Angiotensin-receptor blockers (ARBs) or sartans are among the most widely used medicines for hypertension and heart failure. A lot of commotion has been raised over the problem of successive global recalls of several generic preparations of ARBs. Carcinogenic nitrosamine impurities namely NDMA, NDEA and NMBA, are detected initially in valsartan products by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) while other authorities followed closely with similar recalls.
The quality concern rises over valsartan crisis resulted in FDA scientists developing novel and sophisticated testing methods specifically designed to detect additional emerging nitrosamine impurities. One of the methods the Office of Testing and Research from FDA has developed is based on a gas chromatography-mass spectrometry (GC-MS) headspace method. The Thermo Scientific application note, Determination of Genotoxic Nitrosamines in Valsartan with Gas Chromatography and Mass Spectrometry, demonstrates the quantitative performance of Thermo Scientific™ GC-MS solutions in combination with liquid and headspace sampling techniques to determine genotoxic nitrosamines in valsartan. The results presented are compliant with the FDA standard methods for nitrosamines detection and quantification in valsartan, providing excellent flexibility and analytical performance for routine laboratory use.
Another FDA method is based on a single HRAM LC-MS method using either the Thermo ScientificTM Q ExactiveTM Hybrid Quadrupole-OrbitrapTM Mass Spectrometer or the Q ExactiveTM HF-X hybrid Quadrupole-OrbitrapTM Mass Spectrometer, which is capable of quantifying all of the six nitrosamine impurities namely NDMA, NDEA, NEIPA, NDIPA, NDBA and NMBA simultaneously.
Thermo Fisher Scientific is one of the leading manufacturers of mass spectrometry instruments and has optimized and validated these FDA methods on Thermo Scientific GCMS and LCMS systems. These analyses meet all the requirements of current regulations, sensitivity and repeatability exceeding the expected requirements of the control limits.
