Development and Validation of an Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry Method for the Concurrent Measurement of Gabapentin, Lamotrigine, Levetiracetam, Monohydroxy Derivative of Oxcarbazepine, and Zonisamide Concentrations in Serum in a Clinical Setting

Palte, Michael J.; Basu, Sankha S.; Dahlin, Jayme L.; Gencheva, Ralitsa; Mason, Donald S.; Jarolím, Petr; Petrides, Athena K.

doi:10.1097/ftd.0000000000000516

Cited by 28 publications

(29 citation statements)

References 17 publications

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“…HPLC and UHPLC coupled to tandem mass spectrometry detector (MS/MS) methods have also been described [30][31][32][33][34][35][36][37][38] . These methods have several advantages from the analytical chemical point of view.…”

Section: Discussionmentioning

confidence: 99%

Simple and rapid HPLC-UV methods for gabapentin quantification in human plasma and urine: applicability in pharmacokinetics and drug monitoring

Yamamoto

Benzi

Moraes

2021

Rev. Ciênc. Farm. Básica Apl.

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Aim: We aimed to develop methods to determine gabapentin (GAB) in biological samples using high-performance liquid chromatography (HPLC) with application in pharmacokinetics and therapeutic drug monitoring. Methods: Simple, rapid and efficient HPLC-UV methods to quantify GAB in human plasma and urine were developed and validated for clinical analysis of GAB. The 1fluoro-2,4-dinitrobenzene (FDNB) was used as derivatization agent. For plasma samples, protein precipitation using acetonitrile was performed, before the derivatization reaction. Urine samples were cleaned-up by liquid-liquid extraction with dichloromethane:n-butanol (1:1, v/v) after derivatized. Amlodipine besilate was used as internal standard (IS). Results: Gabapentin and IS were resolved on LiChrospher® C18 RP column and a mixture of 50 mM sodium phosphate buffer (pH 3.9):methanol (27:73, v/v) as mobile phase, at 1.2 mL/min. The methods used small sample volumes, 100 and 50 µL of plasma and urine, respectively. Linearity was obtained in the interval of 0.2-14 µg/mL in plasma and 2-120 µg/mL in urine. Both methods showed to be selective, without carry-over effect, precise, accurate and stable in different conditions. GAB plasma concentration in patients receiving 600 to 3600 mg/day of GAB ranged between 0.40 to 11.94 µg/mL at steady-state. Conclusions: The methods described in this study were simple, rapid and fulfill all validation requirements. They were easily and successfully applied for population pharmacokinetics and therapeutic drug monitoring of GAB in patients with chronic pain.

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Section: Discussionmentioning

confidence: 99%

Simple and rapid HPLC-UV methods for gabapentin quantification in human plasma and urine: applicability in pharmacokinetics and drug monitoring

Yamamoto

Benzi

Moraes

2021

Rev. Ciênc. Farm. Básica Apl.

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“…Chromatographic techniques are now considered the gold standard in TDM for their specificity and robustness, although they require trained personnel, specialized laboratories, and long sample processing times [ 45 , 46 , 47 , 48 , 49 , 50 ]. Several reported procedures in TDM use liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), which can discriminate similar compounds based on their retention times, m / z values of the respective pseudo molecular ion, and fragmentation patterns, thus ensuring great specificity in the identification of the analytes [ 51 , 52 , 53 , 54 ]. Since the 2000s, the LC-MS/MS methods were largely adopted for the quantification of free drug concentrations in biological matrices, mainly in plasma and interstitial fluids, providing sensitive detection and accurate results [ 52 , 53 ].…”

Section: Analytical Tools For the Evaluation Of Asms’ Free Drug Fractionmentioning

confidence: 99%

The Effect of Plasma Protein Binding on the Therapeutic Monitoring of Antiseizure Medications

et al. 2021

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Epilepsy is a widely diffused neurological disorder including a heterogeneous range of syndromes with different aetiology, severity and prognosis. Pharmacological treatments are based on the use, either in mono- or in polytherapy, of antiseizure medications (ASMs), which act at different synaptic levels, generally modifying the excitatory and/or inhibitory response through different action mechanisms. To reduce the risk of adverse effects and drug interactions, ASMs levels should be closely evaluated in biological fluids performing an appropriate Therapeutic Drug Monitoring (TDM). However, many decisions in TDM are based on the determination of the total drug concentration although measurement of the free fraction, which is not bound to plasma proteins, is becoming of ever-increasing importance since it correlates better with pharmacological and toxicological effects. Aim of this work has been to review methodological aspects concerning the evaluation of the free plasmatic fraction of some ASMs, focusing on the effect and the clinical significance that drug-protein binding has in the case of widely used drugs such as valproic acid, phenytoin, perampanel and carbamazepine. Although several validated methodologies are currently available which are effective in separating and quantifying the different forms of a drug, prospective validation studies are undoubtedly needed to better correlate, in real-world clinical contexts, pharmacokinetic monitoring to clinical outcomes.

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“…The analytes were determined in biological matrices such as: Plasma [55,66,67,[73][74][75][76][77], serum [78], urine [79], dried blood spot [37]. The methods differ in the sample preparation technique and include liquid-liquid extraction (LLE) [55], salting assisted liquid-liquid extraction (SALLE) [50], SAEME, SPE [73,75,76], micro-extraction by MEPS [66] and deproteinization [67,73,74,77,78].…”

Section: Oxcarbazepinementioning

confidence: 99%

“…Analytical methods reported for the analysis of OXC include, HPLC with UV or DAD detection, and reverse elution on C18 chromatographic column [66,[73][74][75]. The LC, HPLC and HPTLC methods often are coupled with a triple quadrupole mass spectrometer operated in electrospray ionization [67,[76][77][78]. The most frequently used analytical method is HPLC with isocratic elution of mobile phase, and UV or DAD detection [66,[73][74][75].…”

Section: Oxcarbazepinementioning

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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Development and Validation of an Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry Method for the Concurrent Measurement of Gabapentin, Lamotrigine, Levetiracetam, Monohydroxy Derivative of Oxcarbazepine, and Zonisamide Concentrations in Serum in a Clinical Setting

Abstract: A simple, cost-effective, and robust ultra-performance liquid chromatography-tandem mass spectrometry method for monitoring multiple AEDs was developed and validated to address the clinical needs of patients at our institution.

Cited by 28 publications

References 17 publications

Simple and rapid HPLC-UV methods for gabapentin quantification in human plasma and urine: applicability in pharmacokinetics and drug monitoring

Simple and rapid HPLC-UV methods for gabapentin quantification in human plasma and urine: applicability in pharmacokinetics and drug monitoring

The Effect of Plasma Protein Binding on the Therapeutic Monitoring of Antiseizure Medications

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

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