title: Implementation of a cost-effective HPLC/UV approach for routine medical quantification of memantine in human serum.
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.
  
  
  METHODS
  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 π-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/r² > 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, Clinical Pharmacology/Psychopharmacology, University of Regensburg, Universitätsstrasse 84, D-93055 Regensburg, Germany. ekkehard.haen@klinik.uni-regensburg.de
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Haen
authors.forename: Ralf
authors.initials: R
authors.lastname: Koeber
authors.forename: Hans-Hermann
authors.initials: HH
authors.lastname: Klünemann
authors.forename: Reinhold
authors.initials: R
authors.lastname: Waimer
authors.forename: Anton
authors.initials: A
authors.lastname: Köstlbacher
authors.forename: Markus
authors.initials: M
authors.lastname: Wittmann
authors.forename: Regina
authors.initials: R
authors.lastname: Brandl
authors.forename: Anett
authors.initials: A
authors.lastname: Dörfelt
authors.forename: Tatjana
authors.initials: T
authors.lastname: Jahner
authors.forename: Doris
authors.initials: D
authors.lastname: Melchner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053000:Analytic Sample Preparation Methods; D002851:Chromatography, High Pressure Liquid; D017046:Cost Savings; D003704:Dementia / Q000097:blood / Q000188:drug therapy*; D016903:Drug Monitoring / Q000191:economics; D005858:Germany; D017721:Hospital Costs; D006778:Hospitals, Psychiatric; D006801:Humans; D057230:Limit of Detection; D008297:Male; D008559:Memantine / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D008875:Middle Aged; D018697:Nootropic Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D011619:Psychotropic Drugs / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D015203:Reproducibility of Results; D052616:Solid Phase Extraction; D013056:Spectrophotometry, Ultraviolet
chemical_list: D018697:Nootropic Agents; D011619:Psychotropic Drugs; D008559:Memantine