A Full Evaporation Static Headspace Gas Chromatography Method with Nitrogen Phosphorous Detection for Ultrasensitive Analysis of Semi-volatile Nitrosamines in Pharmaceutical Products

The recent detection of potent carcinogenic nitrosamine impurities in several human medicines has triggered product recalls and interrupted the supply of critical medications for hundreds of millions of patients, illuminating the need for increased testing of nitrosamines in pharmaceutical products....

Full description

Saved in:
Bibliographic Details
Published in:The AAPS journal 2022-01, Vol.24 (1), p.23-23, Article 23
Main Authors: Zheng, Jinjian, Kirkpatrick, Christine L., Lee, Daniel, Han, Xinxin, Martinez, Ana I., Gallagher, Kimberly, Evans, Rebecca K., Mudur, Sanjay V., Liang, Xihui, Drake, Jennifer, Buhler, Leah A., Mowery, Mark D.
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedicine
Biotechnology
Chromatography, Gas - methods
Chromatography, Liquid - methods
Dimethylnitrosamine - analysis
Drug Contamination - prevention & control
Gas chromatography
Limit of Detection
Mass Spectrometry - methods
Methods
Nitrogen
Nitrosamines - analysis
Nitrosoamines
Pharmaceutical Preparations - analysis
Pharmaceutical Preparations - chemistry
Pharmacology/Toxicology
Pharmacy
Phosphates
Reproducibility of Results
Research Article
Valsartan
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The recent detection of potent carcinogenic nitrosamine impurities in several human medicines has triggered product recalls and interrupted the supply of critical medications for hundreds of millions of patients, illuminating the need for increased testing of nitrosamines in pharmaceutical products. However, the development of analytical methods for nitrosamine detection is challenging due to high sensitivity requirements, complex matrices, and the large number and variety of samples requiring testing. Herein, we report an analytical method for the analysis of a common nitrosamine, N-nitrosodimethylamine (NDMA), in pharmaceutical products using full evaporation static headspace gas chromatography with nitrogen phosphorous detection (FE-SHSGC-NPD). This method is sensitive, specific, accurate, and precise and has the potential to serve as a universal method for testing all semi-volatile nitrosamines across different drug products. Through elimination of the detrimental headspace-liquid partition, a quantitation limit of 0.25 ppb is achieved for NDMA, a significant improvement upon traditional LC-MS methods. The extraction of nitrosamines directly from solid sample not only simplifies the sample preparation procedure but also enables the method to be used for different products as is or with minor modifications, as demonstrated by the analysis of NDMA in 10+ pharmaceutical products. The in situ nitrosation that is commonly observed in GC methods for nitrosamine analysis was completely inhibited by the addition of a small volume solvent containing pyrogallol, phosphoric acid, and isopropanol. Employing simple procedures and low-cost instrumentation, this method can be implemented in any analytical laboratory for routine nitrosamine analysis, ensuring patient safety and uninterrupted supply of critical medications. Graphical Abstract
ISSN:1550-7416
1550-7416
DOI:10.1208/s12248-021-00669-8