ultra-fast analysis of plasma and intracellular levels of hiv protease inhibitors in children a clinical application of maldi mass spectrometry超高速分析等离子体和细胞内水平儿童hiv蛋白酶抑制剂的临床应用谱质谱分析.pdf

Ultra-Fast Analysis of Plasma and Intracellular Levels of HIV Protease Inhibitors in Children: A Clinical Application of MALDI Mass Spectrometry 1,2,3 3 1 1 Jeroen J. A. van Kampen , Mariska L. Reedijk , Peter C. Burgers , Lennard J. M. Dekker , Nico G. 2 4 5 3 6 Hartwig , Ineke E. van der Ende , Ronald de Groot , Albert D. M. E. Osterhaus , David M. Burger , 1 . 3. Theo M. Luider * , Rob A. Gruters 1 Department of Neurology, Erasmus MC, Rotterdam, The Netherlands, 2 Department of Paediatrics, Erasmus MC – Sophia, Rotterdam, The Netherlands, 3 Department of Virology, Erasmus MC, Rotterdam, The Netherlands, 4 Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands, 5 Department of Paediatrics, University Medical Centre Nijmegen, Nijmegen, The Netherlands, 6 Department of Clinical Pharmacy, University Medical Centre Nijmegen, Nijmegen, The Netherlands 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 det