Synthesis and characterization of miniaturized aptamer-based monolithic sorbent for selective extraction of β-amyloid peptides from cerebrospinal fluid.

The ratio between beta-amyloid (Aβ) peptides 40 and 42 is recognized as a biomarker for Alzheimer's disease, playing a significant role in early diagnosis and disease progression monitoring. Aβ peptides are present at trace levels in cerebrospinal fluid, therefore, developing a new selective extraction procedure is essential for isolating targeted biomarkers from the matrix interferents, ensuring accurate identification and quantification. In this study, a hybrid organic-silica monolith was synthesized in a 530 µm inner diameter-capillary and used for the covalent grafting of beta amyloid peptide aptamers.

A novel restricted access-anion exchange organic monolithic phase for determining homocysteine and homocysteic acid in cerebrospinal fluid samples obtained from Alzheimer's disease patients by in-tube SPME-LC-MS/MS.

Background: High circulating concentrations of homocysteine (Hcy), a sulfur-containing amino acid, and homocysteic acid (HCA), an Hcy oxidized derivative, are an independent risk factor for developing Alzheimer's disease (AD), a neurodegenerative disorder that causes progressive cognitive decline. Therefore, these two endogenous compounds might be potential AD biomarkers. Nevertheless, few studies have attempted to quantify Hcy and HCA in the cerebrospinal fluid (CSF), the best validated fluid for evaluating neurodegenerative disorders.

Cannabidiol improves L-DOPA-induced dyskinesia and modulates neuroinflammation and the endocannabinoid, endovanilloid and nitrergic systems.

Despite the widespread use of L-3,4-dihydroxyphenylalanine (L-DOPA) as the gold standard for dopamine (DA) replacement in Parkinson's Disease (PD), its prolonged administration frequently leads to L-DOPA-induced dyskinesia (LID), a significant therapeutic challenge. Modulating the endocannabinoid system has emerged as a promising approach for managing LID. This study explored whether cannabidiol (CBD), a non-psychoactive compound of Cannabis sativa, and PECS-101, a fluorinated derivative of CBD, could mitigate the onset and progression of LID.

A Disposable Pipette Extraction-UHPLC-MS/MS Method Based on Removal of Phospholipids to Determine Anandamide, 2-Arachidonoylglycerol, Cannabidiol, and Δ-Tetrahydrocannabidiol in Plasma Samples.

Cannabidiol (CBD) and Δ-tetrahydrocannabinol (THC), the main components of Cannabis sativa plants, can interact with specific cell receptors known as cannabinoid receptors (CBs). The endogenous compounds anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are CB agonists, and, alongside enzymes, they constitute the endocannabinoid system (ECS) and take part in neuromodulation. Several LC-MS/MS methods have been developed to quantify these compounds in biological matrixes, but a fast and simple method that can determine these analytes in plasma samples simultaneously is not available.

Universal carbon nanotubes-polybenzimidazole SPME coating and its application for both gas and liquid chromatography.

In this study, we present a novel combination of carbon nanotubes (CNT), widely used as a sorbent material in solid-phase extraction-based methodologies, with polybenzimidazole (PBI), recently introduced as a universal binder for physical immobilization of sorbent particles. This combination was used to prepare CNT-PBI coated solid-phase microextraction (SPME) devices (fibers, arrows, and blades) suitable for both thermal and solvent desorption. The resulting CNT-PBI SPME devices presented excellent mechanical resistance and high thermal stability, capable of enduring multiple thermal desorption cycles without compromising extraction efficiency.

Advances in sample preparation and HPLC-MS/MS methods for determining amyloid-β peptide in biological samples: a review.

Alzheimer's disease (AD), a neurological disorder, is a major public health concern and the most common form of dementia. Its typical symptoms include memory loss, confusion, changes in personality, and cognitive impairment, which result in patients gradually losing independence. Over the last decades, some studies have focused on searching for effective biomarkers as early diagnostic indicators of AD.

Magnetic restricted-access carbon nanotubes for SPME to determine cannabinoids in plasma samples by UHPLC-MS/MS.

This manuscript describes the development of magnetic restricted-access carbon nanotubes (M-RACNTs) for use as SPME sorbent to determine cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in human plasma samples by UHPLC-MS/MS. The adsorptive phase was immobilized on an SPME device by electromagnetic interactions between the M-RACNTs and a cylindrical neodymium magnet (3-mm diameter x 8-mm height) attached to a stainless-steel rod (3-mm diameter x 40-mm height). The M-RACNTs were synthesized by incorporating FeO magnetic nanoparticles (MNPs) into commercial carbon nanotubes (CNTs); then the surface of the resulting sorbent was further coated with a layer of bovine serum albumin (BSA).

