A sensitive gas chromatographic/mass spectrometric method for the resolution and quantification of ethosuximide enantiomers in biological fluids

Antiepileptic drugs—best practice guidelines for therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies

“…Commercial reagent‐based techniques represent the primary methodology for the analysis of ethosuximide in serum (e.g., FPIA and EMIT; Miles et al, 1989). However, there are also GC and HPLC techniques available which have the advantage of simultaneously measuring numerous other AEDs (Matar et al, 1999; Speed et al, 2000; Sghendo et al, 2002; Casas et al, 2004).…”

Chiral chromatographic resolution of antiepileptic drugs and their metabolites: a challenge from the optimization to the application

“…Chemically, it is the R , S ‐2‐ethyl‐2‐methyl‐succinimide (Fig. ), a chiral compound that exists in pharmaceutical preparations as the racemate form (Sghendo et al ., ). Its metabolism in animals, particularly in rats, and humans has been extensively investigated; the animal pre‐clinical investigations were performed not only after the administration of the racemic mixture, as occurred in human studies, but also after the administration of each single enantiomer.…”

“…More recently, two GC-MS techniques were developed for the qualitative (Millership et al, 2005) and quantitative analysis of ethosuximide enantiomers and metabolites (Sghendo et al, 2002). The chromatographic conditions were very similar to those described in the previous paragraph but the MS detector was operated in the electron ionization/scanning mode, collecting data between 30 and 450 mass units for the preliminary qualitative analysis and in the electron ionization/selective-ion monitoring mode, setting the mass-to-charge (m/z) at 55 and 70 units (Sghendo et al, 2002;Millership et al, 2005).…”

“…It is important to highlight that sample (urine and plasma) extraction procedures were common to both GC-FID and GC-MS methodologies and the same internal standard was always utilized (α,α-dimethyl-β-methylsuccinimide). Briefly, after spiking with the internal standard, the biological samples were subjected to a liquid-liquid extraction with diethyl ether two (Mifsud et al, 2001a(Mifsud et al, , 2001bMillership et al, 2005) or three times (Sghendo et al, 2002). The total diethyl ether layers were dried with anhydrous sodium sulfate overnight to precipitate proteins and eliminate other early eluting endogenous substances.…”

Development of a high-throughput method for the determination of ethosuximide in human plasma by liquid chromatography mass spectrometry

“…There are numerous published procedures that describe the quantitation of ethosuximide in plasma or serum. Different analytical methods for determination of ethosuximide as anticonvulsant drug have been reported, including high performance liquid chromatography (HPLC) [5][6][7][8][9][10][11][12][13], HPLC by derivatization [14,15] and gas chromatographic (GC) by chiral method [16,17]. To date only one LC/API-MS procedure has been reported for the quantitation of ethosuximide [18].…”