Ultra-sensitive Determination of Nitrosamine Genotoxic Impurities in Atomoxetine Hydrochloride using Headspace GC-MS/MS

Deepak Kumar; Divya Gairola

doi:10.63363/aijfr.2025.v06i06.1591

Ultra-sensitive Determination of Nitrosamine Genotoxic Impurities in Atomoxetine Hydrochloride using Headspace GC-MS/MS

Author(s)	Mr. Deepak Kumar, Dr. Divya Gairola
Country	India
Abstract	Nitrosamine impurities such as N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) have recently attracted intensified regulatory attention owing to their classification as probable human carcinogens and their detection in several pharmaceutical products. Consequently, it is crucial to make sure that these impurities are not present in drug ingredients. The present research has developed and validated a gas chromatography-tandem mass spectrometry (GC-MS/MS) method for the detection of NDMA and NDEA at the trace level in Atomoxetine hydrochloride, a selective norepinephrine reuptake inhibitor used to treat attention-deficit hyperactivity disorder (ADHD). To achieve high sensitivity and selectivity, the method leveraged headspace sampling in conjugation with multiple reaction monitoring (MRM) transitions (NDMA: 74.1 → 44.2; NDEA: 102.2 → 85.1). Excellent specificity has been established by validation, and analyte retention times demonstrated no interference. For both analytes, the technique exhibited a limit of detection (LOD) of 0.01 ppm and a limit of quantification (LOQ) of 0.03 ppm. Precision studies revealed % RSD values of 4.2% and 5.7% respectively, for NDMA and NDEA, whereas recovery studies at the LOQ level demonstrated accuracy of 99% for NDMA and 105% for NDEA. It has been confirmed that NDMA and NDEA were not detected at or above the method’s quantitation limits while the validated method was implemented to three successive batches of Atomoxetine Hydrochloride. In order to ensure compliance with international regulatory guidelines for the genotoxic impurities, the results illustrate that the developed GC-MS/MS method is a robust, sensitive, and reliable technique for the routine monitoring of nitrosamine impurities in Atomoxetine hydrochloride.
Keywords	NDMA, NDEA, Atomoxetine hydrochloride, Nitrosamines, GC-MS/MS, Genotoxic impurities.
Field	Medical / Pharmacy
Published In	Volume 6, Issue 6, November-December 2025
Published On	2025-11-02
DOI	https://doi.org/10.63363/aijfr.2025.v06i06.1591
Short DOI	https://doi.org/g99qq3

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Ultra-sensitive Determination of Nitrosamine Genotoxic Impurities in Atomoxetine Hydrochloride using Headspace GC-MS/MS

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