Abstract

DEVELOPMENT OF HEADSPACE GAS CHROMATOGRAPHY-MASS SPECTROMETRY (GCHS-MS) METHOD FOR THE DETERMINATION OF TRACE LEVEL N-NITROSOMORPHOLINE (NMOR) IMPURITY IN ALLOPURINOL

Tabrez Shaikh*, Amit Gosar, Amit Joglekar and Sandeep Mahatre

ABSTRACT

A selective and highly sensitive Headspace Gas Chromatography-Mass Spectrometry (GCHS-MS) method is developed for the determination of trace level N-nitrosomorpholine (NMOR) carcinogenic impurity in Allopurinol drug substances. The method is validated as per International Council for Harmonisation (ICH) guidelines, for which the limit of detection and limit of quantitation obtained were 0.002 ppm and 0.006 ppm respectively. The correlation coefficient found for the linearity study was 0.9961 in the concentration range between 0.015 ppm and 0.045 ppm. The recovery for N-nitrosomorpholine in Allopurinol drug substance obtained was between 95.56% and 106.67 % ensuring the accuracy of the method. The method was precise with %RSD for precision at LOQ, repeatability and intermediate precision was less than 5%. The developed method meets all the validation acceptance criteria and is found to be specific, selective, linear, precise, and accurate. The validated method can be adapted to determine N-nitrosomorpholine in Allopurinol drug substance (API).

Keywords: Allopurinol, Nitrosamine, N-nitrosomorpholine, Development and Validation.