Validation of liquid-liquid extraction followed by flow-injection negative ion electrospray mass spectrometry assay to Topiramate in human plasma

Abstract

This paper describes the development and validation of a method for the quantitative analysis of Topiramate (2,3:4,5‐bis‐O‐(1‐methylethylidene)‐β‐D‐fructopyranose sulfamate), a new antiepileptic drug, in human plasma using liquid‐liquid extraction followed by flow‐injection negative ion electrospray mass spectrometry. Using Prednisone (1,4‐pregnadiene‐17‐α,21‐diol‐3,11,20‐trione [10 µg/mL]) as an internal standard, calibration curves for Topiramate were linear over a range of 1 to 30 µg/mL in human plasma and were highly reliable (r2 = 0.9991). The lower limit of quantitation of the assay was 2 µg/mL in human plasma. Precision (%CV <15%) and accuracy (<20%) for both intra‐ and inter‐day validations were satisfactory. The method has been used in clinical pharmacology research. Copyright © 2001 John Wiley & Sons, Ltd.

Simple and sensitive high performance liquid chromatography method with fluorescence detection for therapeutic drug monitoring of topiramate

“…For various reasons, including insufficient analytical sensitivity 12,23,24,26,28,29,31,35 and linearity, 24,25,[32][33][34]36 previously reported liquid chromatography techniques coupled with various detection systems can not accurately determine full therapeutic range of TPM concentrations. These methods either lack adequate sensitivity, and consequently cannot be applied in pharmacokinetic studies, or the method range is to narrow and therefore they are not practical for routine TDM.…”

“…5,6,13,14 The availability of a simple, validated and inexpensive analytical method for reliable measurements of drug concentrations in biological fluids is pivotal for its successful utilization in pharmacokinetic and bioequivalence studies, and for therapeutic drug monitoring in various clinical situations. 15 Various analytical methods have been reported for measurement of TPM in biological fluids, including immunoassays, 16,17 gas chromatography (GC) coupled to flame ionization detection (FID) 18 or nitrogen phosphorous detection (NPD), [19][20][21][22] high performance liquid chromatography with UV (HPLC-UV) 23 or fluorescence detection (HPLC-FLD), [24][25][26] capillary electrophoresis with UV detection, 27 liquid chromatography coupled to mass spectrometry (LC-MS), 28,29 and more recently, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). 12,[30][31][32][33][34][35][36] The analysis of TPM in biological fluids is complicated, because like most other carbohydrates and their derivatives, TPM does not contain any chromophores that absorb above 190 nm.…”

Fast LC/MS in the analysis of small molecules

“…(Reproduced with permission from ref. [193] ©John Wiley & Sons Limited) method was amenable to validation [197] indicates that the extraction used, in combination with negative ion mass spectrometry, has enabled the removal of isobaric interferences.…”

Modern Methods for Analysis of Antiepileptic Drugs in the Biological Fluids for Pharmacokinetics, Bioequivalence and Therapeutic Drug Monitoring

“…A commercial reagent-based FPIA method is available for the measurement of TPM in plasma or serum [219,220]. More recently, an improved GLC-NPD method was reported [221] and either GLC or HPLC with MS [222][223][224] and tandem MS detection have developed [221,225].…”