Cargando…

Development and Validation of a New LC-MS/MS Bioanalytical Method for the Simultaneous Determination of Levodopa, Levodopa Methyl Ester, and Carbidopa in Human Plasma Samples

Levodopa (L-DOPA) treatment, combined with the administration of dopa-decarboxylase inhibitors (DDCIs), is still the most effective symptomatic treatment of Parkinson’s disease (PD). Although its efficacy in the early stage of the disease has been confirmed, its complex pharmacokinetics (PK) increas...

Descripción completa

Detalles Bibliográficos
Autores principales: Molteni, Linda, Charlier, Bruno, Izzo, Viviana, Coglianese, Albino, Conti, Valeria, Eleopra, Roberto, Cilia, Roberto, Capelli, Chiara, D’Urso, Annachiara, de Grazia, Ugo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254897/
https://www.ncbi.nlm.nih.gov/pubmed/37298741
http://dx.doi.org/10.3390/molecules28114264
_version_ 1785056750296104960
author Molteni, Linda
Charlier, Bruno
Izzo, Viviana
Coglianese, Albino
Conti, Valeria
Eleopra, Roberto
Cilia, Roberto
Capelli, Chiara
D’Urso, Annachiara
de Grazia, Ugo
author_facet Molteni, Linda
Charlier, Bruno
Izzo, Viviana
Coglianese, Albino
Conti, Valeria
Eleopra, Roberto
Cilia, Roberto
Capelli, Chiara
D’Urso, Annachiara
de Grazia, Ugo
author_sort Molteni, Linda
collection PubMed
description Levodopa (L-DOPA) treatment, combined with the administration of dopa-decarboxylase inhibitors (DDCIs), is still the most effective symptomatic treatment of Parkinson’s disease (PD). Although its efficacy in the early stage of the disease has been confirmed, its complex pharmacokinetics (PK) increases the variability of the intra-individual motor response, thus amplifying the risk of motor/non-motor fluctuations and dyskinesia. Moreover, it has been demonstrated that L-DOPA PK is strongly influenced by several clinical, therapeutic, and lifestyle variables (e.g., dietary proteins). L-DOPA therapeutic monitoring is therefore crucial to provide personalized therapy, hence improving drug efficacy and safety. To this aim, we have developed and validated an ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) method to quantify L-DOPA, levodopa methyl ester (LDME), and the DDCI carbidopa in human plasma. The compounds were extracted by protein precipitation and samples were analyzed with a triple quadrupole mass spectrometer. The method showed good selectivity and specificity for all compounds. No carryover was observed, and dilution integrity was demonstrated. No matrix effect could be retrieved; intra-day and inter-day precision and accuracy values met the acceptance criteria. Reinjection reproducibility was assessed. The described method was successfully applied to a 45-year-old male patient to compare the pharmacokinetic behavior of an L-DOPA-based medical treatment involving commercially available Mucuna pruriens extracts and an LDME/carbidopa (100/25 mg) formulation.
format Online
Article
Text
id pubmed-10254897
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-102548972023-06-10 Development and Validation of a New LC-MS/MS Bioanalytical Method for the Simultaneous Determination of Levodopa, Levodopa Methyl Ester, and Carbidopa in Human Plasma Samples Molteni, Linda Charlier, Bruno Izzo, Viviana Coglianese, Albino Conti, Valeria Eleopra, Roberto Cilia, Roberto Capelli, Chiara D’Urso, Annachiara de Grazia, Ugo Molecules Article Levodopa (L-DOPA) treatment, combined with the administration of dopa-decarboxylase inhibitors (DDCIs), is still the most effective symptomatic treatment of Parkinson’s disease (PD). Although its efficacy in the early stage of the disease has been confirmed, its complex pharmacokinetics (PK) increases the variability of the intra-individual motor response, thus amplifying the risk of motor/non-motor fluctuations and dyskinesia. Moreover, it has been demonstrated that L-DOPA PK is strongly influenced by several clinical, therapeutic, and lifestyle variables (e.g., dietary proteins). L-DOPA therapeutic monitoring is therefore crucial to provide personalized therapy, hence improving drug efficacy and safety. To this aim, we have developed and validated an ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) method