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Determination of carbidopa, 3-O-methyldopa, levodopa, benserazide and dopamine in plasma samples from Parkinsonian patients by SALLE / HILIC-MS / MS method

Grant number: 17/26697-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2018
Effective date (End): December 31, 2018
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
Principal Investigator:Maria Eugênia Queiroz Nassur
Grantee:Lídia Miranda da Silva
Home Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:17/02147-0 - Single drop chromatography and its coupling to mass spectrometry: instrumental strategies, development of materials, automation and analytical applications, AP.TEM

Abstract

Parkinson's disease (PD) is characterized by chronic and progressive degeneration of the motor system, presenting as classic symptom tremor in the upper limbs. This progressive neurodegenerative disease is caused by the degeneration of the dopaminergic neurons of the nigrostriatal system, affecting the motor system. The PD has been treated with levodopa (LD), a drug capable of effectively improving the symptoms of the initial phase of this syndrome. This drug is converted to dopamine by the enzyme dopamine decarboxylase, which is present in the central and peripheral nervous system. LD when associated with peripheral dopa decarboxylase inhibitors such as carbidopa or benserazide increases the availability (LD) in the central nervous system and decreases the adverse effects of dopamine in the peripheral system. In the advanced phase of this syndrome adjustments of the doses of LD and the peripheral dopamine decarboxylase inhibitor drugs are necessary, since the degeneration of the nigrostriatal cells is observed. In this project, salting-out assisted liquid/liquid extraction (SALLE) and liquid chromatography with hydrophilic interaction coupled to Tandem mass spectrometry (HILIC-MS / MS) will be optimized and validated for the determination of carbidopa, levodopa, dopamine, 3-O-methyl-dopa and benserazide in plasma samples of patients with PD. Plasma concentrations of levodopa, 3-O-methyl-dopa, peripheral dopamine decarboxylase (carbidopa and benserazide) and dopamine inhibitor drugs will be determined in patients with Parkinson's disease on prolonged treatment with levodopa / carbidopa or levodopa / benserazide with symptoms of motor fluctuations (wearing-off) and dyskinesias. This study will aid in adjusting the doses of these patients.