title: Bioanalytical chromatographic methods for the determination of catechol-O-methyltransferase inhibitors in rodents and human samples: a review.
abstract: In the past years, it has been recognised that the levodopa therapy may be improved with therapeutic regimens including a catechol-O-methyltransferase (COMT) inhibitor. At the present time, tolcapone and entacapone are the only two COMT inhibitors available in the market. However, further COMT inhibitors are under development for Parkinson's disease, namely nebicapone and opicapone (formerly known as BIA 9-1067). In addition, the nitecapone, another well-known COMT inhibitor, is also in preclinical development but for neuropathic pain. Since the 1990s different liquid chromatography methods have been developed and validated to quantify tolcapone, entacapone, nitecapone, nebicapone and some metabolites in biological samples, particularly in plasma samples obtained from rodent and human species. These bioanalytical methods have been primarily used to support pharmacokinetic assays with such COMT inhibitors in non-clinical and clinical studies. As these inhibitors present hydrophobic groups in their chemical structures, reversed-phase liquid chromatography has been used as the major approach for the determination of such compounds, especially high-performance liquid chromatography coupled to ultraviolet detection (HPLC-UV), electrochemical detection (HPLC-ECD) and mass spectrometry detection (HPLC-MS). Regarding the sample preparation, the traditional liquid-liquid extraction (LLE) and solid-phase extraction (SPE) were also the most widely used procedures for extraction of the analytes of interest prior to the analysis of samples. Thus, this review aimed to gather, for the first time, sufficient background information about the bioanalytical chromatographic methods which have been already developed and applied for the determination of tolcapone, entacapone, nitecapone, nebicapone and their metabolites. Moreover, some pharmacokinetic aspects of the COMT inhibitors with interest from a bioanalytical perspective were also addressed.
authors: Department of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, Coimbra, Portugal.
authors: Daniela
authors: D
authors: Gonçalves
authors: Gilberto
authors: G
authors: Alves
authors: Patrício
authors: P
authors: Soares-da-Silva
authors: Amílcar
authors: A
authors: Falcão
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000032:analysis* / Q000378:metabolism / Q000627:therapeutic use; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D002851:Chromatography, High Pressure Liquid; D055664:Electrochemical Techniques; D004791:Enzyme Inhibitors / Q000032:analysis* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D013058:Mass Spectrometry; D010300:Parkinson Disease / Q000188:drug therapy / Q000201:enzymology
chemical_list: D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors; D002394:Catechol O-Methyltransferase