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Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds
Published on: February 16, 2022
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Highly sensitive two-dimensional ion chromatography mass spectrometry method for nitrite determination in
Koudi Zhu1, Michael Kerry2, Barbara Serr2
1Pharma Solutions, IFF, Midland, MI 48640, USA; Department of Chemical Engineering, Vrije Universititeit Brussel, Pleinlaan 2, Brussel 1050, Belgium.
Journal of Pharmaceutical and Biomedical Analysis
|July 9, 2024
Summary
This study developed a sensitive two-dimensional ion chromatography mass spectrometry (2D-IC/MS) method for trace nitrite determination in pharmaceutical excipients like HPMC, crucial for controlling nitrosamine drug impurities.
Area of Science:
- Analytical Chemistry
- Pharmaceutical Science
Background:
- Nitrosamines in drugs pose health risks and are regulated due to potential carcinogenicity.
- Nitrosamine formation is linked to nitrite presence in pharmaceutical excipients.
- Accurate trace nitrite determination in excipients is vital for drug safety and supplier selection.
Purpose of the Study:
- To develop and validate a sensitive analytical method for trace nitrite determination in hydroxypropyl methylcellulose (HPMC).
- To enable pharmaceutical manufacturers to assess excipient quality and mitigate nitrosamine risks.
Main Methods:
- Development of a two-dimensional ion chromatography mass spectrometry (2D-IC/MS) method using heart-cutting mode.
- Utilized a concentrator column, anion-exchange columns (1D and 2D), and mass spectrometry detection with an isotope-labeled internal standard.
- Implemented a novel cleaning procedure for labware to eliminate nitrite contamination.
Main Results:
- The 2D-IC/MS method achieved high sensitivity and specificity for trace nitrite detection in HPMC.
- Validated linearity (R² > 0.9999), precision (RSD 3.5-10.1%), and recovery (90.5-102.4%).
- Achieved a limit of detection of 8.9 ng/g and limit of quantitation of 29.6 ng/g in HPMC.
Conclusions:
- The developed 2D-IC/MS method is suitable for sensitive and accurate trace nitrite determination in pharmaceutical excipients.
- This method supports the pharmaceutical industry in controlling nitrosamine impurities and ensuring drug product safety.
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