Determination of antituberculosis drug concentration in human plasma by MALDI-TOF/TOF

Stefania Notari, Carmine Mancone, Manuel Sergi, Francesca Gullotta, Nazzario Bevilacqua, Massimo Tempestilli, Rocco Urso, Francesco Nicola Lauria, Leopoldo Paolo Pucillo, Marco Tripodi, Paolo Ascenzi

Research output: Contribution to journalArticlepeer-review


Therapeutic drug monitoring allows to determine the best dosage regimen adapted to each patient optimizing the therapeutic benefits, while minimizing the risk for side effects. Here, the first methodological approach based on matrix-assisted laser desorption/ionization source equipped with tandem time-of-flight (MALDI-TOF/TOF) mass spectrometry for the determination of the antituberculosis (anti-TB) drugs ethambutol, pyrazinamide, rifampicin, and streptomycin concentration in the plasma of tuberculosis-infected patients is reported. The volume of the plasma sample was 200 lL. Plasma samples were cleaned-up by protein precipitation and evaporated in a water bath under a nitrogen stream. The extracted samples were reconstituted with 200 lL of 50% methanol-0.03% formic acid solution (v/v), spiked with known amounts of anti-TB drugs, mixed (1:1) with a saturated matrix solution (4-hydroxybenzoic acid in 50% acetonitrile-0.1% trifluoracetic acid solution; v/v), and spotted onto the MALDI-TOF/TOF sample target plate. The anti-TB drug concentration was determined by standard additions analysis. Regression of standard additions was linear over the whole anti-TB drug concentration range explored (the final anti-TB drug concentration ranged from 0.20 to 200 pmol/μL). The absolute recovery of the anti-TB drugs ranged between 87 and 110%. The minimal ethambu-tol, pyrazinamide, rifampicin, and streptomycin concentration detectable by MALDI-TOF/TOF is 0.08, 0.20, 0.12, and 0.15 pmol/μL, respectively.

Original languageEnglish
Pages (from-to)387-393
Number of pages7
JournalIUBMB Life
Issue number5
Publication statusPublished - May 2010


  • Antituberculosis drug determination
  • Human plasma

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Clinical Biochemistry
  • Molecular Biology
  • Genetics


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