Ultrafast and high-throughput mass spectrometric assay for therapeutic drug monitoring of antiretroviral drugs in pediatric HIV-1 infection applying dried blood spots
Open Access
- 15 July 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Analytical and Bioanalytical Chemistry
- Vol. 398 (1), 319-328
- https://doi.org/10.1007/s00216-010-3952-9
Abstract
Kaletra® (Abott Laboratories) is a co-formulated medication used in the treatment of HIV-1-infected children, and it contains the two antiretroviral protease inhibitor drugs lopinavir and ritonavir. We validated two new ultrafast and high-throughput mass spectrometric assays to be used for therapeutic drug monitoring of lopinavir and ritonavir concentrations in whole blood and in plasma from HIV-1-infected children. Whole blood was blotted onto dried blood spot (DBS) collecting cards, and plasma was collected simultaneously. DBS collecting cards were extracted by an acetonitrile/water mixture while plasma samples were deproteinized with acetone. Drug concentrations were determined by matrix-assisted laser desorption/ionization-triple quadrupole tandem mass spectrometry (MALDI-QqQ-MS/MS). The application of DBS made it possible to measure lopinavir and ritonavir in whole blood in therapeutically relevant concentrations. The MALDI-QqQ-MS/MS plasma assay was successfully cross-validated with a commonly used high-performance liquid chromatography (HPLC)–ultraviolet (UV) assay for the therapeutic drug monitoring (TDM) of HIV-1-infected patients, and it showed comparable performance characteristics. Observed DBS concentrations showed as well, a good correlation between plasma concentrations obtained by MALDI-QqQ-MS/MS and those obtained by the HPLC-UV assay. Application of DBS for TDM proved to be a good alternative to the normally used plasma screening. Moreover, collection of DBS requires small amounts of whole blood which can be easily performed especially in (very) young children where collection of large whole blood amounts is often not possible. DBS is perfectly suited for TDM of HIV-1-infected children; but nevertheless, DBS can also easily be applied for TDM of patients in areas with limited or no laboratory facilities.Keywords
This publication has 29 references indexed in Scilit:
- Biomedical application of MALDI mass spectrometry for small‐molecule analysisMass Spectrometry Reviews, 2010
- A novel LC–ESI-MS method for the simultaneous determination of etravirine, darunavir and ritonavir in human blood plasmaTalanta, 2009
- Development of an Inhibitor Screening Platform via Mass SpectrometrySLAS Discovery, 2008
- Ultra-fast quantitation of saquinavir in human plasma by matrix-assisted laser desorption/ionization and selected reaction monitoring mode detectionJournal of Chromatography B, 2008
- Simultaneous determination of 17 antiretroviral drugs in human plasma for quantitative analysis with liquid chromatography–tandem mass spectrometryBiomedical Chromatography, 2007
- Quantification of antiretroviral drugs in dried blood spot samples by means of liquid chromatography/tandem mass spectrometryRapid Communications in Mass Spectrometry, 2005
- Some fundamental and technical aspects of the quantitative analysis of pharmaceutical drugs by matrix‐assisted laser desorption/ionization mass spectrometryRapid Communications in Mass Spectrometry, 2005
- Automated solid-phase extraction method for the determination of piperaquine in capillary blood applied onto sampling paper by liquid chromatographyJournal of Chromatography B, 2004
- Use of Tandem Mass Spectrometry for Multianalyte Screening of Dried Blood Specimens from NewbornsClinical Chemistry, 2003
- HIV-1 Protease Inhibitors Are Substrates for theMDR1 Multidrug TransporterBiochemistry, 1998