Determination of Levetiracetam in Human Plasma by Dispersive Liquid-Liquid Microextraction Followed by Gas Chromatography-Mass Spectrometry.

Greyce Kelly Steinhorst Alcantara,Leandro Augusto Calixto,Cristiane Masetto De Gaitani,Luiz Alberto Beraldo De Moraes,Anderson Rodrigo Moraes De Oliveira,Regina Helena Costa Queiroz

doi:10.1155/2016/5976324

Abstract

Levetiracetam (LEV) is an antiepileptic drug that is clinically effective in generalized and partial epilepsy syndromes. The use of this drug has been increasing in clinical practice and intra- or -interindividual variability has been exhibited for special population. For this reason, bioanalytical methods are required for drug monitoring in biological matrices. So this work presents a dispersive liquid-liquid microextraction method followed by gas chromatography-mass spectrometry (DLLME-GC-MS) for LEV quantification in human plasma. However, due to the matrix complexity a previous purification step is required. Unlike other pretreatment techniques presented in the literature, for the first time, a procedure employing ultrafiltration tubes Amicon® (10 kDa porous size) without organic solvent consumption was developed. GC-MS analyses were carried out using a linear temperature program, capillary fused silica column, and helium as the carrier gas. DLLME optimized parameters were type and volume of extraction and dispersing solvents, salt addition, and vortex agitation time. Under chosen parameters (extraction solvent: chloroform, 130 μL; dispersing solvent: isopropyl alcohol, 400 μL; no salt addition and no vortex agitation time), the method was completely validated and all parameters were in agreement with the literature recommendations. LEV was quantified in patient's plasma sample using less than 550 μL of organic solvent.

Highlights

Levetiracetam (LEV; Figure 1(a)) belongs to a generation of antiepileptic drugs that have been recommended for the treatment of epilepsy as either monotherapy in the case of partial seizures or as an adjunctive therapy for partial, myoclonic, and tonic-clonic seizures [1,2,3]
Previously reported methods are mainly based on the conventional sample preparation procedure such as liquid-liquid extraction (LLE), solid-phase extraction (SPE), and plasmatic protein precipitation (PPP) [9,10,11,12,13,14,15,16,17,18,19,20,21,22,23]
No method has been described in the literature for the quantification of LEV from human plasma by gas chromatography (GC)-MS

Summary

Introduction

Levetiracetam (LEV; Figure 1(a)) belongs to a generation of antiepileptic drugs that have been recommended for the treatment of epilepsy as either monotherapy in the case of partial seizures or as an adjunctive therapy for partial, myoclonic, and tonic-clonic seizures [1,2,3]. According to the Subcommittee of the International League Against Epilepsy, the therapeutic plasmatic concentration of LEV was set from 12 to 46 mg L−1 [5, 8]. O NH2 (b) people, pediatric populations, pregnant patients, and patients with renal impairment. These situations could modify the expected plasma concentration, which may lead to a higher and toxic level of LEV [5]

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Conclusion