Highly sensitive HPLC-MS/MS assay for the quantitation of ondansetron in rat plasma and rat brain tissue homogenate following administration of a very low subcutaneous dose

The objective of this study was to develop and validate a highly sensitive HPLC-MS/MS assay capable of quantifying ondansetron in rat plasma and rat brain homogenate following a low subcutaneous administration of 1.0 µg/kg. Ondansetron was extracted by protein precipitation with methanol containing labeled ondansetron. The chromatography was performed on a Thermo Scientific Aquasil C18 analytical column (100 x 2.1 mm I.D., 5 μm) operating at 40 °C. The mobile phase consisted of acetonitrile and 10 mM ammonium formate pH 3 at a ratio of 30:70, respectively. The flow rate was fixed at 300 µL/min and ondansetron and the internal standard were both eluted at 2.3 min. A linear (1/x) relationship was used to perform the calibration over an analytical range from 20.0 – 10,000 pg/mL in plasma and from 2.00 – 1,000 pg/mL in rat brain homogenate. The inter-batch precision and accuracy ranged from 3.7 to 4.7% and from 0.7 to 10.9% in rat plasma, respectively. The inter-batch precision and accuracy observed in rat brain was 4.5 to 6.4% and -5.1 to 4.9% respectively. The method met all requirements and the assay was suitable for the determination of the pharmacokinetic profile following a subcutaneous dose of 1.0 µg/kg body weight (BW) in rats.
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research

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The expression of the transmembrane protein 25 gene (Tmem25) is strongly influenced by glutamate ionotropic receptor kainate type subunit 4, and its function remains unknown. Here, we showed that TMEM25 was primarily localized to late endosomes in neurons. Electrophysiological experiments suggested that the effects of TMEM25 on neuronal excitability were likely mediated by N-methyl-d-aspartate receptors. TMEM25 affected the expression of the N-methyl-d-aspartate receptor NR2B subunit and interacted with NR2B, and both were colocalized to late endosome compartments. TMEM25 induced acidification changes in lysosome compartme...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Children with epilepsy frequently experience breakthrough seizures at home, in school, or in the community that are prolonged or in clusters. Although all patients with epilepsy warrant a systematic, evidence-based, drug rescue plan for breakthroughs outside the hospital, do pediatric epileptologists prescribe in a consistent approach? In this volume of The Journal Wallace et al present results from 36 experts from the Pediatric Epilepsy Consortium queried about which medications they prescribe for breakthroughs in various situations for developmentally delayed or developmentally typical children of various ages.
Source: The Journal of Pediatrics - Category: Pediatrics Authors: Tags: The Editors' Perspectives Source Type: research
We describe a boy with an SLC6A1 mutation and a milder phenotype, characterized by a learning disorder without intellectual disability, nonspecific dysmorphisms, and an electroencephalogram picture closely resembling that of myoclonic-atonic epilepsy with brief absence seizures that have appeared during the follow-up, responsive to valproic acid.
Source: Journal of Pediatric Neurosciences - Category: Neuroscience Authors: Source Type: research
Manjinder Randhawa, Sumeet R Dhawan, Sugantha Kumar, Bhanudeep Singanamala, Anmol Bhatia, Lokesh Saini, Naveen SankhyanJournal of Pediatric Neurosciences 2019 14(2):103-104A three-months boy presented with recurrent seizures. On examination, he was fair, had dilated scalp veins, sparse hypopigmented hair, and was hypotonic. X-ray of the skull showed wormian bones. The child was diagnosed with Menkes disease. The manuscript aims to emphasize dilated scalp veins in diagnosis of Menkes disease.
Source: Journal of Pediatric Neurosciences - Category: Neuroscience Authors: Source Type: research
Publication date: Available online 19 August 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Alexandra Simon, András Darcsi, Ágnes Kéry, Eszter RiethmüllerABSTRACTGinger, the rhizome of Zingiber officinale Roscoe is of great importance in the traditional medicine for the treatment of various diseases. More than 400 constituents have been reported in the plant, the most important ones being the gingerol and shogaol derivatives. Positive effects of ginger extracts and isolated [6]-gingerol have been proved in animal models of anxiety, Alzheimer’s disease, Parkinson&rsqu...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research
Psychogenic nonepileptic seizures (PNES) are of the most elusive phenomena in epileptology. Patients with PNES present episodes resembling epileptic seizures in their semiology yet lacking the underlying epileptic brain activity. These episodes are assumed...
Source: SafetyLit - Category: International Medicine & Public Health Tags: Ergonomics, Human Factors, Anthropometrics, Physiology Source Type: news
Publication date: Available online 17 August 2019Source: Physiology &BehaviorAuthor(s): Elizabeth Sahagun, Lauren M. Ward, Kimberly P. KinzigAbstractKetogenic diets (KDs) are high-fat, low-carbohydrate diets that have been used therapeutically for decades, most notably for the treatment of epilepsy and diabetes. Recent data, however, suggest that KD may impart protective effects on mood disorders. The current experiments test the hypothesis that KDs can protect from stress-induced symptoms of mood disorders. To test this, we assessed behavioral and neuroendocrine effects of KD in male and female Long Evans rats. Animal...
Source: Physiology and Behavior - Category: Physiology Source Type: research
Epilepsy is a common neurological disorder in which patients suffer seizures. Being able to predict the onset of a seizure before it occurs is important since this may facilitate the prevention of accidents and injury that can occur during seizures and additionally may help with pre-seizure delivery of medication or other interventions [1]. Electrical activity in the brain can be monitored using electroencephalogram (EEG) signals [2], which can be recorded from the scalp of patients, referred to as scalp EEG [3], or by implanting electrodes inside brain tissues during surgery, referred to as intracranial EEG signals (iEEG) [4].
Source: Seizure: European Journal of Epilepsy - Category: Neurology Authors: Tags: < ![CDATA[Review]] > Source Type: research
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Source: Epilepsy and Behavior - Category: Neurology Source Type: research
Publication date: Available online 17 August 2019Source: Epilepsy &BehaviorAuthor(s): Anastasia Brodovskaya, Jaideep KapurAbstractMapping the circuits underlying the generation and propagation of seizures is critically important for understanding their pathophysiology. We review evidence to suggest that circuits engaged in secondarily generalized seizures are likely to be more complex than those currently proposed. Focal seizures have been proposed to engage canonical thalamocortical circuits that mediate primarily generalized absence seizures, leading to secondarily generalized tonic–clonic seizures. In addition...
Source: Epilepsy and Behavior - Category: Neurology Source Type: research
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