Quantification of neurotransmitters in microdialysate samples following quetiapine dosing to schizophrenia phenotyped rats using a validated LC-MS/MS method

Carreño, Fernando; Helfer, Victória Etges; Staudt, Keli Jaqueline; Olivo, Laura Bem; Barreto, Fabiano; Herrmann, Ana Paula; Rates, Stela Maris Kuze; Costa, Teresa Dalla

doi:10.1016/j.jchromb.2020.122282

Cited by 6 publications

(7 citation statements)

References 30 publications

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“…Microdialysis methodology for assessing DA concentration in the brain was performed as detailed by Carreño et al 17 . Briefly, rats were anesthetized with ketamine, xylazine, and acepromazine (100, 10, and 2 mg/kg, respectively; i.p.…”

Section: Methodsmentioning

confidence: 99%

“…The quantification of DA in microdialysate samples was performed using a validated liquid chromatography–electrospray ionization–tandem mass spectrometry method 17 . Microdialysate samples were directly injected into the system without the need of an internal standard or clean‐up process.…”

Section: Methodsmentioning

confidence: 99%

“…Microdialysis methodology for assessing DA concentration in the brain was performed as detailed by Carreño et al. 17 Briefly, rats were anesthetized with ketamine, xylazine, and acepromazine (100, 10, and 2 mg/kg, respectively; i.p. ), received preemptive analgesia with ketoprofen (5 mg/kg, s.c.) and local anesthesia with lidocaine (5 mg/kg s.c.) and bupivacaine (2 mg/kg s.c.).…”

Section: Methodsmentioning

confidence: 99%

“…The quantification of DA in microdialysate samples was performed using a validated liquid chromatography–electrospray ionization–tandem mass spectrometry method. 17 Microdialysate samples were directly injected into the system without the need of an internal standard or clean‐up process. No attempt to correct for in vitro probe recovery was made in the present study given that in vitro recovery cannot be directly extrapolated to in vivo samples.…”

Section: Methodsmentioning

confidence: 99%

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Pharmacokinetic/pharmacodynamic modeling of cortical dopamine concentrations after quetiapine lipid core nanocapsules administration to schizophrenia phenotyped rats

Dias,

Carreño,

Helfer

et al. 2024

CPT Pharmacom & Syst Pharma

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Schizophrenia (SCZ) response to pharmacological treatment is highly variable. Quetiapine (QTP) administered as QTP lipid core nanocapsules (QLNC) has been shown to modulate drug delivery to the brain of SCZ phenotyped rats (SPR). In the present study, we describe the brain concentration–effect relationship after administrations of QTP as a solution or QLNC to SPR and naïve animals. A semimechanistic pharmacokinetic (PK) model describing free QTP concentrations in the brain was linked to a pharmacodynamic (PD) model to correlate the drug kinetics to changes in dopamine (DA) medial prefrontal cortex extracellular concentrations determined by intracerebral microdialysis. Different structural models were investigated to fit DA concentrations after QTP dosing, and the final model describes the synthesis, release, and elimination of DA using a pool compartment. The results show that nanoparticles increase QTP brain concentrations and DA peak after drug dosing to SPR. To the best of our knowledge, this is the first study that combines microdialysis and PK/PD modeling in a neurodevelopmental model of SCZ to investigate how a nanocarrier can modulate drug PK and PD, contributing to the development of new treatment strategies for SCZ.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacokinetic/pharmacodynamic modeling of cortical dopamine concentrations after quetiapine lipid core nanocapsules administration to schizophrenia phenotyped rats

Dias,

Carreño,

Helfer

et al. 2024

CPT Pharmacom & Syst Pharma

Self Cite

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“…In recent years, a handful of LC-MS/MS-based methods have been published to quantify neurotransmitters. These refer almost exclusively to mouse [ 15 , 16 ] and rat [ 39 , 40 ] brain tissue and mostly do not provide sufficient LOQs for neurotransmitter quantification in model organisms like C. elegans . Only Tufi et al present an LC-MS/MS analysis in zebrafish Danio rerio [ 41 ], while Barata et al published a method for neurotransmitter and related metabolites quantification in Daphnia magna [ 42 ].…”

Section: Introductionmentioning

confidence: 99%

A Reliable Method Based on Liquid Chromatography–Tandem Mass Spectrometry for the Simultaneous Quantification of Neurotransmitters in Caenorhabditis elegans

Weishaupt,

Kubens,

Ruecker

et al. 2023

Molecules

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Neurotransmitters like dopamine (DA), serotonin (SRT), γ-aminobutyric acid (GABA) and acetylcholine (ACh) are messenger molecules that play a pivotal role in transmitting excitation between neurons across chemical synapses, thus enabling complex processes in the central nervous system (CNS). Balance in neurotransmitter homeostasis is essential, and altered neurotransmitter levels are associated with various neurological disorders, e.g., loss of dopaminergic neurons (Parkinson’s disease) or altered ACh synthesis (Alzheimer’s disease). Therefore, it is crucial to possess adequate tools to assess precise neurotransmitter levels, and to apply targeted therapies. An established in vivo model to study neurotoxicity is the model organism Caenorhabditis elegans (C. elegans), as its neurons have been well characterized and functionally are analogous to mammals. We have developed a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method including a sample preparation assuring neurotransmitter stability, which allows a simultaneous neurotransmitter quantification of DA, SRT, GABA and ACh in C. elegans, but can easily be applied to other matrices. LC-MS/MS combined with isotope-labeled standards is the tool of choice, due to its otherwise unattainable sensitivity and specificity. Using C. elegans together with our analytically validated and verified method provides a powerful tool to evaluate mechanisms of neurotoxicity, and furthermore to identify possible therapeutic approaches.

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Magnetic borate-modified Mxene: A highly affinity material for the extraction of catecholamines

Pang

Shi

et al. 2021

Analytica Chimica Acta

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Quantification of neurotransmitters in microdialysate samples following quetiapine dosing to schizophrenia phenotyped rats using a validated LC-MS/MS method

Cited by 6 publications

References 30 publications

Pharmacokinetic/pharmacodynamic modeling of cortical dopamine concentrations after quetiapine lipid core nanocapsules administration to schizophrenia phenotyped rats

Pharmacokinetic/pharmacodynamic modeling of cortical dopamine concentrations after quetiapine lipid core nanocapsules administration to schizophrenia phenotyped rats

A Reliable Method Based on Liquid Chromatography–Tandem Mass Spectrometry for the Simultaneous Quantification of Neurotransmitters in Caenorhabditis elegans

Magnetic borate-modified Mxene: A highly affinity material for the extraction of catecholamines

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