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Title

Method development aspects for the quantitation of pharmaceutical compounds in human plasma with a matrix-assisted laser desorption/ionization source in the multiple reaction monitoring mode

Authors
Kovarik, Peter
Bourgogne, Emmanuel
Published in Rapid Communications in Mass Spectrometry. 2007, vol. 21, no. 6, p. 911-919
Abstract The present work investigates various method development aspects for the quantitative analysis of pharmaceutical compounds in human plasma using matrix-assisted laser desorption/ionization and multiple reaction monitoring (MALDI-MRM). Talinolol was selected as a model analyte. Liquid-liquid extraction (LLE) and protein precipitation were evaluated regarding sensitivity and throughput for the MALDI-MRM technique and its applicability without and with chromatographic separation. Compared to classical electrospray liquid chromatography/mass spectrometry (LC/ESI-MS) method development, with MALDI-MRM the tuning of the analyte in single MS mode is more challenging due to interfering matrix background ions. An approach is proposed using background subtraction. With LLE and using a 200 microL human plasma aliquot acceptable precision and accuracy could be obtained in the range of 1 to 1000 ng/mL without any LC separation. Approximately 3 s were required for one analysis. A full calibration curve and its quality control samples (20 samples) can be analyzed within 1 min. Combining LC with the MALDI analysis allowed improving the linearity down to 50 pg/mL, while reducing the throughput potential only by two-fold. Matrix effects are still a significant issue with MALDI but can be monitored in a similar way to that used for LC/ESI-MS analysis.
Keywords AlgorithmsBlood Chemical Analysis/instrumentation/methodsEquipment DesignEquipment Failure AnalysisHumansMicrochemistry/instrumentation/methodsPharmaceutical Preparations/bloodPropanolamines/bloodReproducibility of ResultsSensitivity and SpecificitySpectrometry, Mass, Electrospray Ionization/instrumentation/methodsSpectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/instrumentation/methods
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PMID: 17295425
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KOVARIK, Peter et al. Method development aspects for the quantitation of pharmaceutical compounds in human plasma with a matrix-assisted laser desorption/ionization source in the multiple reaction monitoring mode. In: Rapid Communications in Mass Spectrometry, 2007, vol. 21, n° 6, p. 911-919. doi: 10.1002/rcm.2912 https://archive-ouverte.unige.ch/unige:2399

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Deposited on : 2009-08-11

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