title: Therapeutic drug monitoring of levetiracetam: comparison of a novel immunoassay with an HPLC method.
abstract: BACKGROUND
  Therapeutic drug monitoring of the anticonvulsant levetiracetam may be indicated in patients with conditions that may alter pharmacokinetic characteristics, for tailoring individual dosage regimens or to investigate patient compliance. In this study, the Bio-Rad high-performance liquid chromatography (HPLC) method (in-use method) and the ARK immunoassay method (new method) for levetiracetam monitoring in serum were compared.
  
  
  METHODS
  Levetiracetam concentrations were determined in 63 samples using: (1) "Levetiracetam by HPLC" kit by Bio-Rad (Hercules, CA) on the Agilent 1100 HPLC system, and (2) "ARK Levetiracetam" immunoassay by ARK Diagnostics Inc (Fremont, CA) on the CDx90 platform by ThermoFisher Scientific Inc.
  
  
  RESULTS
  Within-laboratory imprecision and bias of the new method evaluated over a 20-day period were 7.4% and 0.5% at 7.5 mcg/mL, 4.5% and 1.9% at 30 mcg/mL, and 3.1% and 2.0% at 75 mcg/mL. Passing-Bablok regression analysis (X:Bio-Rad; Y:Ark) showed a nonsignificant intercept of 0.16 [95% confidence interval (CI), -0.55 to 0.72] and a slope marginally significantly different from unity of 0.95 (95% CI, 0.90-0.99), which suggested minimum proportional systematic error. In agreement, Bland-Altman analysis showed minimum systematic bias of 1.0 mcg/mL (95% CI, 0.32-1.69) with 95% of the HPLC-Ark differences ranging from -4.3 (95% CI, -5.52 to -3.16) to 6.3 (95% CI, 5.16-7.52). Our data showed that the 2 methods were identical both within inherent imprecision and analytical quality specifications (maximum allowable error 15%).
  
  
  CONCLUSIONS
  The new Ark method on the CDx platform is acceptable and may be used to measure serum levetiracetam concentrations routinely.
authors.affiliation: *Laboratory of Toxicology, Santi Antonio e Biagio e Cesare Arrigo Hospital, Alessandria; and †Clinical Chemistry Unit, Maggiore della Carità Hospital, and ‡Department of Health Sciences, University Amedeo Avogadro of East Piedmont, Novara, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Bianchi
authors.forename: Carlo
authors.initials: C
authors.lastname: Arfini
authors.forename: Matteo
authors.initials: M
authors.lastname: Vidali
mesh_terms: D000927:Anticonvulsants / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D000077287:Levetiracetam; D010889:Piracetam / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam