Electrochemistry of the COMT Enzyme Inhibitor Entacapone and Its Determination in Pharmaceutical Formulation and Human Blood-Pharmacokinetic Study

Entacapone (ENT) is a potent inhibitor of catechol-O-methyltransferase enzyme. ENT is reduced via two irreversible cathodic waves over the pH range 2.0-11.5. It has strong interfacial adsorptive behavior onto Hg electrode surface. Langmuir isotherm indicated monolayer adsorption and the equilibrium parameter RL value (0.40 - 0.93) indicated that sorption process was favorable. A monolayer surface coverage of 6.06 × 10−10 mol cm−2 was estimated and each adsorbed ENT molecule occupied an area of 0.27 nm2. Taking advantage of the adsorption features of ENT, a sensitive and selective square-wave adsorptive cathodic stripping voltammetric (SW-AdCSV) method was developed for trace determination of ENT in pure form, commercial formulations (in Comtan tablets; as a single active drug and in Stalevo 200 tablets; as tertiary mixture of ENT, levodopa and carbidopa) and in human serum. Limits of quantification (LOQ) of 5.0 × 10−10 and 1.3 × 10−9 mol L−1 ENT were achieved in pure form and in spiked human serum, respectively. This analysis was carried out without addition of any surfactant, extraction of the drug and interference from some common excipients, co-formulated and co-administrated drugs. The proposed method has also been successfully applied for assay of ENT in real plasma samples and seems to be suitable for therapeutic drug monitoring purposes.