Abstract
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 language | English |
|---|---|
| Pages (from-to) | 387-393 |
| Number of pages | 7 |
| Journal | IUBMB Life |
| Volume | 62 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2010 |
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Keywords
- Antituberculosis drug determination
- Human plasma
- MALDI-TOF/TOF
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Clinical Biochemistry
- Molecular Biology
- Genetics
Cite this
Determination of antituberculosis drug concentration in human plasma by MALDI-TOF/TOF. / Notari, Stefania; Mancone, Carmine; Sergi, Manuel; Gullotta, Francesca; Bevilacqua, Nazzario; Tempestilli, Massimo; Urso, Rocco; Lauria, Francesco Nicola; Pucillo, Leopoldo Paolo; Tripodi, Marco; Ascenzi, Paolo.
In: IUBMB Life, Vol. 62, No. 5, 05.2010, p. 387-393.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Determination of antituberculosis drug concentration in human plasma by MALDI-TOF/TOF
AU - Notari, Stefania
AU - Mancone, Carmine
AU - Sergi, Manuel
AU - Gullotta, Francesca
AU - Bevilacqua, Nazzario
AU - Tempestilli, Massimo
AU - Urso, Rocco
AU - Lauria, Francesco Nicola
AU - Pucillo, Leopoldo Paolo
AU - Tripodi, Marco
AU - Ascenzi, Paolo
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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.
KW - Antituberculosis drug determination
KW - Human plasma
KW - MALDI-TOF/TOF
UR - http://www.scopus.com/inward/record.url?scp=77953581278&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953581278&partnerID=8YFLogxK
U2 - 10.1002/iub.321
DO - 10.1002/iub.321
M3 - Article
VL - 62
SP - 387
EP - 393
JO - IUBMB Life
JF - IUBMB Life
SN - 1521-6543
IS - 5
ER -