A Novel Validated GC-MS/MS Method for the Estimation of N-Nitroso Dimethyl Amine and N-Nitroso Diethyl Amine in Zidovudine.

Abstract

A novel method has been developed for the estimation of N-Nitroso dimethyl amine impurities (NDMA) and N-Nitroso diethyl amine (NDEA) in Zidovudine by using Gas chromatograph Triple Quadrupole Mass with Liquid autosampler (GC-MS/MS) and the method is validated as per International Conference on Harmonization recommendations. Sample analysis was executed for Zidovudine by developed method. Both NDMA and NDEA were detected in below quantitation limit for the Zidovudine batches. Efficient chromatographic separation was achieved on a DB-WAX 30m length × 0.25mm internal diameter, 0.5-μm film thickness, Triple quad-8040 GC-MS/MS. Quantification was carried out at Triple quad electron ionization source was at a column flow of 1.5mL/min at a column oven temperature 50°C. The precision was in the range of 0.9-2.5% for NDMA and 0.8-2.3% for NDEA, and regression analysis shows as r value (correlation coefficient) of is >0.99. This method is capable to detect the NDMA and NDEA impurities in Zidovudine at a level of 0.006ppm for limit of detection and 0.018ppm for limit of quantitation with respect to test concentration of 66.66mg/mL.