Development and Validation of a Sensitive LC-MS/MS Method for the Determination of N-Nitroso-Atenolol in Atenolol-Based Pharmaceuticals
The recent detection of N-nitroso-atenolol, a mutagenic and potentially carcinogenic impurity in atenolol-based pharmaceuticals, has raised serious safety concerns and emphasized the need for stringent analytical control. This study developed and validated a highly sensitive LC-MS/MS method for quan...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
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| Series: | Separations |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2297-8739/12/5/122 |
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| Summary: | The recent detection of N-nitroso-atenolol, a mutagenic and potentially carcinogenic impurity in atenolol-based pharmaceuticals, has raised serious safety concerns and emphasized the need for stringent analytical control. This study developed and validated a highly sensitive LC-MS/MS method for quantifying N-nitroso-atenolol in both active pharmaceutical ingredients (APIs) and finished products. Quantification was carried out using multiple reaction monitoring (MRM) under positive-mode electrospray ionization (ESI). Separation was performed on a C18 reversed-phase column with a gradient of water and methanol containing 0.1% formic acid. The method was validated to meet a specification limit of 15 ng/mg, with a linear range of 0.5–80 ng/mL, effectively covering 10–400% of the regulatory threshold. The method exhibited an excellent performance in terms of specificity, accuracy, precision, linearity, and robustness. It achieved a limit of detection (LOD) of 0.2 ng/mL (0.30 ng/mg) and a limit of quantification (LOQ) of 0.5 ng/mL (0.75 ng/mg), alongside a comprehensive uncertainty analysis with an expanded uncertainty of ±3.86 mg/kg. Application to commercial atenolol products confirmed the reliability and practical utility of the method. This validated approach offers a critical tool for pharmaceutical manufacturers and regulatory agencies to monitor and control N-nitroso-atenolol, ensuring compliance and enhancing patient safety. |
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| ISSN: | 2297-8739 |