An update on the current status and prospects of nitrosation pathways and possible root causes of nitrosamine formation in various pharmaceuticals.

Over the last two years, global regulatory authorities have raised safety concerns on nitrosamine contamination in several drug classes, including angiotensin II receptor antagonists, histamine-2 receptor antagonists, antimicrobial agents, and antidiabetic drugs. To avoid carcinogenic and mutagenic effects in patients relying on these medications, authorities have established specific guidelines in risk assessment scenarios and proposed control limits for nitrosamine impurities in pharmaceuticals. In this review, nitrosation pathways and possible root causes of nitrosamine formation in pharmaceuticals are discussed.

Current status and prospects of development of analytical methods for determining nitrosamine and N-nitroso impurities in pharmaceuticals.

Nitrosamine impurities in pharmaceuticals have recently been concerned for several national regulatory agencies to avoid carcinogenic and mutagenic effects in patients. The demand for highly sensitive and specific analytical methods with LOQs in the ppb and sub-ppb ranges is among the most significant challenges facing analytical scientists. In addition, artifactual nitrosamine formation during sample preparation and injection leading to overestimation of nitrosamines has received considerable attention.