title: Simultaneous detection of 19 drugs of abuse on dried urine spot by liquid chromatography-tandem mass spectrometry.
abstract: BACKGROUND
  The lack of specificity of immunoassays for drugs of abuse testing (DAT), and concerns over its cost in conjunction with reflex confirmatory tests prompted us to investigate the combinatorial use of dried urine spot (DUS) and LC-MS/MS as an alternative.
  
  
  METHODS
  The method development and validation were performed in accordance with the guidelines published by FDA and CLSI.
  
  
  RESULTS
  In this study we established and validated the precision, accuracy, and linearity of our DUS-LC-MS/MS method, and assessed the recovery, interference, and carryover as well. The linearity check for all 19 analytes demonstrated slopes between 0.94 and 1.04, and R(2) always greater than 0.99. Between-batch CV for QC at 4 difference levels ranged from 1.1% to 10%, where CV of LLOQ ranged from 1.2% to 12.8% and CV of ULOQ ranged from 0.8% to 5.1%. A concordance study with patient specimens between our method and GC-MS demonstrated 80.8% to 100% agreement. Stability of DUS specimens was assessed up to 30 days and the measured concentrations ranged from 94% to 114% of the 100 ng/mL urine calibrator used for this assessment.
  
  
  CONCLUSIONS
  We established and validated a DUS-LC-MS/MS method for DAT that conforms to the guidelines dictated by FDA, CLSI, and SAMHSA. While our method with high sensitivity and specificity provides an alternative diagnostic utility to EMIT immunoassays, it also offers superior solutions in specimen transportation, preservation, and storage. The benefits of our method are apparent in reducing turnaround time and test costs that result in better patient care.
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States. Electronic address: hugolee@alumni.usc.edu.
authors.forename: Yungkang
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States; Department of Pathology, University of Southern California, Los Angeles, CA 90033, United States; Southern California Research Center for ALPD and Cirrhosis, University of Southern California, Los Angeles, CA 90033, United States; USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, United States.
authors.forename: Keane K Y
authors.initials: KKY
authors.lastname: Lai
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States. Electronic address: hossein.sadrzadeh@cls.ab.ca.
authors.forename: S M Hossein
authors.initials: SMH
authors.lastname: Sadrzadeh
mesh_terms: D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D013287:Illicit Drugs / Q000652:urine*; D057230:Limit of Detection; D011786:Quality Control; D015203:Reproducibility of Results; D015813:Substance Abuse Detection / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D013287:Illicit Drugs
keywords: CLSI; CV; Clinical and Laboratory Standards Institute; Cost analysis; Cross-reactivity; DAT; DUS; EMIT; Extraction; FDA; Food and Drug Administration; GC–MS; LC–MS/MS; LLOQ; QC; Reflex GC–MS; SAMHSA; Substance Abuse and Mental Health Services Administration; ULOQ; coefficient of variation; dried urine spot; drug of abuse testing; enzyme multiplied immunoassay technique; gas chromatography–mass spectrometry; iMethod; liquid chromatography–tandem mass spectrometry; lower limit of quantification; quality control; upper limit of quantification