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Ultra‐performance liquid chromatography/tandem mass spectrometric quantification of structurally diverse drug mixtures using an ESI‐APCI multimode ionization source
Author(s) -
Yu Kate,
Di Li,
Kerns Edward,
Li Susan Q.,
Alden Peter,
Plumb Robert S.
Publication year - 2007
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.2908
Subject(s) - chemistry , chromatography , atmospheric pressure chemical ionization , mass spectrometry , selected reaction monitoring , analytical chemistry (journal) , analyte , liquid chromatography–mass spectrometry , tandem mass spectrometry , high performance liquid chromatography , ionization , detection limit , direct electron ionization liquid chromatography–mass spectrometry interface , electrospray ionization , chemical ionization , ion , organic chemistry
Abstract We report in this paper an ultra‐performance liquid chromatography/tandem mass spectrometric (UPLC®/MS/MS) method utilizing an ESI‐APCI multimode ionization source to quantify structurally diverse analytes. Eight commercial drugs were used as test compounds. Each LC injection was completed in 1 min using a UPLC system coupled with MS/MS multiple reaction monitoring (MRM) detection. Results from three separate sets of experiments are reported. In the first set of experiments, the eight test compounds were analyzed as a single mixture. The mass spectrometer was switching rapidly among four ionization modes (ESI+, ESI−, APCI−, and APCI+) during an LC run. Approximately 8–10 data points were collected across each LC peak. This was insufficient for a quantitative analysis. In the second set of experiments, four compounds were analyzed as a single mixture. The mass spectrometer was switching rapidly among four ionization modes during an LC run. Approximately 15 data points were obtained for each LC peak. Quantification results were obtained with a limit of detection (LOD) as low as 0.01 ng/mL. For the third set of experiments, the eight test compounds were analyzed as a batch. During each LC injection, a single compound was analyzed. The mass spectrometer was detecting at a particular ionization mode during each LC injection. More than 20 data points were obtained for each LC peak. Quantification results were also obtained. This single‐compound analytical method was applied to a microsomal stability test. Compared with a typical HPLC method currently used for the microsomal stability test, the injection‐to‐injection cycle time was reduced to 1.5 min (UPLC method) from 3.5 min (HPLC method). The microsome stability results were comparable with those obtained by traditional HPLC/MS/MS. Copyright © 2007 John Wiley & Sons, Ltd.