Application Note ReView: AS239 – Full Method Validation of an Automated Solution for Nitrosamines in Irbesartan and Metformin by LC-MS-MS Analysis
Following the discovery of nitrosamines contamination in certain classes of drug products in recent years, regulators have mandated worldwide stringent reviews of the pharmaceutical industry portfolio, including challenging analytical testing to meet the recently established zero-risk environment requirements. Therefore, in this edition of Application Note ReView we take a look back at AS239 – Full Method Validation of an Automated Solution for Nitrosamines in Irbesartan and Metformin by LC-MS-MS Analysis.
This application note follows the preliminary work undertaken at Anatune to address the measurement of a wide range of nitrosamines in drug substance as outlined in Application Note AS234.
Initial evaluation highlighted the significant benefits of a fully automated solution for this analytical challenge, specifically to reduce risks of contamination and the occurrence of false positives. Automation of sample preparation can help significantly in addressing some of the many challenges to be faced in the analysis of nitrosamines thanks to its inherent qualities of convenience, control, and consistency.
Here we demonstrate the optimisation and validation of a fully automated solution for the sample preparation and LC-MS-MS analysis of seven target nitrosamines in two classes of drug substance, Irbesartan (angiotensin II receptor antagonist) and Metformin (biguanide analogue antidiabetic).
The inherent benefits of automated sample preparation, including convenience, reduced environmental exposure, and improved accuracy and precision are clearly demonstrated, alongside the significant benefit of high throughput unattended operation.
This solution will be of interest to pharmaceutical drug substance and drug product manufacturers to support their research, process development and quality control programs. CRO organisations offering outsourced, high throughput, testing will also benefit greatly from the quality and efficiency gains associated with this automated analysis.
This application note describes the optimisation and validation of a fully automated solution for the sample preparation and LCMS/MS analysis of seven target nitrosamines in two drug substances, Irbesartan and Metformin.
All figures of merit evaluated during the validation of this method met acceptance criteria for all analytes in both investigated matrices, except for NDBA, for which further work is being undertaken.
The results were presented and discussed with Mark Harrison at AstraZeneca who considered the data acceptable to pass validation for the key nitrosamines. This optimised and validated analytical solution clearly indicates the benefits of automated sample preparation for complex analyses in terms of improved analytical performance, protection from contamination and convenience.
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