Partial-onset Seizures In Adults Research Articles

Zirconia nanoparticles/carbon quantum dots modified carbon paste electrode as electrochemical sensor for determination of antiepileptic drug eslicarbazepine acetate in bulk and pharmaceutical dosage form

A new, sensitive and selective electrochemical method has been developed for determination of the antiepileptic prodrug eslicarbazepine acetate (ESL) that is used for the treatment of partial-onset seizures in adults with epilepsy. It belongs to the class of sodium channel blockers called dibenzoazepine family. A novel modified zirconia nanoparticles carbon paste nanocomposite, carbon dots sensor prepared from banana peels by solvothermal method has been fabricated. The voltammetric method is based on the direct anodic oxidation of ESL at the electrode surface using differential pulse voltammetry. Under the optimum experimental conditions, ESL exhibited a linear relationship in the range of 3.04 × 10-8 to 9.66 × 10-5 M with a lower detection limit of 7.57 × 10-9 M and quantification limit of 2.29 × 10-8 M. The proposed method was validated according to ICH guidelines and was applied for estimating ESL in raw material showing high accuracy and precision with successful application on tablet dosage form.

Cenobamate (Xcopri)


 CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
 The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.
 This review assesses cenobamate (Xcopri), 12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg, 200 mg tablet, oral.
 Indication: As adjunctive therapy in the management of partial onset seizures in adults with epilepsy who are not satisfactorily controlled with conventional therapy.

Cenobamate (Xcopri)


 CADTH recommends that Xcopri should be reimbursed by public drug plans as adjunctive therapy in the management of partial onset seizures in adults with epilepsy whose seizures are not satisfactorily controlled with conventional therapy, if certain conditions are met.
 Xcopri should only be reimbursed for the management of partial onset seizures in adults with epilepsy whose seizures are not satisfactorily controlled with conventional therapy, according to the criteria used by the public drug plans for other third generation antiseizure medication (ASMs) that are currently reimbursed for the management of partial onset seizures in adults with epilepsy whose seizures are not satisfactorily controlled with conventional therapy.
 Xcopri should only be reimbursed if the daily cost of Xcopri is the same as or lower than the daily cost of other third generation adjunctive therapies (lacosamide, brivaracetam, eslicarbazepine, and perampanel), and if the potential budget impact of funding Xcopri is addressed.

A retrospective non-interventional study evaluating the pharmacokinetic interactions between cenobamate and clobazam.

Cenobamate is an antiseizure medication (ASM) approved for the treatment of partial-onset seizures in adults. As both an inductor and an inhibitor of hepatic enzymes, cenobamate affects the metabolism of other ASMs, among which is clobazam. To our knowledge, the extent of interaction between cenobamate and clobazam and its clinical significance have not been studied yet. In this retrospective study we assessed serum concentrations of clobazam and N-desmethylclobazam (NCLB)in five patients before and after co-medication with cenobamate and calculated the percentage increase in concentration-to-dose ratio (CDR) of both. We were able to demonstrate that the addition of cenobamate resulted in an increase in serum concentration and consequently in CDR of NCLB in all patients. However this occurred in variable degrees: NCLB concentration showed an increase of 1208 μg/L (CDR145%) in one patient and between 1691 μ/L (CDR 819%) and 3995 μ/L (CDR 1852%) in the other four. This resulted in fatigue, which improved after dose reduction of CLB. Therefore, it is to be concluded that concomitant administration of cenobamate and clobazam can lead to a substantial increase in serum concentrations of NCLB. This can have a positive therapeutic effect on one hand; however, on the other hand, this can lead to unwanted fatigue.

Brivaracetam to Treat Partial Onset Seizures in Adults.

Seizures are a hyperexcitable, and hypersynchronous imbalance between excitatory and inhibitory factors (E/I imbalance) in neurotransmission, and epilepsy is the recurrent manifestation of seizures within a reasonable time frame and without being attributable to a reversible cause. Brivaracetam is a derivative of the antiepileptic agent, levetiracetam, that is used as adjuvant therapy for focal onset seizures. It was approved by the FDA in 2016 and has shown promising results with minimal adverse effect reactions in clinical trials. Brivaracetam has been used in multiple clinical trials at various dosages in adults that have partial-onset seizures refractory to conventional treatment. A meta-analysis in 2016 showed that brivaracetam as adjunctive therapy was statically significant in its reduction of adults with drug-refractory seizure frequency.1 The most commonly reported adverse effects that patients who were taking brivaracetam experienced were somnolence, headache, and dizziness. Further studies are necessary to conclude long term efficacy and safety profile of brivaracetam. The treatment of epilepsy with pharmacologic agents is a difficult task due to balancing the efficacy of the drug with the side effect profile that will allow for the best quality of life for the patient. There are approximately 30 antiepileptic agents for clinicians to choose from. Brivaracetam is a novel antiepileptic agent that was approved for use by the FDA in 2016 and is showing promising results as monotherapy and adjunctive therapy in individuals with drug-refractory focal seizures while minimizing adverse drug reactions.

