Rapid approach to the quantitative determination of topiramate (2, 3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate) in human plasma by liquid-liquid extraction and flow-injection negative-ion electrospray mass spectrometry.
Topiramate, a sulfamate-substituted monosaccharide (2,3:4, 5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate), is a new antiepileptic drug, which has been approved for adjunctive therapy in adult patients with partial-onset seizures. Liquid-liquid extraction followed by flow-injection negative-ion electrospray mass spectrometry was evaluated as a means for the quantitative analysis of Topiramate in human plasma. Prednisone (1,4-pregnadiene-17-alpha, 21-diol-3,11,20-trione [15 microg/mL]) was used as the internal standard because its solubility and molecular weight are similar to those of Topiramate. Calibration curves for Topiramate were linear over a range of 1 to 30 microg/mL plasma (signal-to-noise ratio >4) and were highly reliable (r(2) = 0.994). This approach offers several advantages: (i) the extraction of Topiramate from human plasma using chloroform is simple and reproducible; (ii) the quantitative determination of Topiramate, in the presence of an internal standard, by flow-injection negative-ion electrospray mass spectrometry with selected-ion recording, is rapid and accurate and does not require chromatographic separation; (iii) the assay possesses adequate sensitivity (2-25 microg/mL) for the quantitative analysis of Topiramate in plasma from patients.
Chen
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Rush Pharmacology Analytical Laboratory Services, Department of Pharmacology, Rush-Presbyterian-St. Luke's Medical Center, 2242 W. Harrison Street, Suite 260, Chicago, IL 60612, USA.
Carvey
P M
PM
D000927:Anticonvulsants / Q000097:blood*; D002725:Chloroform; D005632:Fructose / Q000031:analogs & derivatives* / Q000097:blood; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D011786:Quality Control; D015203:Reproducibility of Results; D000077236:Topiramate
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose; D002725:Chloroform