Current advances and applications of online sample preparation techniques for miniaturized liquid chromatography systems.

Miniaturized liquid chromatography (LC) has been recognized as one of the most important analytical methods in several research fields. Reduced analytical work-scale provides superior chromatographic resolution and decreases sample and organic solvent consumption. However, frequent clogging of tubing connections and use of small sample volumes are significant limitations when high throughput and sensitive analyses are required.

Circulating Endocannabinoids in Huntington's Disease: An Exploratory Cross-Sectional Study.

Huntington's disease (HD) is an inherited neurodegenerative disease characterized by motor, cognitive and behavioral deficits. Some evidence suggests that the endocannabinoid system participates in the pathophysiology of HD. We conducted a cross-sectional study comparing plasma levels of anandamide and 2-arachidonoylglycerol in manifest HD gene-expansion carriers (HDGEC) and healthy controls, finding no difference in endocannabinoid levels between the groups.

Novel materials as capillary coatings for in-tube solid-phase microextraction for bioanalysis.

In-tube solid-phase microextraction with a capillary column as extraction device can be directly coupled with high-performance liquid chromatography systems (HPLC). The in-tube solid-phase microextraction technique has been continuously developed since it was introduced in 1997. New couplings have also been evaluated on the basis of state-of-the-art HPLC instruments.

Pipette tip micro-solid phase extraction (octyl-functionalized hybrid silica monolith) and ultra-high-performance liquid chromatography-tandem mass spectrometry to determine cannabidiol and tetrahydrocannabinol in plasma samples.

This manuscript describes the development of an innovative method to determine cannabinoids (cannabidiol and tetrahydrocannabinol) in human plasma samples by pipette tip micro-solid phase extraction and liquid chromatography-mass spectrometry/mass spectromtery. An octyl-functionalized hybrid silica monolith, which had been synthesized and characterized, was used as a selective stationary phase. The octyl-functionalized hybrid silica monoliths presented high permeability and adequate mechanical strength.

In-tube solid-phase microextraction directly coupled to tandem mass spectrometry for anandamide and 2-arachidonoylglycerol determination in rat brain samples from an animal model of Parkinson's disease.

To evaluate the endocannabinoid system in an animal model of Parkinson's disease, in-tube solid-phase microextraction (in-tube SPME) was directly coupled to a tandem mass spectrometry (MS/MS) system for determination of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in rat brain samples. In-tube SPME-which consisted of a microtube of restricted access material (RAM) with a hydrophilic diol external surface and a hydrophobic octyl inner surface-efficiently excluded (up to 95%) macromolecules from the biological samples and selectively pre-concentrated the analytes. In-tube SPME parameters, such as sample volume, mobile phases, flow rate, and pre-concentration time, were evaluated to improve the extraction efficiency and throughput performance.

A micro salting-out assisted liquid-liquid extraction combined with ultra-high performance liquid chromatography tandem mass spectrometry to determine anandamide and 2-arachidonoylglycerol in rat brain samples.

A simple and reliable method was developed and validated to determine the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in rat brain samples by micro salting-out assisted liquid-liquid extraction combined with ultra-high performance liquid chromatography tandem mass spectrometry (SALLLE/UHPLC-MS/MS). The SALLE parameters (brain homogenate volume, salting-out agent, salt concentration, salt solution volume, organic solvent, organic solvent volume, and centrifugation temperature) were optimized to improve sensitivity and selectivity of the method. The SALLE/UHPLC-MS/MS method presented linear ranges from 2.

Endocannabinoid levels in patients with Parkinson's disease with and without levodopa-induced dyskinesias.

Levodopa-induced dyskinesias (LID) in Parkinson's disease (PD) are frequent complications, and the endocannabinoid system has a role on its pathophysiology. To test the hypothesis that the functioning of the endocannabinoid system would be altered in PD and in LID by measuring plasma and CSF levels of α-N-arachidonoylethanolamine (AEA) and 2-arachidonoyl-glycerol (2-AG) in patients with PD with and without LID and in healthy controls. Blood and CSF samples were collected from 20 healthy controls, 23 patients with PD without LID, and 24 patients with PD with LID.

Restricted access carbon nanotube for microextraction by packed sorbent to determine antipsychotics in plasma samples by high-performance liquid chromatography-tandem mass spectrometry.

This manuscript describes the development of the restricted access carbon nanotube (RACNT) as a selective stationary phase for microextraction by packed sorbent (MEPS) to determine antipsychotics (chlorpromazine, clozapine, olanzapine, and quetiapine) in untreated plasma samples from schizophrenic patients by ultra-high liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The synthesis was achieved by chemically covering commercial multi-walled carbon nanotubes with bovine serum albumin (BSA) to subsequently pack the material in a polyethylene conical tube (1000 μL). The RACNTs' sorbents were able to exclude about 97% of the plasma proteins, maintaining the same performance for about 100 assays.

