title: High-throughput method for the quantification of lacosamide in serum using ultrafast SPE-MS/MS.
abstract: BACKGROUND
  Lacosamide is an anticonvulsant drug approved for adjunctive therapy of partial-onset seizures in adults. Monitoring serum lacosamide concentrations may be useful in assessing compliance and optimizing therapy. The clinical need for faster turn-around-times and increased testing volumes has led to the desire to develop faster methods of analysis for higher throughput of samples.
  
  
  METHODS
  Fifty microliters of calibration standards, quality controls, and patient samples were precipitated with methanol containing deuterated internal standard. The supernatant was then diluted with aqueous mobile phase and injected on an ultrafast solid-phase extraction-mass spectrometry with a cycle time of <10 seconds per sample.
  
  
  RESULTS
  The analytic linear range for the assay was 0.5-50.0 mcg/mL with a limit of detection of 0.05 mcg/mL. The assay showed interassay and intraassay precision coefficient of variations <7%, with no significant carryover after a sample twice the upper limit of quantitation, and no interference from the top 24 prescribed drugs, other anticonvulsants, or common drugs of abuse. Analytical accuracy was determined by comparing 26 results (19 patients, 7 standards and quality control) with a reference laboratory using liquid chromatography-mass spectrometry in addition to 11 proficiency samples from the LGC Standards Proficiency Testing survey. The results were compared using a standard linear regression with the equation of the line being y = 1.093x - 0.166, with an r(2) = 0.99, and a y intercept 95% confidence interval that included zero.
  
  
  CONCLUSIONS
  Herein, the authors present a method for the quantification of lacosamide in serum with ultrafast solid-phase extraction-mass spectrometry that uses 50 μL of sample, is linear from 0.5 to 50 mcg/mL, has interassay and intraassay coefficient of variations of <7%, and has much faster sample cycle times with similar analytic results compared with traditional liquid chromatography-mass spectrometry.
authors.affiliation: *Toxicology and Drug Monitoring Laboratory; and †Division of Clinical Biochemistry and Immunology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Eric
authors.initials: E
authors.lastname: Korman
authors.forename: Loralie J
authors.initials: LJ
authors.lastname: Langman
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Jannetto
mesh_terms: D000081:Acetamides / Q000097:blood*; D000927:Anticonvulsants / Q000097:blood*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D000078334:Lacosamide; D057230:Limit of Detection; D013058:Mass Spectrometry; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D000078334:Lacosamide