1. Determination of the antiretroviral drug tenofovir in plasma from HIV-infected adults by ultrafast isotope dilution MALDI-triple quadrupole tandem mass spectrometry.
- Author
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Meesters RJ, van Kampen JJ, Scheuer RD, van der Ende ME, Gruters RA, and Luider TM
- 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
- 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., (Copyright © 2011 John Wiley & Sons, Ltd.)
- Published
- 2011
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