Abstract
Pimavanserin is an atypical antipsychotic indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. As it is a relatively new drug on the market, limited number of pharmacokinetic information and analytical methods are available. This paper presents an ultra-high performance chromatography for the simultaneous determination of pimavanserin and its four process impurities. The method was developed applying analytical quality by design (AQbD) principles as a risk-based approach. Critical method attributes (CMAs) were selected as a resolution between the worst separated compounds (impurity B and impurity C), a duration of analysis defined by the retention time of the last eluting peak (impurity D), a capacity factor of the first eluted impurity (impurity A), a tailing factor and a theoretical plate number. Risk assessment in the early stage of method development pointed out critical method parameters (CMPs): column temperature, gradient time and pH-value of the mobile phase (water phase, eluent A). Design of experiments (DoE), using DryLab®4 software, was applied to evaluate the influence of CMPs on CMAs and to determine method operable design region (MODR). Based on the risk assess...Continue Reading
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