title: Development and validation of a HPLC-UV method for the quantification of antiepileptic drugs in dried plasma spots.
abstract: BACKGROUND
  Therapeutic drug monitoring (TDM) of antiepileptic drugs is widely used in clinical practice to optimise therapy, but it is limited by technical problems and cost considerations. The aim of the present study was: 1) to validate a chromatographic method for the concomitant determination of levetiracetam, lamotrigine, ethosuximide, felbamate, rufinamide, zonisamide and monohydroxycarbamazepine; 2) to develop it for dried plasma spot (DPS) assessing its reliability against the classical determination from plasma; and 3) test its clinical application.
  
  
  METHODS
  Extraction of plasma samples and DPS was done by simple precipitation. Chromatographic analysis was performed using high performance liquid chromatography with ultraviolet detection. After validation, both methods were applied for the quantification of plasma samples from patients on antiepileptic therapy.
  
  
  RESULTS
  Mean inter- and intra-day accuracy and precision were <15% for all compounds both in plasma and in DPS samples. DPS samples were considered stable under tested conditions. Measurements between plasma and DPS samples appeared related (p<0.0001). Bland-Altman analysis revealed accordance in lamotrigine values with mean overestimation of concentration for DPS sample of 2.8%. Also for monohydroxycarbamazepine data the agreement was acceptable (mean overestimation of 9.2%). For levetiracetam mean difference was 7.6%, while for ethosuximide mean percentage difference was 20.6%.
  
  
  CONCLUSIONS
  The developed methods simplify TDM of antiepileptic drugs. This is particularly relevant for the method on dried spot sample devices because it facilitates further sample handling, stability and shipments making the management of therapies in epileptic patients easier also in hospitals devoid of a dedicated laboratory.
authors.forename: Sara
authors.initials: S
authors.lastname: Baldelli
authors.forename: Dario
authors.initials: D
authors.lastname: Cattaneo
authors.forename: Luciana
authors.initials: L
authors.lastname: Giodini
authors.forename: Lorena
authors.initials: L
authors.lastname: Baietto
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
authors.forename: Emilio
authors.initials: E
authors.lastname: Clementi
mesh_terms: D000927:Anticonvulsants / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000592:standards*; D059788:Dried Blood Spot Testing / Q000379:methods* / Q000592:standards; D016903:Drug Monitoring / Q000379:methods* / Q000592:standards; D006801:Humans; D014466:Ultraviolet Rays
chemical_list: D000927:Anticonvulsants