Determination of Lamotrigine and its Metabolites in Human Plasma by Liquid Chromatography-Mass Spectrometry

Beck, Olof; Öhman, Inger; Nordgren, Helena

doi:10.1097/01.ftd.0000245779.64080.30

Cited by 52 publications

(48 citation statements)

References 27 publications

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“…plasma of patients. The proposed HPLC method is simpler and more precise than the HPLC method in the literature which used gradient elution [13]; moreover, the present method gives a more rapid chromatographic analysis (10 min instead of 17 min) than gradient elution chromatography. It is a feasible procedure based on deproteinization with methanol and grants appropriate sample purification and good extraction yields with satisfactory precision.…”

Section: Application To Patient Plasmamentioning

confidence: 92%

“…Only three papers describe the determination of LTG and its metabolites in biological fluids by means of an MEKC [18], an automated sequential trace enrichment of dialysates HPLC [19], and of an HPLC-MS [15]. The pretreatment of biological samples is usually carried out by means of deproteinization by solvents [2,13,15,16], liquid -liquid extraction [14], and SPE [17,18]. The aim of this study was the development of an easy and reliable HPLC method with diode array detection (DAD) for the simultaneous analysis of LTG and its 2-N-glucuronide and 2-N-methylated metabolites in human plasma from patients using a rapid sample pretreatment procedure.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Rapid HPLC analysis of the antiepileptic lamotrigine and its metabolites in human plasma

Saracino¹,

Bugamelli²,

Conti³

et al. 2007

J of Separation Science

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A liquid chromatographic method with diode array detection (DAD) has been developed for the analysis of the antiepileptic agent lamotrigine (LTG) and its metabolites, lamotrigine 2-N-glucuronide and 2-N-methylated in plasma samples. The analytes were separated on a C8 RP column, using a mobile phase composed of methanol and a 0.45 mM, pH 3.5 phosphate buffer containing 0.17% triethylamine (24:76 v/v). Melatonin was used as the internal standard (IS). The DAD detector was set at 220 nm for the detection of all the analytes. A simple protein precipitation with methanol guaranteed high extraction yield values (>90%) and good purification from matrix interference. Good linearity was obtained in the 0.1-15.0 microg/mL range for LTG and lamotrigine 2-N-glucuronide and in the 0.1-2.0 microg/mL range for lamotrigine 2-N-methylated. The analytical method was validated in terms of precision, extraction yield, and accuracy. These assays gave RSD% values for precision always lower than 4.3% and mean accuracy higher than 80%. The method seems to be suitable for the analysis of plasma samples from patients treated with Lamictal.

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Section: Application To Patient Plasmamentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Rapid HPLC analysis of the antiepileptic lamotrigine and its metabolites in human plasma

Saracino¹,

Bugamelli²,

Conti³

et al. 2007

J of Separation Science

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show abstract

“…Lastly, there is a fairly clear concentration threshold above which toxic side effects become more common [90,91]. Multiple analytical methodologies have been reported for the measurement of lamotrigine in plasma/serum including HPLC [92,93,94], radioimmunoassay [95], homogeneous immunoassay [96], immunofluorometric assay [97], capillary electrophoresis [98], capillary zone electrophoresis-electrospray ionization-mass spectrometry [99], gas chromatography (GC) with a nitrogen-phosphorus detector [100], GC/MS [101], LC/MS [102], LC/MS/MS [103] and micellar electrokinetic capillary chromatography [104]. …”

Section: Lamotriginementioning

confidence: 99%

Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

Krasowski

2010

Pharmaceuticals

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In the past twenty years, 14 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. In general, the clinical utility of therapeutic drug monitoring has not been established in clinical trials for these new anticonvulsants, and clear guidelines for drug monitoring have yet to be defined. The antiepileptic drugs with the strongest justifications for drug monitoring are lamotrigine, oxcarbazepine, stiripentol, and zonisamide. Stiripentol and tiagabine are strongly protein bound and are candidates for free drug monitoring. Therapeutic drug monitoring has lower utility for gabapentin, pregabalin, and vigabatrin. Measurement of salivary drug concentrations has potential utility for therapeutic drug monitoring of lamotrigine, levetiracetam, and topiramate. Therapeutic drug monitoring of the new antiepileptic drugs will be discussed in managing patients with epilepsy.

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“…These include radioimmunoassay, [3] high perfor-mance liquid chromatography (HPLC) methods with ultra-violet detection, [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] capillary electrophoresis, [22] gas chromatography-mass spectrometry (GC-MS), [23] electro-spray ionization-mass spectrometry (ESI-MS). [24,25] These conventional quantitative HPLC methods with classical ultra-violet or capillary electrophoresis detection provide insufficient sensitivity and longer chromatographic run time.…”

Section: Introduction Fig 1: Chemical Structure Of Lamotriginementioning

confidence: 99%

Development and Validation of Analytical Method for the Estimation of Lamotrigine in Human Plasma

Kumar¹

2017

WJPPS

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A Simple, rapid, selective and sensitive liquid chromatographic mass spectrometry method was developed and validated for the determination of Lamotrigine from human plasma. The drug was extracted by ethyl acetate. Lamotrigine was measured in plasma using a validated method with mass spectrometer detector. Chromatographic peaks were separated on 4μm Chromolith, RP C-18 (504.6mm, 4µ) using 80:20 v/v Phosphate buffer pH 2.5, Acetonitrile asmobile phase at a flow rate of 0.500 ml/min. The chromatograms showed good resolution and no interference from plasma. The mean recovery from human plasma was found to be above 85%. The method was linear over the concentration range of 5 μg/ml to 1200 μg/ml with coefficient of correlation (r2) 0.9987. Both intraday and interday accuracy and precision data showed good reproducibility. This method was successfully applied to pharmacokinetics studies.

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Determination of Lamotrigine and its Metabolites in Human Plasma by Liquid Chromatography-Mass Spectrometry

Cited by 52 publications

References 27 publications

Rapid HPLC analysis of the antiepileptic lamotrigine and its metabolites in human plasma

Rapid HPLC analysis of the antiepileptic lamotrigine and its metabolites in human plasma

Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

Development and Validation of Analytical Method for the Estimation of Lamotrigine in Human Plasma

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