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Qualitative and quantitative analysis of pharmaceutical compounds by MALDI-TOF mass spectrometry.
- Source :
-
Analytical chemistry [Anal Chem] 2006 Aug 01; Vol. 78 (15), pp. 5403-11. - Publication Year :
- 2006
-
Abstract
- In this report, we discuss key issues for the successful application of MALDI-TOF mass spectrometry to quantify drugs. These include choice and preparation of matrix, nature of cationization agent, automation, and data analysis procedures. The high molecular weight matrix meso-tetrakis(pentafluorophenyl)porphyrin eliminates chemical noise in the low-mass range, a "brushing" spotting technique in combination with prestructured target plates enables fast preparation of homogeneous matrix crystals, and addition of Li+ leads to intense cationized drug species. Complex biological samples were cleaned up using a 96-well solid-phase extraction plate, and the purified samples were automatically spotted by a pipetting robot. To obtain a suitable data analysis procedure for the quantitative analysis of drugs by MALDI-TOF mass spectrometry, various data processing parameters were evaluated on our two model drugs lopinavir and ritonavir. Finally, and most importantly, it is shown that the above-described procedure can be successfully applied to quantify clinically relevant concentrations of lopinavir, an HIV protease inhibitor, in extracts of small numbers of peripheral blood mononuclear cells (1 x 10(6)).
- Subjects :
- Adult
HIV Protease Inhibitors pharmacokinetics
Humans
Leukocytes, Mononuclear chemistry
Leukocytes, Mononuclear metabolism
Lopinavir
Pyrimidinones analysis
Pyrimidinones pharmacokinetics
Reproducibility of Results
Ritonavir analysis
Ritonavir pharmacokinetics
Sensitivity and Specificity
HIV Protease Inhibitors analysis
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods
Subjects
Details
- Language :
- English
- ISSN :
- 0003-2700
- Volume :
- 78
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Analytical chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 16878875
- Full Text :
- https://doi.org/10.1021/ac060436i