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Determination of the antiretroviral drug tenofovir in plasma from HIV-infected adults by ultrafast isotope dilution MALDI-triple quadrupole tandem mass spectrometry.
- Source :
-
Journal of mass spectrometry : JMS [J Mass Spectrom] 2011 Mar; Vol. 46 (3), pp. 282-9. - Publication Year :
- 2011
-
Abstract
- A new and reliable mass spectrometric method using an isotope dilution method in combination with matrix-assisted laser desorption/ionization-triple quadrupole tandem mass spectrometry (ID-MALDI-QqQ-MS/MS) has been developed and validated for the determination of concentrations of the antiretroviral drug tenofovir (TNV) in plasma from HIV-infected adults. The advantage of this new method is that (1) the method is ultrafast and (2) can be applied for high-throughput measurement of TNV in plasma. The method is based on a simple plasma deproteinization step in combination with the use of [adenine-(13) C(5) ]-TNV as the internal standard. TNV and [adenine-(13) C(5) ]-TNV were monitored by multiple reaction monitoring using the transition m/z 288.0 → 176.2 and m/z 293.2 → 181.2 for TNV and [adenine-(13) C(5) ]-TNV, respectively. The method was validated according to the most recent FDA guidelines for the development and validation of (new) bio-analytical assays. Validated method parameters were: linearity, accuracy, precision and stability of the method. The lowest limit of quantification was 0.10 µmol/l, whereas the limit of detection determined at a signal-to-noise ratio (S/N = 3:1) in pooled drug free human control plasma was 0.04 µmol/l. The validated method was successfully applied and tested for its clinical feasibility by the analysis of plasma samples from selected HIV-infected adults receiving the prodrug tenofovir disoproxil fumarate. Observed plasma TNV concentrations ranged between 0.11 and 0.76 µmol/l and measured plasma TNV concentrations were within the therapeutically relevant concentration range.<br /> (Copyright © 2011 John Wiley & Sons, Ltd.)
- Subjects :
- Adenine administration & dosage
Adenine blood
Adenine chemistry
Adult
Anti-HIV Agents chemistry
Humans
Isotope Labeling methods
Linear Models
Organophosphonates administration & dosage
Organophosphonates chemistry
Reproducibility of Results
Sensitivity and Specificity
Tandem Mass Spectrometry methods
Tenofovir
Triglycerides blood
Adenine analogs & derivatives
Anti-HIV Agents blood
HIV Infections blood
HIV Infections drug therapy
Organophosphonates blood
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods
Subjects
Details
- Language :
- English
- ISSN :
- 1096-9888
- Volume :
- 46
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of mass spectrometry : JMS
- Publication Type :
- Academic Journal
- Accession number :
- 21394844
- Full Text :
- https://doi.org/10.1002/jms.1897