Sensitive analytical method for Topiramate in human serum by HPLC with pre-column fluorescent derivatization and its application in human pharmacokinetic studies

Bahrami, Gholamreza; Mirzaeei, S H; Kiani, Amir

doi:10.1016/j.jchromb.2004.09.054

Cited by 36 publications

(40 citation statements)

References 16 publications

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“…Exact blood sampling times were recorded by the laboratory personnel. Immediately after blood draws plasma samples were prepared by centrifugation and stored at Ϫ20°C until assayed.For quantification of topiramate in plasma the HPLC method with fluorescent labelling was adapted from Bahrami et al 15) In brief, 250 ml topiramate plasma samples were extracted with dichloromethane, centrifuged and the organic phase was evaporated to dryness. Dry residues were derivatised with 9-fluorenylmethyl chloroformate in the presence of borate buffer.…”

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confidence: 99%

A Nonlinear Mixed Effects Modelling Analysis of Topiramate Pharmacokinetics in Patients with Epilepsy

Vovk

Jakovljević

Kos

et al. 2010

Biological & Pharmaceutical Bulletin

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Topiramate belongs to the second generation of antiepileptic drugs (AEDs) and has been approved for treatment of adults and children with different kinds of epilepsy as mono or as adjunctive therapy.1,2) The exact mechanism of topiramate action is unknown; however, it is considered that antiepileptic effects are exerted by modulation of voltage-dependent sodium channels, enhancement of g-aminobutyrate (GABA)ergic inhibition on the GABA A receptor, inhibition of carbonic anhydrase isoenzymes, and possibly, through the activity at non-N-methyl-D-aspartate receptors. 1,3,4) The effectiveness of topiramate in adults and children with partial onset and primary generalized seizures was established as initial monotherapy as well as adjunctive treatment. 5)Following oral administration of topiramate, absorption is rapid and almost complete with bioavailability ranging from 81 to 95%. 4,6) Peak plasma concentrations of the drug are reached within 1-4 h after administration. 4,6) Food delays topiramate absorption by approximately 2 h, but the extent of absorption remains unaffected.4) Plasma protein-bound fraction of topiramate varies from 9 to 17%. 4,6) In the dose range 100 to 1200 mg the mean apparent volume of distribution is between 0.6 and 1.0 l/kg. 4,6) In women the volume of distribution is about 50% less than in men, which is attributed to a higher percentage of body fat in women.6) This difference is not considered to be clinically relevant. Over 80% of topiramate is eliminated via the kidneys, predominantly as unchanged drug.6) To date, six trace metabolites formed by glucuronidation, hydroxylation and hydrolysis have been identified in humans. In animal seizure models the metabolites have little or no anticonvulsant activity. 4,6) At steadystate the renal clearance of topiramate is 1.02 l/h 6) and its elimination half-life (t 1/2 ) varies from 20 to 30 h. 1,4) Consequently, the steady-state is being reached in 4 to 8 d.2) Over the dose range 100-800 mg the relationship between topiramate dose and serum concentration is linear in both adults and children. 3,7,8) With the commonly used dosage regimen, serum topiramate concentrations in the range between 16 and 60 mmol/l have been reported.3) A wide range of doses and serum concentrations have been associated with optimal clinical response.3) Topiramate serum concentration was found to correlate with the time to the first seizure, 9) while in the majority of studies no clear relationship between average plasma concentration of topiramate and seizure reduction was found. 6,8,10) Based on these findings, clinical response, rather than blood concentrations is used to guide topiramate dosage adjustments. 1,6) Topiramate pharmacokinetic data mostly come from single dose studies with frequent blood sampling in healthy volunteers as well as from studies with sparse sampling in epileptic patients. However, both types of studies provide little information on inter-and intraindividual variability in pharmacokinetics of topiramate. So far there is no published study with a ...

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confidence: 99%

A Nonlinear Mixed Effects Modelling Analysis of Topiramate Pharmacokinetics in Patients with Epilepsy

Vovk

Jakovljević

Kos

et al. 2010

Biological & Pharmaceutical Bulletin

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“…Chromatographic analysis of VPA and TPM was performed after the derivatization step. The derivatization methods using FMOC-Cl that were described previously [7,8,12,20] were modified and adopted to new procedures of VPA and TPM determination. The proposed schemes of derivatization are presented in Fig.…”

Section: Fig 1 Chemical Structures Of Investigated Drugsmentioning

confidence: 99%

“…There are a lot of methods including HPLC, liquid chromatographymass spectrometry (LC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS), GC, GC-MS, and capillary electrophoresis for the analysis of topiramate (TPM) in biological samples [5][6][7][8][9]. Berry and Patsalos determined TPM in plasma and serum by fluorescence polarization immunoassay [10].…”

Section: Introductionmentioning

confidence: 99%

“…For this reason, analysis of the drug by HPLC with UVvis or fluorescence detections is possible only after derivatization with appropriate reagents. Derivatization of TPM by 4-chloro-7-nitrobenzofurazan (NBD-Cl) [6] or 9-fluorenylmethyl chloroformate (FMOC-Cl) [7,8,11,12] and its analysis in human serum or pharmaceutical formulations by HPLC coupled with UV or fluorescence detections have been reported. HPLC analysis was performed on Zorbax SB-C18 column with eluent containing acetonitrile and aqueous solution of NaH 2 PO 4 with triethylammonium (pH 2.8) (52:48).…”

Section: Introductionmentioning

confidence: 99%

“…There is only one report on derivatization with FMOC-Cl to detect TPM in the brain homogenate samples [9], but authors did not describe any details of the derivatization procedure. Various TPM isolation procedures such as SPE, LLE, and protein precipitation were also applied [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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Determination of selected antiepileptic drugs in mouse brain homogenates by HPLC—DAD

Wróblewski

Petruczynik

Radzik

et al. 2017

Acta Chromatographica

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Summary. Three independent reversed phase high-performance liquid chromatography (HPLC) procedures with diode array detection (DAD) for the analysis of carbamazepine (CBZ), topiramate (TPM), and valproic acid (VPA) have been developed in order to determine drug penetration of the blood-brain barrier. Determination of CBZ was performed on C18 column with mobile phases containing methanol (55%, v/v), acetate buffer at pH 3.5 (20%, v/v), double distilled water (25%, v/v), and 0.025 M L −1 diethylamine (DEA). The mobile phase containing acetonitrile and water (8:2, v/v) or acetonitrile and phosphate-citrate buffer at pH 2.6 (1:1), respectively, for analysis of VPA and TPM was applied. Quantification of carbamazepine was performed at 285 nm without extraction procedure before the analysis. Determination of topiramate and valproic acid was performed using precolumn derivatization with 9-fluorenylmethyl chloroformate (FMOC-Cl). FMOC-Cl is a suitable agent, which reacts with both primary and secondary amines and also with acidic groups. Topiramate was determined at 263 nm and valproic acid at 300 nm. The proposed procedures are simple, not time-consuming, and suitable for the determination of investigated compounds in mouse brain homogenates.

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Bioanalytical LC‐MS/MS method validation for plasma determination of topiramate in healthy Indian volunteers

Goswami¹,

Kumar²,

Khuroo³

et al. 2009

Biomedical Chromatography

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A LC-MS/MS method for plasma topiramate analysis is delineated involving least number of healthy volunteers. Topiramate and amlodipine internal standard (IS) were extracted by simple centrifuge-coupled solid-phase extraction and reverse-phase chromatographic separation was performed on an Ascentis C(18) column. Turbo-spray negative-ion mode multiple-reaction monitoring was selected for mass pair detection at m/z 338.3 --> 78.0 and m/z 407.3 --> 295.5 for analyte and IS respectively. The method showed a dynamic linearity range from 10.4 to 2045.0 ng/mL, lower limit of quantitation achieved at 10.4 ng/mL and finally a mass spectrometric total run time of within 2.5 min for human sample analysis. Bioequivalence was assessed successfully using this fully validated method on 16 fasted Indian male subjects with 25 mg topiramate tablet administration. An appropriate study design describes plasma samples collection up to 216 h post dose in two periods, separated by a 28 day washout period. The challenge of half-life matching for test and reference drug was achieved with 73.43 +/- 9.68 and 73.06 +/- 14.03 h, respectively, and intra-subject coefficient of variation achieved within 11% for AUCs and C(max) evaluated by non-compartmental pharmacokinetic analysis. The results of LCMS topiramate complete method validation supported by pharmacokinetic study have not been published before, and are presented and discussed for the first time in this article.

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Sensitive analytical method for Topiramate in human serum by HPLC with pre-column fluorescent derivatization and its application in human pharmacokinetic studies

Cited by 36 publications

References 16 publications

A Nonlinear Mixed Effects Modelling Analysis of Topiramate Pharmacokinetics in Patients with Epilepsy

A Nonlinear Mixed Effects Modelling Analysis of Topiramate Pharmacokinetics in Patients with Epilepsy

Determination of selected antiepileptic drugs in mouse brain homogenates by HPLC—DAD

Bioanalytical LC‐MS/MS method validation for plasma determination of topiramate in healthy Indian volunteers

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