title: Standardization of LC-MS for therapeutic drug monitoring of tacrolimus.
abstract: BACKGROUND
  LC-MS is increasingly used for therapeutic drug monitoring of tacrolimus. A recent summary from an international proficiency-testing scheme demonstrated that the mass spectrometry respondents were the largest method group. However, these methods lack standardization, which may explain the relatively poor interlaboratory agreement for such methods. This study aimed to provide one path toward the standardization of tacrolimus quantification by use of LC-MS.
  
  
  METHODS
  A 40-member whole blood tacrolimus proficiency panel was circulated to 7 laboratories, 4 in the US and 3 in Europe, offering routine LC-MS-based quantification of tacrolimus. All laboratories used a common LC-MS platform and followed the manufacturer's instructions that accompanied an LC-MS reagent kit intended for tacrolimus quantification in whole blood samples. Four patient pools were prepared that had sufficient volume to allow comparison with a tacrolimus reference measurement procedure.
  
  
  RESULTS
  For the 40-member panel, the standardized MassTrak LC-MS assay demonstrated excellent agreement with a validated LC-MS method used by Analytical Services International (y = 1.02x - 0.02; r = 0.99). The CVs for the pooled patient samples ranged from 2.0% to 5.4%. The mean difference from the reference measurement procedure ranged from 0.4% to 4.4%.
  
  
  CONCLUSIONS
  Tacrolimus assay standardization, which must include all facets of the analysis, is necessary to compare patient results between laboratories and to interpret consensus guidelines. LC-MS can provide accurate and precise measurement of tacrolimus between laboratories.
authors.affiliation: University of Michigan, Ann Arbor, MI;
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Annesley
authors.forename: Denise A
authors.initials: DA
authors.lastname: McKeown
authors.forename: David W
authors.initials: DW
authors.lastname: Holt
authors.forename: Christopher
authors.initials: C
authors.lastname: Mussell
authors.forename: Elodie
authors.initials: E
authors.lastname: Champarnaud
authors.forename: Leonie
authors.initials: L
authors.lastname: Harter
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Calton
authors.forename: Donald S
authors.initials: DS
authors.lastname: Mason
mesh_terms: D002853:Chromatography, Liquid / Q000592:standards*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000592:standards / Q000627:therapeutic use*; D059021:Laboratory Proficiency Testing; D012015:Reference Standards; D016559:Tacrolimus / Q000592:standards / Q000627:therapeutic use*; D053719:Tandem Mass Spectrometry / Q000592:standards*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus