Recent Analytical Methods for N-Nitrosamine Analysis as Impurities in Drug Substances and Drug Products.
- 1Department of Pharmaceutical Analysis and Medicinal Chemistry Faculty of Pharmacy Universitas Padjadjaran Sumedang 45363 Indonesia unpad.ac.id.
- 2Undergraduate Program of Pharmacy Faculty of Pharmacy Universitas Padjadjaran Sumedang 45363 Indonesia unpad.ac.id.
Abstract
N-nitrosamine (hereinafter nitrosamine) is among the organic impurities characterized by high potency as genotoxic and probable human carcinogens found in drug substances and drug products. This type of impurity has become a major concern in pharmaceutical industry, since one of nitrosamine type of impurities, NDMA, was detected in valsartan active pharmaceutical ingredients back in 2018. As a result, the development of sensitive, selective, and reliable analytical methods is essential to maintain regulatory compliance and safeguard of patient health. This review provides an overview of recent analytical strategies in 2020-2025 for detecting nitrosamine impurities in pharmaceutical substances and products, with an emphasis on chromatography-based techniques and groundbreaking analytical approaches. Gas chromatography (GC) and liquid chromatography (LC) coupled with mass spectrometry are the predominant methods, offering high sensitivity and selectivity for quantifying trace levels of these impurities. GC-based techniques are most appropriate for volatile and thermally stable nitrosamines, whereas LC-MS methods are suitable for polar, nonvolatile, thermally unstable, and structurally complex nitrosamines, including nitrosamine drug substance-related impurities (NDSRIs). Additionally, alternative LC-based detectors, such as ultraviolet (UV) and fluorescence detection (FLD), as well as total nitrosamine assays, chemiluminescence, and colorimetric methods, are evaluated as complementary or cost-effective analytical options. Key analytical considerations, including sample preparation, ionization techniques, matrix effects, derivatization strategies, and method validation, are also examined. Furthermore, this review highlights current challenges and future directions in nitrosamine analysis.
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BibTeX
@article{pratiwi2026recent,
title = {{Recent Analytical Methods for N-Nitrosamine Analysis as Impurities in Drug Substances and Drug Products.}},
author = {Rimadani Pratiwi and Alifa Dhia Shalima and Mutakin and Aliya Nur Hasanah},
journal = {Journal of analytical methods in chemistry},
year = {2026},
month = oct,
doi = {10.1155/jamc/9550913},
url = {https://europepmc.org/article/MED/42923503},
note = {CC BY},
}
RIS
TY - JOUR
TI - Recent Analytical Methods for N-Nitrosamine Analysis as Impurities in Drug Substances and Drug Products.
AU - Rimadani Pratiwi
AU - Alifa Dhia Shalima
AU - Mutakin
AU - Aliya Nur Hasanah
PY - 2026
DA - 2026/10/22
JO - Journal of analytical methods in chemistry
DO - 10.1155/jamc/9550913
UR - https://europepmc.org/article/MED/42923503
AB - N-nitrosamine (hereinafter nitrosamine) is among the organic impurities characterized by high potency as genotoxic and probable human carcinogens found in drug substances and drug products. This type of impurity has become a major concern in pharmaceutical industry, since one of nitrosamine type of impurities, NDMA, was detected in valsartan active pharmaceutical ingredients back in 2018. As a result, the development of sensitive, selective, and reliable analytical methods is essential to maintain regulatory compliance and safeguard of patient health. This review provides an overview of recent analytical strategies in 2020-2025 for detecting nitrosamine impurities in pharmaceutical substances and products, with an emphasis on chromatography-based techniques and groundbreaking analytical approaches. Gas chromatography (GC) and liquid chromatography (LC) coupled with mass spectrometry are the predominant methods, offering high sensitivity and selectivity for quantifying trace levels of these impurities. GC-based techniques are most appropriate for volatile and thermally stable nitrosamines, whereas LC-MS methods are suitable for polar, nonvolatile, thermally unstable, and structurally complex nitrosamines, including nitrosamine drug substance-related impurities (NDSRIs). Additionally, alternative LC-based detectors, such as ultraviolet (UV) and fluorescence detection (FLD), as well as total nitrosamine assays, chemiluminescence, and colorimetric methods, are evaluated as complementary or cost-effective analytical options. Key analytical considerations, including sample preparation, ionization techniques, matrix effects, derivatization strategies, and method validation, are also examined. Furthermore, this review highlights current challenges and future directions in nitrosamine analysis.
SN - 2090-8865
SN - 2090-8873
ER -