Simultaneous Quantitation of Lamotrigine, Levetiracetam, 10-Hydroxycarbazepine, Topiramate, and Zonisamide in Serum Using HPLC-MS/MS

Carlow, Dean; Shi, Heng; Schofield, Ryan

doi:10.1007/978-1-4939-3252-8_4

Cited by 16 publications

(12 citation statements)

References 7 publications

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“…() and Deeb et al () methods, respectively]. More recently, Carlow, Shi, and Schofield () reported a method with a rapid run‐time (4 min), a small amount of sample required (50 μL) but a higher limit of quantification (0.5–1 μg/mL). Finally, practicability in routine TDM and robustness of presented method was confirmed by incurred samples reanalysis and clinical application in a large number of patients.…”

Section: Resultsmentioning

confidence: 99%

Simultaneous determination of four antiepileptic drugs in human plasma samples using an ultra‐high‐performance liquid chromatography tandem mass spectrometry method and its application in therapeutic drug monitoring

Dupouey

Doudka

Belo

et al. 2016

Biomedical Chromatography

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Therapeutic drug monitoring of antiepileptic drugs is widely practiced to achieve optimal efficacy and avoid adverse side effects. We describe an ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC/MS/MS) method developed for the monitoring of four frequently prescribed antiepileptic drugs - lamotrigine, levetiracetam, oxcarbazepine and topiramate. The main pharmacologically active metabolite of oxcarbazepine (mono-hydroxy-derivative metabolite, MHD) was also quantified. After addition of internal standards and a simple stage of protein precipitation, plasmatic samples were analyzed on a C column. All antiepileptic drugs were separated and quantified in 6 min, without interference. A good linearity was observed all over the calibration range (r > 0.99), up to 20 μg/mL (40 μg/mL for MHD). The limit of quantification was 0.20 μg/mL (0.40 μg/mL for MHD) with precision and accuracy ranging from 1.0 to 2.1% and from 96.7 to 110.8%, respectively. Intra- and inter-day precision and accuracy values were within 15%. No significant matrix effect was observed for all analytes. Clinical application was successfully evaluated in 259 samples from patients treated for epilepsy or bipolar disorders. In conclusion, a rapid, specific and sensitive UHPLC/MS/MS method was developed and validated for simultaneous quantification of antiepileptic drugs, suitable for therapeutic drug monitoring in neurology and psychiatry.

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Section: Resultsmentioning

confidence: 99%

Simultaneous determination of four antiepileptic drugs in human plasma samples using an ultra‐high‐performance liquid chromatography tandem mass spectrometry method and its application in therapeutic drug monitoring

Dupouey

Doudka

Belo

et al. 2016

Biomedical Chromatography

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“…The validated LC-MS/MS methods for the analysis of LTG in plasma, serum and DPS in the presence of other antiepileptics were also available [30,37,77,78,164]. The assays were characterized by high sensitivity with LOQ for LTG ranged from 0.005 [30] to 0.1 mg/L [78] in plasma and 0.25 mg/L in DPS [37].…”

Section: Lamotriginementioning

confidence: 99%

New Methods Used in Pharmacokinetics and Therapeutic Monitoring of the First and Newer Generations of Antiepileptic Drugs (AEDs)

et al. 2020

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The review presents data from the last few years on bioanalytical methods used in therapeutic drug monitoring (TDM) of the 1st–3rd generation and the newest antiepileptic drug (AEDs) cenobamate in patients with various forms of seizures. Chemical classification, structure, mechanism of action, pharmacokinetic data and therapeutic ranges for total and free fractions and interactions were collected. The primary data on bioanalytical methods for AEDs determination included biological matrices, sample preparation, dried blood spot (DBS) analysis, column resolution, detection method, validation parameters, and clinical utility. In conclusion, the most frequently described method used in AED analysis is the LC-based technique (HPLC, UHPLC, USLC) combined with highly sensitive mass detection or fluorescence detection. However, less sensitive UV is also used. Capillary electrophoresis and gas chromatography have been rarely applied. Besides the precipitation of proteins or LLE, an automatic SPE is often a sample preparation method. Derivatization was also indicated to improve sensitivity and automate the analysis. The usefulness of the methods for TDM was also highlighted.

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“…Many analytical methods are available for estimating serum topiramate concentrations, including GC [133], HPLC [114], LC/MS [134], and immunoassay [135]. Simultaneous HPLC–MS/MS analysis of topiramate, zonisamide, lamotrigine, carbamazepine, and levetiracetam in serum has been discussed [136]. …”

Section: Newer Antiepileptic Drugsmentioning

confidence: 99%

An Updated Overview on Therapeutic Drug Monitoring of Recent Antiepileptic Drugs

2016

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Given the distinctive characteristics of both epilepsy and antiepileptic drugs (AEDs), therapeutic drug monitoring (TDM) can make a significant contribution to the field of epilepsy. The measurement and interpretation of serum drug concentrations can be of benefit in the treatment of uncontrollable seizures and in cases of clinical toxicity; it can aid in the individualization of therapy and in adjusting for variable or nonlinear pharmacokinetics; and can be useful in special populations such as pregnancy. This review examines the potential for TDM of newer AEDs such as eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, perampanel, pregabalin, rufinamide, retigabine, stiripentol, tiagabine, topiramate, vigabatrin, and zonisamide. We describe the relationships between serum drug concentration, clinical effect, and adverse drug reactions for each AED as well as the different analytical methods used for serum drug quantification. We discuss retrospective studies and prospective data on the serum drug concentration–efficacy of these drugs and present the pharmacokinetic parameters, oral bioavailability, reference concentration range, and active metabolites of newer AEDs. Limited data are available for recent AEDs, and we discuss the connection between drug concentrations in terms of clinical efficacy and nonresponse. Although we do not propose routine TDM, serum drug measurement can play a beneficial role in patient management and treatment individualization. Standardized studies designed to assess, in particular, concentration–efficacy–toxicity relationships for recent AEDs are urgently required.

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Simultaneous Quantitation of Lamotrigine, Levetiracetam, 10-Hydroxycarbazepine, Topiramate, and Zonisamide in Serum Using HPLC-MS/MS

Cited by 16 publications

References 7 publications

Simultaneous determination of four antiepileptic drugs in human plasma samples using an ultra‐high‐performance liquid chromatography tandem mass spectrometry method and its application in therapeutic drug monitoring

Simultaneous determination of four antiepileptic drugs in human plasma samples using an ultra‐high‐performance liquid chromatography tandem mass spectrometry method and its application in therapeutic drug monitoring

New Methods Used in Pharmacokinetics and Therapeutic Monitoring of the First and Newer Generations of Antiepileptic Drugs (AEDs)

An Updated Overview on Therapeutic Drug Monitoring of Recent Antiepileptic Drugs

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