Neuropharmacology of Levetiracetam as Anti-epileptic Medication

United state food and drug administration approved Levetiracetam on 30th November 1999 for the use as adjuanctive therapy in the treatment of partial onset seizures in adults with epilepsy. Therapeutic indications of Levetiracetam includes monotherapy in the treatment of partial onset seizures with or without secondary generalisation in adults and adolescents from 16 years of age with newly diagnosed epilepsy. Levetiracetam is indicated as adjunctive therapy in the treatment of partial onset seizures with or without secondary generalisation in adults, adolescents, children and infants from 1 month of age with epilepsy, in the treatment of myoclonic seizures in adults and adolescents from 12 years of age with juvenile myoclonic epilepsy, in the treatment of primary generalised tonic-clonic seizures in adults and adolescents from 12 years of age with idiopathic generalised epilepsy. This article describes the pharmacological aspects of Levetiracetam that will helful to health professionals.

Use of lacosamide in children: experience of a tertiary medical care center in Brazil.

Lacosamide (LCM) is a third-generation anti-seizure drug approved in Europe and the United States, either as a monotherapy or adjunctive therapy, to treat partial-onset seizures in adults, adolescents, and children. In Brazil, LCM is licensed for treatment only in patients older than 16 years of age. To evaluate a cohort of children presenting with refractory epilepsy who received LCM as an add-on therapy and observe the response and tolerability to the LCM treatment. A retrospective cohort study conducted in a tertiary health care facility, which included 26 children, aged up to 16 years, who presented with refractory epilepsy and received LCM as an add-on treatment. The follow-up visits were scheduled every 3 months until 9 months of treatment with LCM. After 3 months of LCM administration, in 73.1% of the children, there was a reduction of > 50% in the frequency of seizures, and this clinical improvement was maintained in most patients (73.9%) for the following 9 months. Mild (such as, somnolence and behavioral changes) or severe (seizure worsening) adverse effects were observed in two and three children respectively. Among responders to LCM, there was a higher prevalence of males, fewer concomitant anti-seizure drugs, and lower percentage of patients using sodium channel blockers. Lacosamide should be considered as an early treatment option in pediatric patients with refractory epilepsy, mainly focal seizures.

Method Development and Validation of a Novel UHPLC Coupled with MS/MS System for the Estimation of Brivaracetam in Human (K2EDTA) Plasma Samples and its Application to Pharmacokinetic Study

Background: Brivaracetam is a novel antiepileptic drug clinically approved for the treatment of partial onset seizures in adults and adolescents. It has some abuse potential and assigns to Schedule V category under the Controlled Substance Act by the Drug Enforcement Administration. It is essential to develop a faster, simple, and highly sensitive method for the quantification of Brivaracetam in human plasma by employing simple liquid-liquid extraction. Objective: The objective of this study is to develop and validate a novel UHPLC-MS/MS method for the estimation of brivaracetam in human plasma samples and application to pharmacokinetic study. Methods: An ultra-high-pressure liquid chromatography-tandem mass spectrometry method was developed and validated according to current regulatory guidelines for bioanalytical methods. Sample processing (50 μL) involved only a simple liquid-liquid extraction by ethyl acetate as extraction solvent. Brivaracetam-d7 was used as an internal standard. The chromatographic analysis was performed by a Unisol C18 (4.6 X 100 mm, 5μm) column using 0.1% formic acid in water/acetonitrile (20/80 V/V) as an isocratic mobile phase, at a flow rate of 1.0 mL/min with a run time of 2.2 min. Brivaracetam and its internal standard Brivaracetam D7 were detected and quantified in positive ion mode using multiple reaction monitoring transitions at m/z 213.100→168.100 and m/z 220.000→175.100, respectively. The developed method was applied to assess pharmacokinetic parameters like Cmax, Tmax, t1/2 and AUC for Brivaracetam in healthy, male, and adult humans. Results: The method was validated over a concentration range of 20.000 ng/mL to 4000. 000 ng/mL. Both intra- and inter-assay precision and accuracy were <15% for all quality control samples. No matrix effect was observed. Pharmacokinetic results showed that test formulation is bioequivalent with reference formulation. Conclusion: The present assay is faster, highly sensitive and simpler than previously published analytical reports for brivaracetam in human plasma samples and is suitable for pharmacokinetic evaluation of any marketed formulation.

