Premium
Determination of the antiretroviral drug tenofovir in plasma from HIV‐infected adults by ultrafast isotope dilution MALDI‐triple quadrupole tandem mass spectrometry
Author(s) -
Meesters Roland J. W.,
van Kampen Jeroen J. A.,
Scheuer Rachel D.,
van der Ende Marchina E.,
Gruters Rob A.,
Luider Theo M.
Publication year - 2011
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.1897
Subject(s) - chemistry , triple quadrupole mass spectrometer , chromatography , mass spectrometry , detection limit , isotope dilution , selected reaction monitoring , tandem mass spectrometry , tenofovir , human immunodeficiency virus (hiv) , virology , biology
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.