N-nitrosodimethylamine (NDMA) has been classified by the International Agency for Research on Cancer (IARC) as a probable human carcinogen even at low exposure levels. Therefore, regulatory agencies, European Medicines Agency (EMA) and U.S. Food and Drugs Administration (FDA) have been closely monitoring the levels of nitrosamine impurities to ensure medicinal products are of acceptable quality and are safe for patients to consume.
A year after the quality concerns over the valsartan crisis in 2018, the pesky NMDA is now causing problems in ranitidine. In 2019, FDA announced that low levels of NDMA was found in samples of some ranitidine medicine, an over-the-counter (OTC) and a H2 (histamine-2) blocker prescription drug, which relieves heartburn by decreasing the amount of acid created by the stomach. This resulted in FDA releasing testing methods to provide options for regulators and industry to detect nitrosamine impurities in ranitidine drug substance and drug product.
In GC-MS testing methods for nitrosamines impurities in ranitidine, N-nitroso-N-methyl-4-aminobutyric acid (NMBA) cannot be directly detected in certain angiotensin II receptor blocker (ARB) drug products. Thus, FDA developed and validated a single HRAM LC-MS method following ICH Q2(R1) that can quantify all six nitrosamine impurities simultaneously. The FDA method utilizes the exceptional acquisition speed, sensitivity, and resolving power of the Thermo ScientificTM Q ExactiveTM Hybrid Quadrupole-OrbitrapTM Mass Spectrometer or Q ExactiveTM HF-X Hybrid Quadrupole-OrbitrapTM Mass Spectrometer system for the determination of these trace level genotoxic impurities.
Q Exactive™ Hybrid Quadrupole-Orbitrap™ Mass Spectrometer
Identify, quantify and confirm more compounds rapidly and with confidence using the Thermo Scientific™ Q Exactive™ Hybrid Quadrupole-Orbitrap Mass Spectrometer. This benchtop LC-MS/MS system combines quadruple precursor ion selection with high-resolution, accurate-mass (HRAM) Orbitrap detection to deliver exceptional performance and versatility. The Q Exactive Mass Spectrometer is equally useful for untargeted or targeted screening and a broad range of qualitative and quantitative applications in drug discovery, proteomics, environmental and food safety, clinical research and forensic toxicology.
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