Cenobamate for treatment-resistant focal seizures: current evidence and place in therapy.

BackgroundCenobamate is newly approved for partial-onset seizures in adults, albeit the mechanism of its action remain poorly understood.Methods This article aims to review the efficacy, safety, and tolerability of cenobamate in treating partial-onset seizures.Data Collection:The English language articles were searched in the National Institute of Health clinical trials registry, PubMed, and the Cochrane library between 2010 and June 2021 using the keywords cenobamate, YKP 3089, and seizure, and filter “trial” was applied. Results:A total of 31 articles were retrieved. Eventually, two randomized, double-blind, multicenter clinical trials involving 659 patients were analyzed. Cenobamate has shown significant reduction in seizure frequency compared to placebo. In cenobamate group, a greater number of participants showed ≥50% reduction in seizure frequency, adverse effects, and drug discontinuation compared to placebo. Multiple drug-drug interactions with other anti-seizure drugs were also observed.ConclusionsBased on the findings of these trials, cenobamate seems to be an attractive option for treatment-resistant partial-onset seizures; however, multiple treatment-related adverse effects and drug-drug interactions are the areas of concern.

Cenobamate, a Sodium Channel Inhibitor and Positive Allosteric Modulator of GABAA Ion Channels, for Partial Onset Seizures in Adults: A Comprehensive Review and Clinical Implications.

Medical management of epilepsy seeks to eliminate or to reduce the frequency of seizures, help patients maintain a normal lifestyle, and maintain psychosocial and occupational activities, while avoiding the negative side effects of long-term treatment. Current FDA approved drugs have been shown to have similar efficacy; however, they all share a commonality of having side effects that have the potential to significantly reduce a patient’s quality of life. Cenobamate, a newly-FDA approved drug used to treat partial-onset seizures in adult patients, has demonstrated promise in that it works on two proposed mechanisms that are commonly associated with epilepsy. Cenobamate acts as a positive allosteric modulator of the GABAA ion channels and is effective in reducing repetitive neuronal firing by inhibition of voltage-gated sodium channels, although the complete mechanism of action is currently unknown. The efficacy of Cenobamate with its low toxicity and adverse drug reaction profile emphasizes the need to further evaluate antiepileptic therapies containing sulfamoylphenyl and/or carbamate moieties in their chemical structure. Recent studies have found more patients to be seizure free during the maintenance period when compared to placebo. The most common side effects reported in with Cenobamate are somnolence, dizziness, headache, nausea, and fatigue. There are currently ongoing phase III studies looking to further evaluate the long-term benefits of Cenobamate and investigate adverse events.

New Treatment for Partial-Onset Seizures in Adults.

Cenobamate (Xcopri) is now approved to treat partial-onset seizures in adults.Serious adverse effects include drug reaction with eosinophilia and systemic symptoms (also called multiorgan hypersensitivity) and a shortened QT interval.

Effectiveness of eslicarbazepine acetate in dependency of baseline anticonvulsant therapy: Results from a German prospective multicenter clinical practice study

Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug (AED) approved as monotherapy for partial-onset seizures in adults and as adjunctive therapy in patients aged above 6 years in the European Union (EU). The prospective observational Zebinix Effects in DEpendency of BAseline Conditions (ZEDEBAC) study aimed at investigating the effectiveness of ESL in clinical practice, with ESL being administered as monotherapy (mono group), as only add-on to a current monotherapy (1+ group), or as add-on to ≥2 baseline AEDs (≥2+ group). In total, 237 patients were included, 35 in the mono group, 114 in the 1+, and 88 in the ≥2+ group. Six-month retention rates were 93.9%, 78.0%, and 75.3% in the mono, 1+, and ≥2+ group. There were 90.5%, 77.6%, and 48.3% of patients in the mono, 1+, and ≥2+ groups who were responders (patients with a ≥50% reduction in seizure frequency at follow-up vs. baseline). Seizure freedom rates were 81.5%, 47.9%, and 23.4%, respectively. Adverse drug reactions (ADRs) occurred in 11.4% of patients of the mono, 19.3% of the 1+, and 28.4% of patients of the ≥2+ group. Hyponatremia was reported as ADR in 3.4% of all patients. Although baseline variables differed considerably, with most elderly patients with tumor-related and vascular etiologies in the mono group and most patients with refractory epilepsies with pronounced use of concomitant sodium channel blockers (SCBs) in the ≥2+ group, retention as a measure of real-life effectiveness turned out not to be substantially different and favorable in all groups.

An Investigation into Retigabine (Ezogabine) Associated Dyspigmentation in Rat Eyes by MALDI Imaging Mass Spectrometry.

Retigabine (RTG) is an antiepileptic drug approved as an adjunctive treatment for refractory partial-onset seizures in adults. In April 2013, the Food and Drug Administration issued a warning that RTG could cause changes in retinal pigmentation and discoloration of skin, resulting in a blue appearance. As part of a larger preclinical effort to gain a mechanistic understanding as to the origins of retinal pigment changes associated with RTG, we conducted a long-term repeat dosing study in rats. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) was used to determine the distribution of RTG and its metabolites in the rat eye following 13 and 39 weeks of dosing. IMS revealed the presence of RTG, a previously characterized N-acetyl metabolite of RTG (NAMR), and several species structurally related through the dimerization of RTG and NAMR. These species were highly localized to the melanin-containing layers of the uveal tract of the rat eye including the choroid, ciliary body, and iris, suggesting that the formation of these dimers occurs from melanin bound RTG and NAMR. Furthermore, several of the RTG-related dimers have UV absorbance which give them a purple color in solution. We propose that the melanin binding of RTG and NAMR effectively concentrates the two compounds to enable mixed condensation reactions to occur when the binding provides the proper geometry in the redox environment of the uveal tissues. High lateral resolution images illustrate that the blood-retinal barrier effectively restricts retinal access to RTG-related compounds. The spatial information provided by MALDI IMS was critical in contextualizing the homogenate concentrations of key RTG-related compounds and helped provide a basis for the mechanism of dimer formation.

Brivaracetam does not modulate ionotropic channels activated by glutamate, γ-aminobutyric acid, and glycine in hippocampal neurons.

Brivaracetam (BRV) is a selective, high-affinity ligand for synaptic vesicle protein 2A (SV2A), recently approved as adjunctive treatment for drug-refractory partial-onset seizures in adults. BRV binds SV2A with higher affinity than levetiracetam (LEV), and was shown to have a differential interaction with SV2A. Because LEV was reported to interact with multiple excitatory and inhibitory ligand-gated ion channels and that may impact its pharmacological profile, we were interested in determining whether BRV directly modulates inhibitory and excitatory ionotropic receptors in central neurons. Voltage-clamp experiments were performed in primary cultures of mouse hippocampal neurons. At a supratherapeutic concentration of 100μm, BRV was devoid of any direct effect on currents gated by γ-aminobutyric acidergic type A, glycine, kainate, N-methyl-d-aspartate, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid. Similarly to LEV, BRV reveals a potent ability to oppose the action of negative modulators on the inhibitory receptors. In conclusion, these results show that BRV contrasts with LEV by not displaying any direct action on inhibitory or excitatory postsynaptic ligand-gated receptors at therapeutic concentrations and thereby support BRV's role as a selective SV2A ligand. These findings add further evidence to the validity of SV2A as a relevant antiepileptic drug target and emphasize the potential for exploring further presynaptic mechanisms as a novel approach to antiepileptic drug discovery.

UPLC-MS/MS assay for identification and quantification of brivaracetam in plasma sample: Application to pharmacokinetic study in rats.

