An HPLC method for the indirect quantification of a quinone adduct of the drug paroxetine.

An HPLC method has been developed which enables the quantification of low levels of a catechol derivative and a quinone adduct of paroxetine in the presence of excess drug substance. Due to its inherent instability, the paroxetine quinone adduct is not available as a pure compound so that an indirect method was developed for its quantification. This procedure is based on the assumption that one molecule of the catechol (or more precisely the corresponding 1,2-benzoquinone) reacts with one molecule of paroxetine to produce one molecule of paroxetine quinone adduct. In the presence of paroxetine excess, pseudo-first-order kinetics was used to study the formation of the unstable product. A detector response factor for the paroxetine quinone adduct was calculated as a function of the response factor for the paroxetine catechol derivative, after considering a mass balance of the reaction. Using the methodology outlined, quantitative analysis was carried out of the paroxetine catechol derivative and the paroxetine quinone adduct in batches of paroxetine drug substance.