Determination of the antiretroviral drug tenofovir in plasma from HIV-infected adults by ultrafast isotope dilution MALDI-triple quadrupole tandem mass spectrometry

Roland Meesters, Jeroen van Kampen, Rachel Scheuer, Marchina Ende, Rob Gruters, Theo Luider

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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 mu mol/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 mu mol/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 mu mol/l and measured plasma TNV concentrations were within the therapeutically relevant concentration range. Copyright (C) 2011 John Wiley & Sons, Ltd.
Original languageUndefined/Unknown
Pages (from-to)282-289
Number of pages8
JournalJournal of Mass Spectrometry
Issue number3
Publication statusPublished - 2011

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