Cationic drug analysis using matrix-assisted laser desorption/ionization mass spectrometry: application to influx kinetics, multidrug resistance, and intracellular chemical change
| Autor: | Gary Siuzdak, Darryl Rideout, Andres Bustamante |
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| Rok vydání: | 1993 |
| Předmět: |
Tris
Stereochemistry Kinetics Drug Resistance Breast Neoplasms Adenocarcinoma Mass spectrometry Mass Spectrometry Cell Line chemistry.chemical_compound Structure-Activity Relationship Onium Compounds Organophosphorus Compounds Cations Tumor Cells Cultured Humans Chemical ionization Multidisciplinary Chromatography Hypopharyngeal Neoplasms Molecular Structure Chemistry Lasers Cationic polymerization Onium compound Biological Transport Trityl Compounds Matrix-assisted laser desorption/ionization Doxorubicin Benzaldehydes Carcinoma Squamous Cell Female Quantitative analysis (chemistry) Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 90(21) |
| ISSN: | 0027-8424 |
| Popis: | Highly sensitive and convenient analysis of intracellular cationic drugs has been achieved by applying matrix-assisted laser desorption/ionization mass spectrometry (MALD-MS). Tetraphenylphosphonium cation was readily identified and quantified (using methyltriphenylphosphonium cation as an internal standard) at subpicomole levels in crude lysate from < 4 x 10(3) FaDu human hypopharyngeal carcinoma cells. A quantitative MALD-MS time course for tetraphenylphosphonium cation accumulation into FaDu cells was comparable to a time course using scintillation counting with tritiated tetraphenylphosphonium. MALD-MS was also capable of demonstrating the reduced accumulation of the cationic drug rhodamine-123 by DoxR MCF7, a multiply drug-resistant human breast adenocarcinoma cell line, relative to the nonresistant parent line MCF7. In addition, MALD-MS was used to follow a chemical reaction inside intact FaDu cells: the formation of a hydrazone (II-51) from benzaldehyde and an acylhydrazide, 5-[tris(4-dimethylaminophenyl)phosphonio]pentanoyl hydrazide (II-25). These results suggest that MALD-MS may provide a rapid and practical alternative to existing methods for the analysis of cationic drugs, toxins, and their metabolites in cells and tissues. |
| Databáze: | OpenAIRE |
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