Microemulsion electrokinetic chromatography applied for separation of levetiracetam from other antiepileptic drugs in polypharmacy

Abstract

Microemulsion electrokinetic chromatography was applied for the separation of levetiracetam from other antiepileptic drugs (primidone, phenobarbital, phenytoin, lamotrigine and carbamazepine) that are potentially coadministered in therapy of patients. The influence of the composition of the microemulsion system (with sodium dodecyl sulfate as charged surfactant) was investigated, modifying the kind of cosurfactant (lower alcohols from C3 to C5), the pH (and salinity) of the aqueous background electrolyte, and the ratio of aqueous phase to organic constituents forming the microdroplets of the oil-in-water emulsion. Separation selectivity was depending on all these parameters, resulting even in changes of the migration sequence of the analytes. Only moderate correlation was observed for the microemulsion system compared with a micellar system, both consisting of the aqueous borate buffer (pH 9.2) and SDS as micelle former (linear correlation coefficient for analyte mobilities is 0.974). The sample solvent plays an important role on the shape of the resulting chromatograms: methanol at concentrations higher than 35% impairs peak shape and separation efficiency. The microemulsion method (with 93.76% aqueous borate buffer (pH 9.2, 10 mM), 0.48% n-octane, 1.80% SDS, 3.96% 1-butanol, all w/w) is suitable for the determination of levetiracetam in human plasma (combined with a sample pretreatment based on solid-phase extraction).

High‐performance liquid chromatographic determination of Levetiracetam in human plasma: comparison of different sample clean‐up procedures

“…Only a few papers on the analysis of Levetiracetam in human plasma are reported in the literature, including high-performance liquid chromatographic (Ratnaraj et al, 1996;Vermeij and Edelbroek, 1994) and gas-liquid chromatographic (Vermeij and Edelbroek, 1994;Isoherranen et al, 2000) methods. In a recent work, the determination of Levetiracetam in human plasma is carried out by microemulsion electrokinetic chromatography (Ivanova et al, 2003). For the pretreatment of plasma samples, the previously reported papers use solid-phase extraction procedures employing C 18 cartridges (Vermeij and Edelbroek, 1994;Isoherranen et al, 2000;Ivanova et al, 2003); only one liquid-liquid extraction procedure with dichloromethane is reported (Ratnaraj et al, 1996).…”

Validation of an Automated Assay for Levetiracetam (Keppra) on Vitros 5600

“…Apart from evaluating toxicity, therapeutic drug monitoring for levetiracetam is used in adjusting dosage for renal insufficiency. Numerous analytical methods have been reported in the literature, for measurement of levetiracetam in plasma/serum including high-performance liquid chromatography (HPLC), 3 gas chromatography, gas chromatography-mass spectrometry, LC-MS/MS, microemulsion electrokinetic chromatography, and capillary electrophoresis (18)(19)(20)(21)(22)(23)(24)(25). Previously, method comparison was performed as was comparison of immunoassay; CDx90 platform by Thermo-Fisher Scientific with Agilent 1100 HPLC system was performed using ARK immunoassay to reduce turnaround time and improve patient care (10).…”

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

“…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].…”