Determination of the catechol-O-methyltransferase inhibitor tolcapone and three of its metabolites in animal and human plasma and urine by reversed-phase high-performance liquid chromatography with ultraviolet detection

Heizmann, P.; Schmitt, Monique; Leube, Joachim; Martin, Helmut; Saner, A.

doi:10.1016/s0378-4347(99)00146-2

Cited by 5 publications

(6 citation statements)

References 3 publications

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“…The conjugate positions we shown in Fig. 1 are the most probable conjugated positions based on previous tolcapone drug metabolite studies [14][15][16]. The conjugated positions would have to be verified by conjugated standards and/or by isolation with additional NMR analyses.…”

Section: Discussionmentioning

confidence: 90%

See 1 more Smart Citation

Identification of metabolite profiles of the catechol-O-methyl transferase inhibitor tolcapone in rat urine using LC/MS-based metabonomics analysis

Sun¹,

Tungeln²,

Hines³

et al. 2009

Journal of Chromatography B

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Section: Discussionmentioning

confidence: 90%

“…A number of studies [14][15][16] have been conducted on the pharmacokinetics of tolcapone. Jorga et al [14] have reported that four primary metabolic pathways for tolcapone include glucuronida- tion, methylation, oxidative hydroxylation and reduction reactions.…”

Section: Tolcaponementioning

confidence: 99%

Identification of metabolite profiles of the catechol-O-methyl transferase inhibitor tolcapone in rat urine using LC/MS-based metabonomics analysis

Sun¹,

Tungeln²,

Hines³

et al. 2009

Journal of Chromatography B

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“…Plasma concentrations of tolcapone and its methylated derivative 3‐ O ‐methyltolcapone (3‐OMT, Ro 40–7591); were measured in all samples by reverse‐phase h.p.l.c. with ultraviolet detection as described elsewhere [ 10, 11]. The LOQ was 0.05 μg ml −1 for both compounds.…”

Section: Methodsmentioning

confidence: 99%

Metabolism and excretion of tolcapone, a novel inhibitor of catechol‐O‐methyltransferase

Jorga

Fotteler

Heizmann

et al. 1999

Brit J Clinical Pharma

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Aims To investigate the rate of excretion and routes of metabolism of tolcapone, a novel inhibitor of catechol-O-methyltransferase (COMT). Methods Six healthy male volunteers were given 200 mg [14 C]-tolcapone (approximately 50 mCi) orally. To assess excretion balance and to identify metabolites, urine and faeces were collected before administration and until radioactivity fell below 75 d min −1 ml −1 (urine) and 100 d min −1 mg −1 (faeces). Blood samples were collected frequently before and after administration to determine plasma radioactivity, to identify tolcapone metabolites and to measure plasma tolcapone and its methylated derivative 3-O-methyltolcapone (3-OMT).Results The mean proportion of the dose excreted in urine was 57.3% and in faeces 40.5%. Excretion was almost complete (more than 95%) in all participants after 9 days. The major early metabolite present in plasma was the 3-O-b,d-glucuronide conjugate, which was detectable within 2 h after dosing. The major late metabolite in plasma was 3-OMT. The 3-O-b,d-glucuronide was also the most abundant metabolite in urine and faeces, accounting for 27% and 33%, respectively, of the total radioactivity excreted by these routes and for 26% of the original dose. Reduction of the nitro moiety yields an amine derivative, detected in both urine and faeces, with subsequent modifications, such as acetylation of the amine group and conjugation with glucuronic acid or sulphate, or both. Oxidative reactions due to cytochrome P450 enzymes are of small significance, as is 3-O-methylation by COMT. Conclusions Tolcapone is almost completely metabolized and excreted in urine and faeces (only 0.5% of tolcapone was excreted unchanged); glucuronidation is the most important route of metabolism. The relatively long duration of excretion is caused by the long half-life of 3-OMT.

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“…In terms of sensitivity, the developed method showed limits of detection similar to those obtained with an electrochemical detector [4,7,8,[14][15][16][17][18][19][20] and was also twice as sensitive as coulometric [4] and UV detectors [21]. Compared with other HPLC-MS methods, the new method also showed significantly lower limits of quantification for most compounds [23][24][25][26].…”

Section: Methods Optimizationmentioning

confidence: 53%

“…To meet this requirement, several bioanalytical methods based on HPLC have been described in the literature. Most of these methods involve the use of electrochemical [4,7,8,[14][15][16][17][18][19][20], UV [21] and fluorescence detectors [22], systems that promote analysis with moderate sensitivity and selectivity in biological matrices. The use of HPLC-MS/MS offers numerous advantages over that of other techniques, especially the ability to analyze multiple compounds with high sensitivity and selectivity.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Determination of Levodopa, Carbidopa, Entacapone, Tolcapone, 3- O -Methyldopa and Dopamine in Human Plasma by an Hplc–MS/MS Method

et al. 2015

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Determination of the catechol-O-methyltransferase inhibitor tolcapone and three of its metabolites in animal and human plasma and urine by reversed-phase high-performance liquid chromatography with ultraviolet detection

Cited by 5 publications

References 3 publications

Identification of metabolite profiles of the catechol-O-methyl transferase inhibitor tolcapone in rat urine using LC/MS-based metabonomics analysis

Identification of metabolite profiles of the catechol-O-methyl transferase inhibitor tolcapone in rat urine using LC/MS-based metabonomics analysis

Metabolism and excretion of tolcapone, a novel inhibitor of catechol‐O‐methyltransferase

Simultaneous Determination of Levodopa, Carbidopa, Entacapone, Tolcapone, 3- O -Methyldopa and Dopamine in Human Plasma by an Hplc–MS/MS Method

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