A validated LC-MS method for the estimation of genotoxic nitroso amines impurities in empagliflozin

Mubarakunnisa Mohammed; R Gandhimathi

doi:10.53730/ijhs.v6nS9.13022

Authors

Mubarakunnisa Mohammed Research Scholar, Department of Pharmaceutical Chemistry and Analysis, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies (VISTAS), Pallavaram, Chennai-600117, Tamil Nadu, India.
Gandhimathi R
drgmathipharm2017@gmail.com
Department of Pharmaceutical Chemistry and Analysis, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies (VISTAS), Pallavaram, Chennai-600117, Tamil Nadu, India.

Keywords:

Nitrosamine impurities, LC-MS method, ICH, Empagliflozin

Abstract

Background: Nitrosamine impurities are known to be mutagenic and carcinogenic, and even minor exposure to these impurities can result in genotoxicity. Objective: The objective of this study was to develop and validate simple, robust and accurate Liquid Chromatography coupled with Mass spectroscopy (LC-MS) method for estimation of nitroso amine impurities [N-nitroso dimethyl amine (NDMA), N-nitroso diethylamine (NDEA), N-nitroso ethyl isopropylamine (NEIA), N- Nitroso diisopropylamine (NDIPA)] in empagliflozin. Method & Results: Aqueous ammonia buffer (0.10%) in a mixture of methanol (5:95 v/v), flow rate, and injection volume were 0.4mL/min, 20µL, respectively. Linearity was observed in the concentration range of 0.05-0.5 ppm (r2 =1). The retention time of NDMA, NDEA, NEIA and NDIPA were 6.412, 7.172, 7.486 and 7.719, respectively. The method was validated according to ICH guidelines with good reproducibility, and the limits of detection were 0.03 ppm for NDMA, NEIA and NDIPA and 0.02 ppm for NDEA, respectively. The limit of quantitation for NDMA, NEIA and NDIPA was 0.09 ppm and 0.06 ppm for NDEA, respectively. Conclusion: The proposed method is helpful for the best analysis of nitrosamine impurities in dosage forms of empagliflozin within a shorter duration of time.

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