Brivaracetam (BVR) is a novel antiepileptic drug (AED), approved clinically for the treatment of partial onset seizures in adults and adolescents. It has some abuse potential and assigned to Schedule V category under the Controlled Substance Act by the Drug Enforcement Administration. Being an AED and drug of abuse, a sensitive and robust assay is necessary for determination of BVR in biological fluids. Herein, we report a sensitive and validated UPLC-MS/MS assay for identification and quantification of BVR in plasma samples. The samples were prepared by one step liquid liquid extraction method using tert-Butyl methyl ether as extracting solvent. BVR and internal standard (carbamazepine) were separated on Aquity BEH™ C-18 column and eluted by using gradient mobile phase combination of acetonitrile and 0.1% formic acid in water. The precursor to product ion transition of m/z 213.12→54.95 (qualifier), 213.12→168.10 (quantifier) for BVR, and m/z 237.06→193.25 for IS were used for MRM detection and quantification. The assay was validated according to USFDA and SWGTOX guidelines for method validation and all parameter results were within the acceptable limits. The calibration curves were found to be linear in concentration range of 1.98-2000ng/mL (r2≥0.995) having LOD and LLOQ of 0.80 and 1.98ng/mL, respectively. The assay was successfully employed in BVR pharmacokinetic study in rats and can be suitable for therapeutic drug monitoring, pharmacokinetic study and forensic analysis.

Prediction of efficacy for conversion from adjunctive therapy to monotherapy with eslicarbazepine acetate 800 mg once daily for partial-onset epilepsy.

PurposeEslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) indicated for partial-onset seizures (POS). Clinical studies of gradual conversion to ESL 1,200 and 1,600 mg QD monotherapies were previously conducted in patients with POS who were not well-controlled by 1 or 2 AEDs. This report describes modeling and simulation of plasma eslicarbazepine (primary active metabolite of ESL) concentrations and time to monotherapy study exit to predict efficacy for conversion to ESL monotherapy at a lower dose of 800 mg, as an option for patients requiring or not tolerating higher doses since this regimen is effective in adjunctive therapy for POS.Patients and methodsA previously developed population pharmacokinetic model for ESL monotherapy was used to predict minimum plasma eslicarbazepine concentration (Cmin) in 1,500 virtual patients taking 1 (n=1,000) or 2 (n=500) AEDs at baseline, treated with ESL 400 mg QD for 1 week, followed by 800 mg QD for 17 weeks (similar to ESL monotherapy trials where the other AEDs were withdrawn during the first 6 weeks following titration to the randomized ESL dose). Model-predicted Cmin as a time-varying covariate and number of baseline AEDs were used to determine the weekly probability of each patient meeting exit criteria (65.3% threshold) indicative of worsening seizure control in 500 simulated ESL monotherapy trials. A previously developed extended Cox proportional hazards exposure–response model was used to relate time-varying eslicarbazepine exposure to the time to study exit.ResultsFor virtual patients receiving ESL monotherapy (800 mg QD), the 95% upper prediction limit for exit rate at 112 days of 34.9% in patients taking 1 AED at baseline was well below the 65.3% threshold from historical control trials, while the estimate for patients taking 2 AEDs (70.6%) was slightly above the historical control threshold.ConclusionThis model-based assessment supports conversion to ESL 800 mg QD monotherapy for POS in adults taking 1 AED. For patients taking 2 concomitant AEDs, however, prescribers should consider maintenance doses of 1,200 or 1,600 mg ESL QD to reduce the likelihood of seizure worsening if conversion to ESL monotherapy is contemplated.

Vagus nerve stimulation therapy in partial epilepsy: a review.

Epilepsy is a chronic neurological disorder characterized by recurrent, unprovoked epileptic seizures. The majority of people given a diagnosis of epilepsy have a good prognosis, but 20-30% will develop drug-resistant epilepsy. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with medically refractory epilepsy. It consists of chronic intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator (Neuro-Cybernetic Prosthesis). In 1997, the Food and Drug Administration approved VNS as adjunctive treatment for medically refractory partial-onset seizures in adults and adolescents. This article reviews the literature from 1988 to nowadays. We discuss thoroughly the anatomy and physiology of vagus nerve and the potential mechanisms of actions and clinical applications involved in VNS therapy, as well as the management, safety, tolerability and effectiveness of VNS therapy. VNS for partial seizures appears to be an effective and well tolerated treatment in adult and pediatric patients. People noted improvements in feelings of well-being, alertness, memory and thinking skills, as well as mood. The adverse effect profile is substantially different from the adverse effect profile associated with antiepileptic drugs, making VNS a potential alternative for patients with difficulty tolerating antiepileptic drug adverse effects. Despite the passing years and the advent of promising neuromodulation technologies, VNS remains an efficacy treatment for people with medically refractory epilepsy. Past and ongoing investigations in other indications have provided signals of the therapeutic potential in a wide variety of conditions.

