A sensitive gas chromatographic/mass spectrometric method for the resolution and quantification of ethosuximide enantiomers in biological fluids.
A modified specific, sensitive and reproducible chiral gas chromatographic (GC) method for the resolution and quantification of ethosuximide enantiomers in urine and plasma was developed. The samples were extracted by liquid-liquid extraction, using diethylether and the enantiomers were separated and quantified on a chiral gas chromatographic column (25QC2 / CYDEX- beta 0.25). The method involved the use of GC/MS instrumentation for the acquisition of data in the electron impact selective-ion monitoring mode, collecting ions characteristic of both ethosuximide and alpha, alpha - dimethyl - beta - methylsuccinimide, the internal standard and of mass-to-charge ratio (m/z) exactly equal to 55 and 70 units. The limit of quantitation of the method was 2.5 microg/ml for both urine and plasma with both enantiomers. The method proved to be linear, precise and reproducible in the 5-300 microg/ml concentration range for urine samples and in the 10-250 microg/ml concentration range for plasma samples. Future research work envisaged the application of this method in pharmacokinetic and pharmacodynamic studies.
Sghendo
Lino
L
Department of Clinical Pharmacology and Therapeutics, The University of Malta, Msida, MSD 06, Malta.
Mifsud
Janet
J
Ellul-Micallef
Roger
R
Portelli
Joe
J
Millership
Jeff S
JS
D000927:Anticonvulsants / Q000032:analysis* / Q000097:blood / Q000652:urine; D002138:Calibration; D005013:Ethosuximide / Q000032:analysis* / Q000097:blood / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000927:Anticonvulsants; D005013:Ethosuximide