**3.5.4 Tremogenic impurities**

Tremogenic impurities comprise another sub-class of highly toxic impurities in APIs. Two pharmacopoeial APIs are known to have the potential to be contaminated with tremogenic impurities; pethidine and paroxetine (3-[(1, 3-benzodioxol-5-yloxy) methyl]-4-(4 fluorophenyl) piperidine). Pethidine can contain trace amounts of 1-methyl-4- phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) derived from the hydrolytic degradation of side chain. 4-(4- Fluorophenyl)-1-methyl-1,2,3,6-tetrahydropyridine (FMTP) can be a potential reactant/intermediate in the synthesis of paroxetine. Owing to their toxicity to cells in the *Substantia nigra*, these highly potent impurities can induce Parkinsonism in humans. Thus, these compounds are known toxic impurities; however their genotoxicity remains unclear (Borman *et al.*, 2008).
