Quantitative Analysis of Cenobamate and Concomitant Anti-Seizure Medications in Human Plasma via Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry.

Cenobamate (CNB) is a new anti-seizure medication (ASM) recently introduced in clinical practice after approval by the FDA and EMA for the add-on treatment of focal onset seizures in adult patients. Although its mechanism of action has not been fully understood, CNB showed promising clinical efficacy in patients treated with concomitant ASMs. The accessibility of CNB could pave a way for the treatment of refractory or drug-resistant epilepsies, which still affect at least one-third of the patients under pharmacological treatment.

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) 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.

Therapeutic Drug Monitoring of Antiseizure Medications Using Volumetric Absorptive Microsampling: Where Are We?

Therapeutic drug monitoring (TDM) of antiseizure medications (ASMs) represents a valuable tool to establish an appropriate patient therapy, to collect important information about drugs' interactions and to evaluate patient's metabolic capabilities. In recent years, a new volumetric absorptive microsampling technique using VAMS technology and Mitra devices, consisting of a sampling technique for the collection of fixed-volume capillary blood, was developed. These new devices provide a new home-sampling technique for whole blood that has been spread out to simplify sample collection from finger-pricks.

Synergistic Effect of Perampanel and Temozolomide in Human Glioma Cell Lines.

Glioblastoma is characterized by a high proliferative rate and drug resistance. The standard of care includes maximal safe surgery, followed by radiotherapy and temozolomide chemotherapy. The expression of glutamate receptors has been previously reported in human glioma cell lines.

A new LC-MS/MS confirmation method for the determination of 17 drugs of abuse in oral fluid and its application to real samples.

A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) confirmation method for the direct analysis of 17 drugs starting from 200μL of diluted oral fluid (OF), in a single chromatographic run, was developed and validated. Cocaine, benzoylecgonine (BEG), cocaethylene, Δ-9-tetrahydrocannabinol (Δ-9-THC), buprenorphine, 6-acetylmorphine (6AM), morphine, codeine, methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), methylenedioxyamphetamine (MDA), 3,4-Methylenedioxy-N-ethylamphetamine (MDE), ketamine, N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB) were determined in a chromatographic run of 12min only with no sample pre-treatment, after the addition of 15 different internal standards (ISs). The method met all requirements in terms of linearity, accuracy (precision and trueness), recovery, and stability requested by FDA guidelines.

Volumetric Absorptive Microsampling: A New Sampling Tool for Therapeutic Drug Monitoring of Antiepileptic Drugs.

Background: Volumetric absorptive microsampling (VAMS) is a novel sampling technique for the collection of fixed-volume capillary blood. In this study, a new analytical method was developed and used to quantify 14 different antiepileptic drugs (AEDs) and 2 active metabolites in samples collected by VAMS. These data were compared with concentration measurements in plasma.

LC-MS/MS-Based Quantification of 9 Antiepileptic Drugs From a Dried Sample Spot Device.

Background: Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) is commonly performed on plasma or serum. The use of dried plasma spots (DPSs) could represent a useful tool to facilitate sample shipment to reference laboratories. In this article, the authors describe the application of a commercially available UHPLC-MS/MS method for the determination of 9 commonly prescribed AEDs (levetiracetam, lacosamide, topiramate, ethosuximide, lamotrigine, rufinamide, zonisamide, primidone, and oxcarbazepine and its active metabolite 10-OH-monohydroxycarbazepine) to DPS collected on dried sample spot devices (DSSDs).

A Liquid Chromatography-Mass Spectrometry Assay for Determination of Perampanel and Concomitant Antiepileptic Drugs in the Plasma of Patients With Epilepsy Compared With a Fluorescent HPLC Assay.

Background: Perampanel is a novel noncompetitive selective antagonist at the postsynaptic ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) glutamate receptor, which is approved as an adjunctive agent for the treatment of partial-onset seizure with or without secondary generalization and for primary generalized tonic-clonic seizure in patients with epilepsy who are at least 12 years of age. Limited information is available about the clinical utility of therapeutic drug monitoring of perampanel and therapeutic ranges are so far not established. Therefore, perampanel titration should be performed especially in case of insufficient success of the drug.

Evaluation of a Novel Immunoassay for Lacosamide Therapeutic Drug Monitoring: Comparison With a Liquid Chromatography-Mass Spectrometry Assay.

Background: Monitoring serum levels of lacosamide, other than to establish individualized reference ranges may be helpful in several settings, including patients with liver and/or kidney failure or settings that may result in altered pharmacokinetic characteristics and to assess patients' compliance with therapy. In this study, the EurekaOne liquid chromatography-mass spectrometry (LC-MS/MS) method (in use method) and the ARK immunoassay method (new method) for lacosamide monitoring were compared.

Methods: Lacosamide concentrations were determined in 39 patient samples using (1) antiepileptic drug LC-MS/MS kit by EurekaOne on a Thermo Fisher Scientific TSQuantum Access Max system and (2) the lacosamide immunoassay by ARK Diagnostic Inc.