Issue 38, 2024

Development of a sensitive LC-MS/MS method for determination of N-nitrosopiperazine in levocetirizine

Abstract

Levocetirizine is one of the widely used antihistamines and has the potential to form N-nitrosopiperazine (NPZ) during drug synthesis, manufacturing, or storage. NPZ classified as a nitrosamine is a genotoxic impurity with carcinogenic properties. Controlling the presence of NPZ in the active pharmaceutical ingredient (API) and drug products is crucial with levels ideally maintained below 80 ppm. Herein, we developed a highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique to analyze NPZ levels in levocetirizine API and various formulations. Chromatographic separation was carried out using an F5 column with mobile phases consisting of 2 mM ammonium formate in water and acetonitrile, employing gradient elution mode at a flow rate of 0.2 mL min−1. The column oven temperature was set at 30 °C, and the injection volume was 2 μL. NPZ quantification was achieved using positive electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. The developed method underwent rigorous validation according to regulatory guidelines. The limit of quantification (LOQ) was established at 1 ng mL−1 within the range of 1–50 ng mL−1, covering 10–500% of the specified NPZ limit in drugs. The effectiveness of the method was shown by utilizing it to analyze the NPZ impurity in both levocetirizine API and various drug products, including tablets, capsules, chewables, and syrups. The proposed method and the resulting data would be valuable for determining potentially present impurities in drug substances or products for quality assessment.

Graphical abstract: Development of a sensitive LC-MS/MS method for determination of N-nitrosopiperazine in levocetirizine

Article information

Article type
Paper
Submitted
07 Jun 2024
Accepted
29 Aug 2024
First published
06 Sep 2024

Anal. Methods, 2024,16, 6494-6500

Development of a sensitive LC-MS/MS method for determination of N-nitrosopiperazine in levocetirizine

Y. Lim, A. Kim, Y. Lee and H. Cho, Anal. Methods, 2024, 16, 6494 DOI: 10.1039/D4AY01067A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements