg.ml. -1) where as non-bacterial meningitis cases had normal (below0.2 mg.ml. -1 ) levels.