Simple and validated HPLC–UV analysis of levetiracetam in deproteinized plasma of patients with epilepsy

Contin, Manuela; Mohamed, Susan; Albani, Fiorenzo; Riva, R.; Baruzzi, Agostino

doi:10.1016/j.jchromb.2008.08.007

Cited by 56 publications

(43 citation statements)

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“…Different wavelengths between 205 and 240 nm were tested. Considering that real clinical samples can be difficult to yield chromatographic peak separations because of comedications and endogenous interferences, a high wavelength set at 235 nm showed to be the best for selectivity instead of the UV detection at 205 nm (very unspecific) described elsewhere (Contin et al, 2008;Martens-Lobenhoffer, Bode-Boger, 2005;Pucci et al, 2004;Zufia et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Several chromatographic methods have been published for quantification of LEV concentrations in biological fluids such as saliva and plasma (or serum) for TDM and in urine for pharmacokinetic aims. They include different subtypes of liquid chromatography with various detection systems (Contin et al, 2008;Grim et al, 2003;Guo et al, 2007;Jain et al, 2006;Juenke et al, 2006;Kuhn, Knabbe, 2013;Lancelin et al, 2007;Martens-Lobenhoffer, BodeBoger, 2005;Matar, 2008;Pucci et al, 2004;Rao et al, 2004;Ratnaraj, Doheny, Patsalos, 1996;Shibata et al, 2012), gas chromatography (Isoherranen et al, 2000;Mecarelli et al, 2007) and microemulsion electrokinetic chromatography (Ivanova et al, 2003). An analytical nonchromatographic method, capillary electrophoresis, is also described (Shihabi, Oles, Hinsdale, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Protein precipitation is considered a simple, inexpensive and suitable pretreatment procedure especially for drugs minimally bound to plasma proteins. Preparation usually consists of adding organic solvents such as methanol or acetonitrile; formation of insoluble salts through addition of zinc sulphate or perchloric acid is also possible (Contin et al, 2008;Martens-Lobenhoffer, Bode-Boger, 2005;Pucci et al, 2004). Although dilutions can affect the sensitivity of the method, this procedure is considered a positive pretreatment method because LEV is not significantly bound to plasma proteins (Pucci et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Stir bar-sorptive extraction, solid phase extraction and liquid-liquid extraction for levetiracetam determination in human plasma: comparing recovery rates

Freitas‐Lima

Ferreira

Bertucci

et al. 2015

Braz. J. Pharm. Sci.

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Levetiracetam (LEV), an antiepileptic drug (AED) with favorable pharmacokinetic profile, is increasingly being used in clinical practice, although information on its metabolism and disposition are still being generated. Therefore a simple, robust and fast liquid-liquid extraction (LLE) followed by highperformance liquid chromatography method is described that could be used for both pharmacokinetic and therapeutic drug monitoring (TDM) purposes. Moreover, recovery rates of LEV in plasma were compared among LLE, stir bar-sorptive extraction (SBSE), and solid-phase extraction (SPE). Solvent extraction with dichloromethane yielded a plasma residue free from usual interferences such as commonly co-prescribed AEDs, and recoveries around 90% (LLE), 60% (SPE) and 10% (SBSE). Separation was obtained using reverse phase Select B column with ultraviolet detection (235 nm . The intra-and inter-assay precision and accuracy were studied at three concentrations; relative standard deviation was less than 10%. The limit of quantification was 2.8 µg mL -1 . This robust method was successfully applied to analyze plasma samples from patients with epilepsy and therefore might be used for pharmacokinetic and TDM purposes.Uniterms: Levetiracetam/pharmacokinetic. High performance liquid chromatography. Antiepileptic drugs/therapeutic monitoring. Epilepsy/treatment.Levetiracetam, fármaco antiepiléptico com perfil farmacocinético favorável, tem sido cada vez mais utilizado na prática clínica, embora informações sobre seu metabolismo e disposição cinética ainda estejam sendo geradas. Um método simples, robusto e rápido de extração líquido-líquido seguido por análise por cromatografia líquida de alta eficiência é aqui descrito para servir tanto a investigações farmacocinéticas quanto à monitorização terapêutica. Além disso, as taxas de recuperação do levetiracetam em plasma foram comparadas entre a extração líquido-líquido, a extração sortiva em barra de agitação e a extração em fase sólida. Extração com o solvente diclorometano resultou em plasma livre de interferentes, tais como fármacos antiepilépticos co-prescritos, e apresentou taxas de recuperação em torno de 90% (extração líquido-líquido), 60% (extração em fase sólida) e 10% (extração sortiva em barra de agitação). A separação foi obtida utilizando-se coluna de fase reversa Select B e detecção ultravioleta (235 nm). A fase móvel foi composta por metanol:tampão acetato de sódio 0,125 M pH 4,4 (20:80, v/v). O método mostrou-se linear para o intervalo de 2,8 a 220,0 µg mL -1. Precisão intra-e interdias e a exatidão foram avaliadas em três concentrações; o desvio padrão relativo foi inferior a 10%. O limite de quantificação foi 2.8 µg mL . Este método foi aplicado para análise de amostras de plasma de pacientes com epilepsia e, desta forma, pode ser utilizado satisfatoriamente tanto para fins de farmacocinética quanto de monitorização terapêutica.Unitermos: Levetiracetam/farmacocinética. Cromatografia líquida de alta eficiência. Antiepiléticos/ monitorização terapêutica. Epilepsia/trata...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Stir bar-sorptive extraction, solid phase extraction and liquid-liquid extraction for levetiracetam determination in human plasma: comparing recovery rates

