Abstract

GENERIC APPROACH FOR LOW LEVEL DETERMINATION OF 2- HYDROXY ETHYL HYDRAZINE IN PHARMACEUTICAL INGREDIENTS BY GC-MS USING CHEMICAL DERIVATIZATION

Pavani Jagu*, M.A. Krishna Kumar, R. Navaneeswari

Abstract

2-Hydroxy Ethyl Hydrazine (2-Hydrazinyl Ethanol) is being recognized as potential genotoxic impurity (PGI). A sensitive and generic GC-MS method was developed and validated for the determination of 2-Hydroxy Ethyl Hydrazine in Pharmaceutical compounds. The method is based on the derivatisation of 2-Hydroxy Ethyl Hydrazine with Benzaldehyde to form N-benzylidene-2- phenyloxazolidin-3-amine. GC-MS method employing Agilent 1701 capillary column (30 m × 0.32 mm; 0.25μm), with Electron Impact Ionisation (EI) in Selected Ion Recording (SIR) mode was employed. The proposed method was specific, linear, accurate, rugged and precise. The calibration curve showed good linearity over the concentration range of 0.02 μg/mL to 0.3 μg/mL and the correlation Coefficient was greater than 0.999. Method had very low Limit of detection (LOD) and Limit of quantification (LOQ) as 0.006 μg/mL and 0.02 μg/mL respectively. Accuracy was observed within 80% to 120%. The validated method yielded good results of selectivity, linearity, precision and accuracy and this method can be further extended as a good quality control tool for low level quantitation of 2-Hydroxy Ethyl Hydrazine impurity in API’s. API's or any Pharmaceutical product.

Keywords: 2-Hydroxy Ethyl Hydrazine, Benzaldehyde, GC-MS, genotoxic impurity, trace analysis, Active pharmaceutical ingredient.