Correction: Ultra-Fast Analysis of Plasma and Intracellular Levels of HIV Protease Inhibitors in Children: A Clinical Application of MALDI Mass Spectrometry

Abstract

HIV protease inhibitors must penetrate into cells to exert their action. Differences in the intracellular pharmacokinetics of these drugs may explain why some patients fail on therapy or suffer from drug toxicity. Yet, there is no information available on the intracellular levels of HIV protease inhibitors in HIV infected children, which is in part due to the large amount of sample that is normally required to measure the intracellular concentrations of these drugs. Therefore, we developed an ultra-fast and sensitive assay to measure the intracellular concentrations of HIV protease inhibitors in small amounts of peripheral blood mononuclear cells (PBMCs), and determined the intracellular concentrations of lopinavir and ritonavir in HIV infected children. An assay based on matrix-assisted laser desorption/ionization (MALDI) -triple quadrupole mass spectrometry was developed to determine the concentrations of HIV protease inhibitors in 10 mL plasma and 1610 6 PBMCs. Precisions and accuracies were within the values set by the FDA for bioanalytical method validation. Lopinavir and ritonavir did not accumulate in PBMCs of HIV infected children. In addition, the intracellular concentrations of lopinavir and ritonavir correlated poorly to the plasma concentrations of these drugs. MALDI-triple quadrupole mass spectrometry is a new tool for ultra-fast and sensitive determination of drug concentrations which can be used, for example, to assess the intracellular pharmacokinetics of HIV protease inhibitors in HIV infected children.

Analytical Performance Evaluation of New DESI Enhancements for Targeted Drug Quantification in Tissue Sections

“…Moreover, DI-MS methods offer a considerable advantage of rapidity and low-sample input for drug quantification. DI-MS methods have extensively been used for the quantification of drugs in fluids [5][6][7][8][9][10][11], recently supported by full method validation [11]. In addition to the advantage of rapidity, DI-MS of drugs in tissue sections preserves histological contexts and can be performed at different dimensional scales, from profiling (when regions of interest are measured) [1,2,12] to imaging (when a complete drug mapping is necessary) .…”

Important Requirements for the Selection of Internal Standards during the Development of Desorption/Ionization Assays for Drug Quantification in Biological Matrices—A Practical Example

“…Desorption/ionization (DI) methods offer a range of outstanding advantages for drug quantification in biological matrices [ 1 , 2 ], using assays which can be validated according to regulatory guidelines [ 1 ]. These advantages include the rapidity of sample preparation and analysis from any biological matrix, including fluids [ 3 , 4 , 5 , 6 , 7 , 8 ], and the ability to quantify drugs in their histological context when tissue sections are used [ 1 , 9 , 10 ]. Our group has previously shown that the surface properties of the biological matrix in desorption electrospray ionization (DESI) [ 11 ] or the matrix crystallization effects in matrix-assisted laser desorption/ionization (MALDI) [ 2 , 12 ] can strongly affect signal stability compared to electrospray ionization (ESI).…”