In-tube solid-phase microextraction with a dummy molecularly imprinted monolithic capillary coupled to ultra-performance liquid chromatography-tandem mass spectrometry to determine cannabinoids in plasma samples.

A selective and sensitive method that uses automated in-tube solid-phase microextraction coupled to ultra-performance liquid chromatography-tandem mass spectrometry (in-tube SPME/UHPLC-MS/MS) was developed to determine cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) in plasma samples. A new dummy molecularly imprinted monolithic capillary (MIP monolith) for in-tube SPME was prepared by in situ polymerization in a fused silica capillary; hydrogenated cannabidiol was employed as dummy template. Fourier Transform Infrared Spectroscopy (FTIR) confirmed that the synthesis reagents were incorporated into the polymer chain.

Analysis of endocannabinoids in plasma samples by biocompatible solid-phase microextraction devices coupled to mass spectrometry.

Anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) represent two of the most important endocannabinoids (ECs) investigated in neurobiology as therapeutic targets for several mental disorders. However, the determination of these ECs in biological matrices remains a challenging task because of the low concentrations, low stability and high protein-bound (LogP ∼ 6). This work describes innovative analytical methods based on biocompatible SPME (Bio-SPME), SPME-UHPLC-MS/MS and Bio-SPME-Nano-ESI-MS/MS, to determine AEA and 2-AG in human plasma samples.

Determination of anandamide in cerebrospinal fluid samples by disposable pipette extraction and ultra-high performance liquid chromatography tandem mass spectrometry.

This work describes the development and validation of an ultra-high performance liquid chromatography tandem mass spectrometry method that uses disposable pipette extraction (DPX-UHPLC-MS/MS) to determine the endocannabinoid anandamide (AEA) in cerebrospinal fluid samples (CSF). The DPX parameters sorption equilibrium time, sample volume, number of draw-eject cycles, washing solvent volume, and elution solvent volume were optimized by design of experiments (DOE) techniques. The simple DPX protocol proposed herein required a reduced amount of CSF sample and organic solvent.

Schizophrenia: recent advances in LC-MS/MS methods to determine antipsychotic drugs in biological samples.

Schizophrenia is one of the most debilitating and costly illnesses worldwide. First-generation antipsychotics such as chlorpromazine and haloperidol succeeded in controlling the positive symptoms of schizophrenia, but had significant extrapyramidal effects that led to the search for new agents and the release of second-generation (or atypical) antipsychotics. These drugs had a lower risk of adverse motor symptoms.

Recent advances in LC-MS/MS methods to determine endocannabinoids in biological samples: Application in neurodegenerative diseases.

Endocannabinoids (ECs) are endogenous lipid-based retrograde neurotransmitters that bind to cannabinoid receptors [cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2)]. Many ECs have been characterized; anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) are still considered the primary ECs signaling mediators. Dysregulation of ECs has been implicated in a wide range of pathologies, including neurodegenerative diseases.

Recent development of chromatographic methods to determine parabens in breast milk samples: A review.

Parabens have been widely used as antimicrobial preservatives in food, drugs, and cosmetics for over 60 years. These endocrine disruptors can alter both the wildlife and the human hormone function. Determining these compounds in human milk is important because breast milk plays an important role in infant growth and in neurocognitive development.

Pipette tip dummy molecularly imprinted solid-phase extraction of Bisphenol A from urine samples and analysis by gas chromatography coupled to mass spectrometry.

Molecularly imprinted polymers (MIPs) were synthesized and used as sorbent for Bisphenol A (BPA) pipette tip solid-phase microextraction from urine samples and BPA analysis by gas chromatography coupled to mass spectrometry (GC-MS). The MIPs were synthesized by the sol-gel methodology. Aminopropyltriethoxysilane (APTES) and tetraethyl orthosilicate (TEOS) were used as functional monomer and cross-linking reagent, respectively.

A column switching ultrahigh-performance liquid chromatography-tandem mass spectrometry method to determine anandamide and 2-arachidonoylglycerol in plasma samples.

This study reports a fast, sensitive, and selective column switching ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to determine the endocannabinoids (eCBs), anandamide (AEA), and 2-arachidonoylglycerol (2-AG) in plasma samples. This bidimensional system used a restricted access media column (RP-8 ADS, 25 mm × 4 mm × 25 μM) in the first dimension and a core-shell Kinetex C18 (100 mm × 2, 1.7 mm × 1 μM) column in the second dimension, followed by detection in a mass spectrometer triple quadrupole (multiple reactions monitoring mode) operating in the positive mode.