DETECTING LOW-LEVEL IMPURITIES

Abstract

IN THE FAIRY TALE, a supposed princess detects a single pea hidden under a pile of 20 featherbeds and 20 mattresses. Her remarkable pea-per-mattress sensitivity proves her royal identity. In the real world, analytical chemists are akin to suspicious royals in the tale, looking for highly sensitive measures to prove a truth. Since 2007, guidelines from the European Medicines Agency and a draft version from the U.S. Food & Drug Administration have called on the drug industry to reduce DNA-reactive genotoxic impurities (GTIs) in pharmaceuticals. The EMA guidelines suggest only that GTIs should be detected and quantified by “state-of-the-art analytical techniques.” But the result has been a paradigm shift in pharmaceutical impurity profiling and control, says Fenghe Qiu, leader of the trace analysis group at drugmaker Boehringer Ingelheim. Although the guidelines broadly affect process chemistry and drug development work (see page 16), the analytical science groups at pharmaceutical companies have been hit ha...