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.
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