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 and Haen, Ekkehard (2012) Implementation of a cost-effective HPLC/UV-approach for medical routine quantification of donepezil in human serum. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 881-82. pp. 1-11. ISSN 1570-0232,
Full text not available from this repository. (Request a copy)Abstract
A novel, simple, specific and sensitive high performance liquid chromatography (HPLC) assay for the detection and quantification of donepezil in serum of demented patients has been developed and validated. The analytical procedure involves an offline serum preextraction using solid phase extraction (SPE) cartridges (Oasis (R) HLB, Waters Co). The chromatographic analyses were performed on a Dionex HPLC system with a Phenomenex Luna Phenyl-Hexyl analytical column, and a mobile phase with the two components 0.02 mol/I phosphate buffer and acetonitrile. The flow rate was 0.4 ml/min. For the detection of donepezil three different UV wavelengths were used as an interference-control check. Interference tests between donepezil and 100 of the most commonly used concomitant medications allow quantification of donepezil under the polypharmaceutical conditions of the daily clinical routine. The retention time for donepezil was 12.1 min. The method was validated according to the guidelines of the Society of Toxicology and Forensic Chemistry (GTFCh): The calibration curve was linear over a concentration range from 5 to 160 ng/ml (n = 8/r(2) > 0.999). No endogenous compounds were found to interfere with the analyte, which was shown by retention times for the comedication most often prescribed to demented patients. The method had an accuracy of >85%. Intra- and inter-assay coefficients of variation were <6% and <8%, respectively, at three different concentrations. The limit of quantification (LOQ) and the limit of detection (LOD) were found to be 6.1 and 1.7 ng/ml for donepezil. Application of the method to patient serum samples discovered that concentrations suggested as "therapeutic" in the literature may only be reached either by high, off-label dosages or by utilization of inhibitory metabolic effects of the comedication. (C) 2011 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PERFORMANCE LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; HYDROCHLORIDE; COLUMN; PLASMA; TDM; CONSENSUS; Analytical methods; Dose-related reference range; Individualized dosage; Therapeutic drug monitoring (TDM); Antidementia drugs; Donepezil |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 May 2020 09:42 |
| Last Modified: | 20 May 2020 09:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19367 |
Actions (login required)
 |
View Item |