to quantify L-DOPA, levodopa methyl ester (LDME), and the DDCI carbidopa in human plasma. The compounds were extracted by protein precipitation and samples were analyzed with a triple quadrupole mass spectrometer. The method showed good selectivity and specificity for all compounds. No carryover was observed, and dilution integrity was demonstrated. No matrix effect could be retrieved; intra-day and inter-day precision and accuracy values met the acceptance criteria. Reinjection reproducibility was assessed. The described method was successfully applied to a 45-year-old male patient to compare the pharmacokinetic behavior of an L-DOPA-based medical treatment involving commercially available Mucuna pruriens extracts and an LDME/carbidopa (100/25 mg) formulation. MDPI 2023-05-23 /pmc/articles/PMC10254897/ /pubmed/37298741 http://dx.doi.org/10.3390/molecules28114264 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Molteni, Linda
Charlier, Bruno
Izzo, Viviana
Coglianese, Albino
Conti, Valeria
Eleopra, Roberto
Cilia, Roberto
Capelli, Chiara
D’Urso, Annachiara
de Grazia, Ugo
Development and Validation of a New LC-MS/MS Bioanalytical Method for the Simultaneous Determination of Levodopa, Levodopa Methyl Ester, and Carbidopa in Human Plasma Samples
title Development and Validation of a New LC-MS/MS Bioanalytical Method for the Simultaneous Determination of Levodopa, Levodopa Methyl Ester, and Carbidopa in Human Plasma Samples
title_full Development and Validation of a New LC-MS/MS Bioanalytical Method for the Simultaneous Determination of Levodopa, Levodopa Methyl Ester, and Carbidopa in Human Plasma Samples
title_fullStr Development and Validation of a New LC-MS/MS Bioanalytical Method for the Simultaneous Determination of Levodopa, Levodopa Methyl Ester, and Carbidopa in Human Plasma Samples
title_full_unstemmed Development and Validation of a New LC-MS/MS Bioanalytical Method for the Simultaneous Determination of Levodopa, Levodopa Methyl Ester, and Carbidopa in Human Plasma Samples
title_short Development and Validation of a New LC-MS/MS Bioanalytical Method for the Simultaneous Determination of Levodopa, Levodopa Methyl Ester, and Carbidopa in Human Plasma Samples
title_sort development and validation of a new lc-ms/ms bioanalytical method for the simultaneous determination of levodopa, levodopa methyl ester, and carbidopa in human plasma samples
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254897/
https://www.ncbi.nlm.nih.gov/pubmed/37298741
http://dx.doi.org/10.3390/molecules28114264
work_keys_str_mv AT moltenilinda developmentandvalidationofanewlcmsmsbioanalyticalmethodforthesimultaneousdeterminationoflevodopalevodopamethylesterandcarbidopainhumanplasmasamples
AT charlierbruno developmentandvalidationofanewlcmsmsbioanalyticalmethodforthesimultaneousdeterminationoflevodopalevodopamethylesterandcarbidopainhumanplasmasamples
AT izzoviviana developmentandvalidationofanewlcmsmsbioanalyticalmethodforthesimultaneousdeterminationoflevodopalevodopamethylesterandcarbidopainhumanplasmasamples
AT coglianesealbino developmentandvalidationofanewlcmsmsbioanalyticalmethodforthesimultaneousdeterminationoflevodopalevodopamethylesterandcarbidopainhumanplasmasamples
AT contivaleria developmentandvalidationofanewlcmsmsbioanalyticalmethodforthesimultaneousdeterminationoflevodopalevodopamethylesterandcarbidopainhumanplasmasamples
AT eleopraroberto developmentandvalidationofanewlcmsmsbioanalyticalmethodforthesimultaneousdeterminationoflevodopalevodopamethylesterandcarbidopainhumanplasmasamples
AT ciliaroberto developmentandvalidationofanewlcmsmsbioanalyticalmethodforthesimultaneousdeterminationoflevodopalevodopamethylesterandcarbidopainhumanplasmasamples
AT capellichiara developmentandvalidationofanewlcmsmsbioanalyticalmethodforthesimultaneousdeterminationoflevodopalevodopamethylesterandcarbidopainhumanplasmasamples
AT dursoannachiara developmentandvalidationofanewlcmsmsbioanalyticalmethodforthesimultaneousdeterminationoflevodopalevodopamethylesterandcarbidopainhumanplasmasamples
AT degraziaugo developmentandvalidationofanewlcmsmsbioanalyticalmethodforthesimultaneousdeterminationoflevodopalevodopamethylesterandcarbidopainhumanplasmasamples