Rapid approach to the quantitative determination of topiramate (2,3 : 4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate) in human plasmaby liquid-liquid extraction and flow-injection negative-ion electrospray mass spectrometry

Topiramate, a sulfamate-substituted monosaccharide (2,3:4,5-bis-O-(1-methyl ethylidene)-beta-D-fructopy-ranose sulfamate), is a new antiepileptic drug, which has been approved for adjunctive therapy in adult patients with part ial-onset seizures, Liquid-liquid extraction followed by flow-injection neg ative-ion electrospray mass spectrometry was evaluated as a means for the q uantitative analysis of Topiramate in human plasma. Prednisone (1,4-pregnad iene-17-alpha,21-diol-3,11,20-trione [15 mu g/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 o f 1 to 30 mu g/mL plasma (signal-to-noise ratio >4) and were highly reliabl e (r(2) = 0.994), This approach offers several advantages: (i) the extracti on of Topiramate from human plasma using chloroform is simple and reproduci ble; (ii) the quantitative determination of Topiramate, in the presence of an internal standard, by blow-injection negative-ion electrospray mass spec trometry with selected-ion recording, is rapid and accurate and does not re quire chromatographic separation; (iii) the assay possesses adequate sensit ivity (2-25 mu g/mL) for the quantitative analysis of Topiramate in plasma from patients, Copyright (C) 1999 John Wiley & Sons, Ltd.