Freitas‐Lima

Ferreira

Bertucci

et al. 2015

Braz. J. Pharm. Sci.

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“…The availability of simple, accurate and inexpensive analytical assays is crucial for the successful use of TDM in clinical practice. LVT spiked plasma sample preparation by different kinds of deproteinization before HPLC-diode array detection was first explored by Pucci et al [184] and subsequently applied to patient samples analysis by HPLC-UV [176,182,186]. Otherwise, these involve GC-NPD [187] and GC-MS [188].…”

Section: Levetiracetam (Lvt)mentioning

confidence: 99%

Modern Methods for Analysis of Antiepileptic Drugs in the Biological Fluids for Pharmacokinetics, Bioequivalence and Therapeutic Drug Monitoring

Kang

Park

Kim

et al. 2011

Korean J Physiol Pharmacol

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“…Diversos métodos han sido reportados para el análisis de Levetiracetam en variados fluidos biológicos, tales como espectrometría de masas (8,9), cromatografía de gases (10) y cromatografía liquida de alta precisión HPLC (11,12,13). En este estudio se ha realizado un método rá-pido y sencillo para la determinación de Levetiracetam en muestras de suero, basado en el método previamente reportado por Martens-Lobenhoffer con algunas modificaciones que lo hacen más sencillo, para ser empleado en estudios farmacocinéticos y se ha validado de acuerdo a los parámetros establecidos por la Oficina de las Naciones Unidas (14) y la FDA (15).…”

Section: Introductionunclassified

Determinación de Levetiracetam en suero mediante HPLC-UV

Sarmiento

2014

Rev. Med.

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ResumenEl Levetiracetam es un medicamento antiepiléptico derivado de la pirrolidona con un mecanismo de acción diferente a otros antiepilépticos, al unirse de forma específica a la proteína SV2A de la vesícula sináptica modulando su actividad. Diversos métodos han sido reportados para el análisis de Levetiracetam en variados fluidos biológicos, siendo la cromatografía líquida de alta precisión HPLC (de la sigla en inglés High Performance Liquid Chromatography) uno de los más utilizados. En este estudio se describe un método rápido y sencillo para la determinación de Levetiracetam en muestras de suero con extracción líquido-líquido, detección ultravioleta a 205 nm, fase móvil isocrática y Captopril como estándar interno, el rango de detección es entre 1 y 100 µg/ml con precisión y exactitud del 95% y un tiempo total de elución de 18 minutos por muestra. El método es lo suficientemente sensible, exacto, y reproductible para ser usado en estudios farmacocinéticos. Palabras clave. HPLC, Levetiracetam, antiepilepticos, farmacocinética LEVETIRACETAM DETERMINATION IN SERUM BY HPLC-UV AbstractLevetiracetam is an antiepileptic medicament derived from the pirrolidona, Its mechanism of action is different from other antiepileptic drugs, by binding specifically in the synaptic vesicle protein SV2A. Diversified methods have been brought to Levetiracetam analysis in varied biological fluids, being the High-Performance Liquid Chromatography (HPLC) one of the most used. In this study a method is described for rapid and simple Levetiracetam determination in serum samples with liquid -liquid extraction, ultraviolet detection to 205 nm, isocratic mobile phase and Captopril as internal standard. The method is linear over the studied range of 1 and 100 µg/ml, with 95% of precision and accuracy and total elution time to 18 min for a sample. This method is highly sensitive, exact and reproducible for be used in pharmacokinetic studies.

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Simple and validated HPLC–UV analysis of levetiracetam in deproteinized plasma of patients with epilepsy

Cited by 56 publications

References 8 publications

Stir bar-sorptive extraction, solid phase extraction and liquid-liquid extraction for levetiracetam determination in human plasma: comparing recovery rates

Stir bar-sorptive extraction, solid phase extraction and liquid-liquid extraction for levetiracetam determination in human plasma: comparing recovery rates

Modern Methods for Analysis of Antiepileptic Drugs in the Biological Fluids for Pharmacokinetics, Bioequivalence and Therapeutic Drug Monitoring

Determinación de Levetiracetam en suero mediante HPLC-UV

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