Determination of levetiracetam in human plasma/serum/saliva by liquid chromatography-electrospray tandem mass spectrometry

Guo, Tiedong; Oswald, Lisa; Mendu, Damodara Rao; Soldin, Steven J.

doi:10.1016/j.cca.2006.06.022

Cited by 72 publications

(50 citation statements)

References 13 publications

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“…For drugs with active metabolites (e.g., oxcarbazepine, primidone), TDM can include measurement of the concentrations of both parent drug and its metabolite(s) or just of the metabolite(s). TDM of AEMs in saliva has not yet been widely applied (Liu & Delgado, 1999), but has been studied for ten drugs: carbamazepine (Ruiz et al, 2010;Tennison et al, 2004), gabapentin (Benetello et al, 1997;Berry et al, 2003), lamotrigine (Incecayir et al, 2007;Malone et al, 2006;Ryan et al, 2003), levetiracetam Guo et al, 2007;Mecarelli et al, 2007), oxcarbazepine (Cardot et al, 1995), phenobarbital (Tennison et al, 2004), phenytoin (Tennison et al, 2004), topiramate ), valproic acid (al Za'abi et al, 2003, and zonisamide (Kumagai et al, 1993). Of these ten drugs, gabapentin and valproic acid are clearly unsuited for salivary concentration analysis.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Drug Monitoring of Antiepileptic Medications

Krasowski¹

2011

Novel Treatment of Epilepsy

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Section: Introductionmentioning

confidence: 99%

Therapeutic Drug Monitoring of Antiepileptic Medications

Krasowski¹

2011

Novel Treatment of Epilepsy

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“…Moreover, this spectroscopic technique is (routinely) used to investigate the photosenzing properties of drugs [50], to identify their possible polymorphic forms [33] or to study the pharmacokinetic and pharmacodynamic properties of drugs in patients [51][52][53]. For these reasons, a reliable assignment of experimental electronic absorption data is highly needed, which in this study is given in terms of IMT monomeric structures.…”

Section: Introductionmentioning

confidence: 99%

Conformational landscape and low lying excited states of imatinib

et al. 2015

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The conformational changes of imatinib (IMT) are crucial for understanding the ligand-receptor interaction and its mechanism of action [Agofonov et al. (2014) Nature Struct Mol Biol 21:848-853]. Therefore, here we investigated the free energy conformational landscape of the free IMT base, aiming to describe the three-dimensional structures and energetic stability of its conformers. Forty-five unique conformers, within an energy window of 4.8 kcal mol −1 were identified by a conformational search in gas-phase, at the B3LYP/6-31G(d) theoretical level. Among these, the 20 most stable, as well as 4 conformers resulting from optimization of experimental structures found in the two known polymorphs of IMT and in the cAbl complex were further refined using the 6-31+G(d,p) basis set and the polarizable continuum solvation model. The most stable conformers in gas-phase and water exhibit a V-shaped structure. The major difference between the most stable free conformers and the bioactive conformers consists in the relative orientation of the pyrimidine-pyridine groups responsible for hydrogen bonding interactions in the ATP-binding pocket.The ratio of mole fractions corresponding to the two known (α and β) polymorphic forms of IMT was estimated from the calculated thermochemical data, in quantitative agreement with the existing experimental data related to their solubility. The electronic absorption spectrum of this compound was investigated in water and explained based on the theoretical TD-DFT results, considering the Boltzmann populationaveraged computed data at CAM-B3LYP/6-31+G(d,p) level of theory for the nine most stable conformers.

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“…There are numerous HPLC techniques [9][10][11][12][13][14][15][16], however there are few reported methods for the analysis of LEV using LC-MS/MS [17][18][19][20]. Two of which utilize a tedious solid phase extraction (SPE) procedure of sample extraction [17,19]. The objective of the present report was to develop and validate a suitable LC-Tandem mass method for moderate throughput as in clinical or commercial reference laboratories for therapeutic drug monitoring of LEV.…”

Section: Introductionmentioning

confidence: 99%

“…Most of these methods are utilized different chromatographic techniques such as Gas chromatography (GC) with nitrogen-phosphorus detection, High performance liquid chromatography (HPLC) and GC-MS [7,8]. There are numerous HPLC techniques [9][10][11][12][13][14][15][16], however there are few reported methods for the analysis of LEV using LC-MS/MS [17][18][19][20]. Two of which utilize a tedious solid phase extraction (SPE) procedure of sample extraction [17,19].…”

Section: Introductionmentioning

confidence: 99%

Novel contribution in online sample cleanup for quantitative determination of Levetiracetam in human plasma by LC-Tandem mass spectrometry

Mostafa

2016

Eur. J. Chem.

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The aim of this work was to develop and validate a simple, sensitive and rapid method for the quantitation of levetiracetam (LEV) in plasma using LC-Tandem mass spectrometry. Plasma samples were prepared by simple protein precipitation using acetonitrile; atenolol was used as internal standard (IS). Chromatographic separation was done on Luna 5 µm C18(2) (Phenomenex) 50 × 2.0 mm using gradient flow using solvent A (0.1% formic acid) and solvent B (0.1% formic acid in acetonitrile: water, 95:5, v:v). The positive-ion mass spectrometric detection method utilized electrospray ionization and the multiple reaction monitoring (MRM) mode. The MRM ion transitions were170.9 → 140.8 and 267.3 → 145.1 for levetiracetam and atenolol, respectively. The retention time of levetiracetam and atenolol is 3.24 and 2.96 min, respectively. The total run time was 5 min. The assay was validated over a concentration range from 1 to 100 µg/mL. The method was robust (minimal matrix effect), sensitive (LOQ, 1 µg/mL) metabolites and reproducible (The precision and accuracy for both intra-and inter-day were acceptable <15%). The method can be done on traditional LC-MS equipment. The method was effectively applied to single case study receiving toxic dose of LEV. KEYWORDS

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Determination of levetiracetam in human plasma/serum/saliva by liquid chromatography-electrospray tandem mass spectrometry

Cited by 72 publications

References 13 publications

Therapeutic Drug Monitoring of Antiepileptic Medications

Therapeutic Drug Monitoring of Antiepileptic Medications

Conformational landscape and low lying excited states of imatinib

Novel contribution in online sample cleanup for quantitative determination of Levetiracetam in human plasma by LC-Tandem mass spectrometry

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