title: Rapid measurement of tacrolimus in whole blood by paper spray-tandem mass spectrometry (PS-MS/MS).
abstract: BACKGROUND
  Liquid chromatography-tandem mass spectrometry (LC-MS/MS) provides sensitivity and specificity for monitoring tacrolimus drug level in blood, but it requires an LC system and sample preparation, which is not amenable to random access testing typical of immunoassays. Paper spray (PS) ionization generates gas phase analyte ions directly from dried blood spots without sample preparation and LC. We evaluated a PS-MS/MS method for tacrolimus drug monitoring in a clinical diagnostic laboratory.
  
  
  METHODS
  Whole blood sample was mixed with stable isotope labeled internal standard ([(13)C, (2)H2]-FK506) and spotted onto a cartridge containing triangular shaped card paper. After drying, samples were analyzed by PS MS/MS in the selected reaction monitoring (SRM) mode, with a run time of 3 min/sample.
  
  
  RESULTS
  Analytical measurement range was 1.5-30 ng/ml. Assay inter-day imprecision was 13%, 8%, and 5% at tacrolimus concentrations of 4.5, 10.5, and 24.5 ng/ml, respectively. Accuracy was determined by pure tacrolimus solution and was confirmed by result correlation to an immunoassay (slope=1.0, intercept=-0.02; r(2)=0.99), and to a conventional LC-MS/MS method (slope=0.90, intercept=0.4; r(2)=0.94).
  
  
  CONCLUSIONS
  PS-MS/MS provides accurate results for tacrolimus with rapid turnaround time amenable to random access testing protocols.
authors.affiliation: Stanford University School of Medicine, Palo Alto, CA, United States.
authors.forename: Run-Zhang
authors.initials: RZ
authors.lastname: Shi
authors.affiliation: Stanford Hospital & Clinics, Palo Alto, CA, United States.
authors.forename: El Taher M
authors.initials: el TM
authors.lastname: El Gierari
authors.affiliation: Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN, United States. Electronic address: nmanicke@iupui.edu.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Manicke
authors.affiliation: Stanford University School of Medicine, Palo Alto, CA, United States.
authors.forename: James D
authors.initials: JD
authors.lastname: Faix
mesh_terms: D016903:Drug Monitoring; D006801:Humans; D010209:Paper; D016559:Tacrolimus / Q000097:blood*; D053719:Tandem Mass Spectrometry
chemical_list: D016559:Tacrolimus
keywords: Chronogram; DBS; Dried blood spot; Paper spray; TDM; Tandem mass spectrometry