title: A simple assay for determination of levetiracetam in rat dried blood spots by LC-MS/MS.
abstract: BACKGROUND
  A simple LC-MS/MS method was developed and validated for the quantification of levetiracetam (LEV, Keppra®), a broad-spectrum antiepileptic drug (AED) in rat dried blood spots (DBS). LEV was simply extracted with methanol spiked with adenosine (ADE) as IS before LC-MS/MS analysis. The correlation between the DBS and plasma concentrations of LEV was also determined.
  
  
  RESULTS
  Linearity was from 0.067-60 µg/ml for LEV in DBS samples. The intra- and inter-day accuracy and precision of the assay met validation acceptance criteria. The developed assay was applied to monitor levetiracetam DBS levels in Sprague-Dawley rats after intravenous administration. DBS concentrations were well correlated to the plasma concentrations (R² = 0.9399), as fraction of LEV bound to blood cells remains very constant (0.466 ± 0.041) over a wide concentration range.
  
  
  CONCLUSIONS
  The study illustrated that DBS could be used as alternative matrix for monitoring LEV in preclinical studies.
authors.affiliation: Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543 Singapore.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Luo
authors.forename: Sing Teang
authors.initials: ST
authors.lastname: Kong
authors.forename: Shili
authors.initials: S
authors.lastname: Yang
authors.forename: Bernice Choi Wai
authors.initials: BC
authors.lastname: Chan
authors.forename: Paul C
authors.initials: PC
authors.lastname: Ho
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000097:blood*; D002138:Calibration; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods*; D059788:Dried Blood Spot Testing / Q000295:instrumentation / Q000379:methods*; D000077287:Levetiracetam; D057230:Limit of Detection; D008297:Male; D010889:Piracetam / Q000031:analogs & derivatives* / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000295:instrumentation / Q000379:methods*
chemical_list: D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam