Implementation of a Cost-Effective HPLC/UV Approach for Routine Medical Quantification of Memantine in Human Serum

Haen, Ekkehard and Koeber, Ralf and Kluenemann, Hans-Hermann and Waimer, Reinhold and Koestlbacher, Anton and Wittmann, Markus and Brandl, Regina and Doerfelt, Anett and Jahner, Tatjana and Melchner, Doris (2012) Implementation of a Cost-Effective HPLC/UV Approach for Routine Medical Quantification of Memantine in Human Serum. THERAPEUTIC DRUG MONITORING, 34 (6). pp. 702-712. ISSN 0163-4356, 1536-3694

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Abstract

Background: In the near future, there will be no innovative drug principle for the treatment of dementia. Therefore, optimizing the efficacy of a drug is at present the most promising way to exploit its full pharmacological potential. Method: A high performance liquid chromatography with ultraviolet assay for memantine in serum from demented patients has been developed and validated. The analytical procedure involves offline solid phase extraction cartridges. Because memantine molecules lack chromophoric pi-electrons, a derivatization with dansyl chloride was required for detection by ultraviolet (UV) photometry. Analyses were performed on a Dionex high-performance liquid chromatography system with a Phenomenex Luna Phenyl-Hexyl analytical column and 0.02 mol/L potassium dihydrogen phosphate buffer/acetonitrile (40/60 V/V) as mobile phase at a flow rate of 0.4 mL/min. Dansylated memantine was detected at 218 nm; 2 more ultraviolet wavelengths at 254 nm and 336 nm were used as an overlay-control check. Results: The retention time for dansylated memantine was 17.1 +/- 0.2 minutes. The calibration curve was linear over a concentration range from 5 to 160 ng/mL (n = 8/r(2) > 0.999). The method had an accuracy of >90%. Intra-assay and inter-assay coefficients of variation were <5% and <13%, respectively, at 3 different concentrations. The limit of quantification and the limit of detection were 2.9 ng/mL and 0.8 ng/mL, respectively. Among 100 substances prescribed as comedications in the treatment of dementia only fluvoxamine and zuclopenthixole showed retention times close to dansylated memantine (17.8 minutes and 18.1 minutes, respectively). However, these 2 drugs were removed from patients' specimens during solid-phase extraction sample preparation. Conclusions: The method is applicable under conditions of daily routine as has been demonstrated by application of the method to patient serum samples. The quantification of 29 samples showed that memantine concentrations suggested as "therapeutic" in the literature may only be reached by high doses of memantine.

Item Type: Article
Uncontrolled Keywords: LIQUID-CHROMATOGRAPHIC ASSAY; CONSENSUS GUIDELINES; AMANTADINE; PLASMA; PHARMACOTHERAPY; therapeutic drug monitoring; memantine; HPLC/UV; dose-related reference range; individualized dosage
Subjects: 000 Computer science, information & general works > 020 Library & information sciences
600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Psychiatrie und Psychotherapie
Languages and Literatures > Institut für Information und Medien, Sprache und Kultur (I:IMSK) > Lehrstuhl für Informationswissenschaft
Depositing User: Dr. Gernot Deinzer
Date Deposited: 04 May 2020 05:40
Last Modified: 04 May 2020 05:40
URI: https://pred.uni-regensburg.de/id/eprint/17713

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