PMID: 12766560May 27, 2003Paper

Analysis of topiramate and its metabolites in plasma and urine of healthy subjects and patients with epilepsy by use of a novel liquid chromatography-mass spectrometry assay

Therapeutic Drug Monitoring
Malka BritziMeir Bialer

Abstract

A novel liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for quantification of topiramate (TPM) and its metabolites 10-hydroxy topiramate (10-OH-TPM), 9-hydroxy topiramate (9-OH-TPM), and 4,5-O-desisopropylidene topiramate (4,5-diol-TPM) in plasma and urine. The method uses 0.5 mL of plasma or 1 mL of urine that is extracted with diethyl ether and analyzed by LC-MS. Positive ion mode detection enables tandem mass spectrometric (MS/MS) identification of the aforementioned four compounds. Calibration curves of TPM, 4,5-diol-TPM, 9-OH-TPM, and 10-OH-TPM in plasma and urine were prepared and validated over the concentration range of 0.625 to 40 microg/mL using TPM-d(12) as an internal standard. Calibration curves were linear over this concentration range for TPM and its metabolites. Accuracy and precision ranged in urine from 83% to 114% and 4% to 13% (%CV), respectively, and in plasma from 82% to 108% and 6% to 13%, respectively. The applicability of the assay was evaluated by analyzing plasma samples from a healthy subject who received a single oral dose of TPM (200 mg) and urine samples from 11 patients with epilepsy treated with TPM (daily dose between 100 to 600 mg) alone or with other antiepi...Continue Reading

References

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Citations

Apr 9, 2010·Journal of Medical Toxicology : Official Journal of the American College of Medical Toxicology·Michael J LynchMatthew D Krasowski
Sep 10, 2004·Clinical Pharmacokinetics·Meir BialerStefan Schwabe
Oct 15, 2013·Clinical Pharmacokinetics·Gail D Anderson, Shahin Hakimian
Jul 20, 2010·Pharmaceuticals·Matthew D Krasowski
Apr 7, 2010·Journal of Pharmaceutical and Biomedical Analysis·Roberto MandrioliMaria Augusta Raggi
Mar 9, 2010·Thérapie·Danièle Bentué-FerrerUNKNOWN le groupe Suivi Thérapeutique Pharmacologique de la Société Française de Pharmacologie et de Thérapeutique
Feb 9, 2010·Clinica Chimica Acta; International Journal of Clinical Chemistry·Kamal M Matar
Nov 5, 2008·Journal of Pharmaceutical and Biomedical Analysis·Giancarlo la MarcaRenzo Guerrini
Jan 2, 2007·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Gholamreza Bahrami, Bahareh Mohammadi
Jul 14, 2009·Biomedical Chromatography : BMC·Dipanjan GoswamiShamsur Rab
Jan 10, 2012·Biomedical Chromatography : BMC·Jeannine M ConwayRory P Remmel
Jul 6, 2005·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Gholamreza BahramiAmir Kiani
Apr 16, 2015·Biomedical Chromatography : BMC·Eduardo Costa PintoValéria Pereira de Sousa
Oct 14, 2011·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Joanne E Adaway, Brian G Keevil
Oct 22, 2016·Drugs in R&D·Shery Jacob, Anroop B Nair
Nov 5, 2003·Journal of Mass Spectrometry : JMS
Apr 29, 2019·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Suresh NarayanasamyMurali K Matta

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