Method Development and Validation of N-Nitros...

Method Development and Validation of N-Nitrosodimethylamine (NDMA) Content In Metformin Hydrochloride Drug Substance By LC-MS/MS

Author Name : Dr. Rahul Kumar, Harendra Singh

ABSTRACT

A LC-MS/MS method was developed for determination of N-Nitrosodimethylamine using Zorbax SB Phenyl (150 X 4.6) mm; 3.5µm and a mobile phase of 0.2% formic acid in water: 0.1% formic acid in Methanol with gradient, at flow rate of 0.5 ml/min with MS detector. The mass of N-Nitrosodimethylamine was found 74.95 in APCI⁺ mode and the retention time was found 7.0 minutes. The proposed method was validated for System suitability, Specificity, Linearity, LOD and LOQ, Recovery, Precision, Range and Solution stability. All the parameters were found within the acceptable limits. Linearity of N-Nitrosodimethylamine was in the range of LOQ to 150% of specification level. LC-MS/MS method was specific, accurate, precise and suitable for the analysis of N-Nitrosodimethylamine in Metformin Hydrochloride drug substance.

Keywords: Liquid chromatography with mass spectrometry (LC-MS/MS), Nitrosamine impurity, ICH guideline and Method Validation.