title: Measurement of teicoplanin by liquid chromatography-tandem mass spectrometry: development of a novel method.
abstract: BACKGROUND
  Teicoplanin is an antibiotic used for the treatment of endocarditis, osteomyelitis, septic arthritis and methicillin-resistant Staphylococcus aureus. Teicoplanin is emerging as a suitable alternative antibiotic to vancomycin, where their trough serum levels are monitored by immunoassay routinely. This is the first report detailing the development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring teicoplanin in patients' serum.
  
  
  METHODS
  An Acquity™ UPLC (ultra-pressure liquid chromatography) tandem mass spectrometer was used to measure teicoplanin concentrations in samples from patients, quality assurance schemes and quality control preparations. Ristocetin was successfully implemented as a suitable internal standard. Ion suppression, linearity, stability, matrix effects, recovery, imprecision, lower limits of quantification and detection, interference and method comparison against immunoassay were all assessed.
  
  
  RESULTS
  Teicoplanin and ristocetin had elution times of 1.39 and 1.24 min, respectively. Ion suppression was shown to be negligible, and linear calibration curves (0-200 μg/mL) were consistently reproduced to have r(2) values >0.99. Postextraction stability was achieved up to 20 h, while matrix effects were minimal coupled with sample recovery of >93%. The lower limit of quantification was 1 μg/mL, and 0.2 μg/mL was the lower limit of detection. Interference with other antibiotics was dependent on the combination of drugs present in patients' serum. A method comparison between immunoassay and LC-MS/MS suggested a negative bias for tandem mass spectrometry.
  
  
  CONCLUSIONS
  This novel method of teicoplanin determination by LC-MS/MS is proven to be a robust protocol that is consistent and reproducible. Clinicians searching for alternatives in therapeutic drug monitoring may have an additional option that is potentially more accurate and specific.
authors.affiliation: Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool and Broadgreen University Hospital, 4th floor Duncan Building, Liverpool L7 8XP, UK. Francis.Fung@nhs.net
authors.forename: Francis H Y
authors.initials: FH
authors.lastname: Fung
authors.forename: Jonathan C Y
authors.initials: JC
authors.lastname: Tang
authors.forename: John P P
authors.initials: JP
authors.lastname: Hopkins
authors.forename: John J
authors.initials: JJ
authors.lastname: Dutton
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Bailey
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Davison
mesh_terms: D000900:Anti-Bacterial Agents / Q000097:blood*; D001774:Blood Chemical Analysis / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D057230:Limit of Detection; D053719:Tandem Mass Spectrometry; D017334:Teicoplanin / Q000097:blood*
chemical_list: D000900:Anti-Bacterial Agents; D017334:Teicoplanin