DEGRADATION STUDYOF PIMAVANSERIN: IDENTIFICATION, ISOLATION AND STRUCTURAL CHARACTERIZATION OF DEGRADANTS

Pimavanserin (PMV) is a novel antipsychotic drug that is used for the treatment of Parkinson's disease and psychosis. PMV stability is characterized by subjecting it to systematic forced degradation in various stress conditions such as acid, base, peroxide, UV-light and heat as per ICH guidelines. Three PMV degradants were identified, one each from acid, base and peroxide catalysed degradation. All the three PMV degradants were isolated on C18 column by using preparative HPLC with gradient elution method and labelled as DP-1, DP-2 and DP-3, and their structures were elucidated by mass and 2D NMR spectral analysis. DP-1 was identified as bis (4isobutoxyphenyl) methane, DP-2 was identified as1,3-bis(4-isobutoxybenzyl)urea and DP-3 was identified as Noxide product of PMV. Interestingly, both acid and base degradation products of PMV (DP-1 and DP-2) contain Iso butoxy benzyl amine portion of the drug which is stable, and the remaining fragment of PMV is sensitive to stress. PMV degradation products, DP-1 and DP-2 were confirmed as dimers, and DP-3 as N-oxide product resulting from the peroxide mediated oxidation. Furthermore, PMV was found to be stable for 48 hrs when exposed to UV-light and subjected to 70 °C.