Abstract

QUANTITATIVE MEASUREMENT OF TRACE LEVELS OF RESIDUAL HYDROXYLAMINE HYDROCHLORIDE BY A SIMPLE GAS CHROMATOGRAPHIC METHOD AND ITS APPLICATION IN DRUG SUBSTANCE

Swarup Prabhune*, Praveen Kumar Darsi, Manish Gangrade and Jeenet Jaychandran

Abstract

A simple and rapid gas chromatographic method has been developed for the determination of residual Hydroxylamine hydrochloride in drug substance as Paliperdione. Hydroxylamine hydrochloride is treated as Potentent ial Genotoxic impur ity (GTI) and its control is shown less than 1.8 ppm level. The proposed method is based on a simple gas chromatographgic technique employing flame ionization detector and 100% Dimethylpolysiloxane as a stationary phase. The proposed method is simple, cost effective, sensitive, and specific, and showed reproducible results. Linearity of detector response was established up to 2.7μ g/ml and the detection limit was 0.45 μ g/ml for Hydroxylamine hydrochloride. The presented method proposes simple derivatization of Hydroxylamine hydrochloride to Acetone oxime using diluent as composition of water and acetone. Specificity of Method was checked and no interference of organic solvents (used in the paliperidone process) was observed. The proposed method has a potential to check and control the traces of hydroxylamine hydrochloride in drug substance. The results from all parameters proved that the method was suitable for determining the residual Hydroxylamine hydrochloride in drug substance. The novelty of the proposed method lies in attributes such that it uses a simple flame ionization detector unlike use of high end Mass spectrometer detectors described in most of the methods reported in literature[7]. The method is simple, yet accurate and efficient, and can be used in any Research or Industrial laboratory where Gas Chromatograph with Flame ionization detector is available.

Keywords: Gas chromatography, Genotoxic, Hydroxylamine hydrochloride, FID.