title: Evaluation of a straightforward and rapid method for the therapeutic drug monitoring of digitoxin by LC-MS/MS.
abstract: OBJECTIVE
  Therapeutic drug monitoring of digitoxin is strongly recommended but metabolites of digitoxin and digitoxin-like immunoreactive substances may interfere with widely used immunoassays. Recently evaluated assays on LC-MS/MS have the drawback of long turnaround time. We sought to evaluate a specific method on LC-MS/MS optimizing sample preparation thereby significantly reducing turnaround time.
  
  
  METHODS
  Linearity, functional sensitivity, and precision of the method were established. External quality control samples were used for the evaluation of accuracy of the LS-MS/MS method. In addition, digitoxin concentrations in 221 samples were measured by LC-MS/MS and immunoassay.
  
  
  RESULTS
  Linearity was validated between 0.15 and 80 ng/mL. Limit of quantification was established at 0.14 ng/mL. Between-day imprecision lay between 1.4 and 4.9% and meets the conditions required for routine analysis. Comparison to results obtained by immunoassay revealed a mean difference of -1.2 ng/mL.
  
  
  CONCLUSIONS
  By optimizing preparation steps turnaround time was shorter for LC-MS/MS than for immunoassay. This did not result in increased susceptibility to matrix effects. Analytical performance was sufficient for routine analysis. Therefore, the method is suitable for routine therapeutic drug monitoring of digitoxin.
authors: Institut fuer Klinische Chemie und Labordiagnostik, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
authors: Sibylle
authors: S
authors: Bremer-Streck
authors: Michael
authors: M
authors: Kiehntopf
authors: Stefan
authors: S
authors: Ihle
authors: Klas
authors: K
authors: Boeer
mesh_terms: D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004074:Digitoxin / Q000097:blood*; D016903:Drug Monitoring / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D007118:Immunoassay; D013058:Mass Spectrometry / Q000379:methods*; D015203:Reproducibility of Results
chemical_list: D004074:Digitoxin
keywords: Digitoxin; Interference; LC-MS/MS