Brivaracetam: First Global Approval.

Brivaracetam (Briviact(®)), a 4-n-propyl analogue of levetiracetam developed by UCB Pharma, has been approved in the EU as an adjunctive therapy for the treatment of partial-onset seizures. Brivaracetam binds to synaptic vesicle glycoprotein 2a (SV2A) in the brain with greater selectivity and 15- to 30-fold higher affinity than levetiracetam, as demonstrated in preclinical models, and has demonstrated efficacy in reducing the frequency of partial onset seizures in clinical trials. This article summarizes the milestones in the development of brivaracetam leading to this first approval for use as adjunctive therapy for uncontrolled partial-onset seizures in adults with epilepsy.

Acute or chronic use of lacosamide does not alter its distribution between serum and cerebrospinal fluid.

The site of action for antiepileptic drugs (AEDs) is within the brain; however, cerebrospinal fluid (CSF) concentration is highly variable. Lacosamide (LCM) is approved by the U.S. Food and Drug Administration (FDA) for treatment of partial-onset seizures in adults, and has linear pharmacokinetics in serum. Penetration across the blood-brain barrier (BBB) is unknown. This study aims to provide additional insights into the pharmacokinetics of LCM. Thirty adults undergoing craniotomy for treatment of intractable epilepsy or brain tumor were recruited and were either taking LCM long term (group 1, n = 15), or were LCM naive, receiving LCM as prophylaxis for surgery (group 2, n = 15). All patients received one intravenous (IV) dose (15 min infusion) immediately prior to craniotomy. CSF and arterial blood were collected simultaneously following craniotomy. LCM concentrations were measured in serum and CSF. LCM concentration differences between groups 1 and 2 for both CSF and serum were statistically significant (p ≤ 0.0005), but there was no statistically significant difference in CSF/serum ratios (group 1 = 0.726 ± 0.231; group 2 = 0.556 ±0.241; p = 0.0585). LCM concentration in serum correlated positively with CSF concentration in group 1 (Pearson r = 0.8527, p < 0.0001). The time interval between the end of dose delivery and sample collection correlated positively with the CSF/serum ratio for the drug-naive group (Pearson r = 0.6525; p = 0.0084). Treatment with other AEDs did not affect LCM distribution between serum and CSF. Although chronic dosing resulted in higher LCM concentrations in serum and CSF compared to drug-naive patients, the CSF/serum ratio was not affected by LCM pretreatment. These data suggest that LCM serum concentration may reliably predict CSF concentration.

High-throughput method for the quantification of lacosamide in serum using ultrafast SPE-MS/MS.

Lacosamide is an anticonvulsant drug approved for adjunctive therapy of partial-onset seizures in adults. Monitoring serum lacosamide concentrations may be useful in assessing compliance and optimizing therapy. The clinical need for faster turn-around-times and increased testing volumes has led to the desire to develop faster methods of analysis for higher throughput of samples. Fifty microliters of calibration standards, quality controls, and patient samples were precipitated with methanol containing deuterated internal standard. The supernatant was then diluted with aqueous mobile phase and injected on an ultrafast solid-phase extraction-mass spectrometry with a cycle time of <10 seconds per sample. The analytic linear range for the assay was 0.5-50.0 mcg/mL with a limit of detection of 0.05 mcg/mL. The assay showed interassay and intraassay precision coefficient of variations <7%, with no significant carryover after a sample twice the upper limit of quantitation, and no interference from the top 24 prescribed drugs, other anticonvulsants, or common drugs of abuse. Analytical accuracy was determined by comparing 26 results (19 patients, 7 standards and quality control) with a reference laboratory using liquid chromatography-mass spectrometry in addition to 11 proficiency samples from the LGC Standards Proficiency Testing survey. The results were compared using a standard linear regression with the equation of the line being y = 1.093x - 0.166, with an r(2) = 0.99, and a y intercept 95% confidence interval that included zero. Herein, the authors present a method for the quantification of lacosamide in serum with ultrafast solid-phase extraction-mass spectrometry that uses 50 μL of sample, is linear from 0.5 to 50 mcg/mL, has interassay and intraassay coefficient of variations of <7%, and has much faster sample cycle times with similar analytic results compared with traditional liquid chromatography-mass spectrometry.