Ultra-fast analysis of plasma and intracellular levels of HIV protease inhibitors in children: a clinical application of MALDI mass spectrometry.

PloS One
Jeroen J A van KampenRob A Gruters

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 microL plasma and 1x10(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 p...Continue Reading

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Citations

Nov 6, 2012·Clinica Chimica Acta; International Journal of Clinical Chemistry·Eddy Wing Yin NgTerence Chuen Wai Poon
Apr 9, 2014·Journal of the American Society for Mass Spectrometry·Martin PabstRenato Zenobi
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Aug 16, 2016·Bioanalysis·Andrea E SteuerThomas Kraemer
Feb 20, 2010·Mass Spectrometry Reviews·Jeroen J A van KampenTheo M Luider

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MDS
density gradient centrifugation

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