The use of multiple fragmentation events in a single laser shot for improved drug quantification by MALDI TOF/TOF Mass spectrometry

Abstract

Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry is an important molecular detection technology due to its extensive mass range, sensitivity, rapid analysis time, and minimal sample preparation. However, quantitative MALDI-TOF approaches have historically suffered from poor accuracy and precision, mainly due to the variability in analyte distribution and a non-uniform sample surface and analyte suppression [1-5]. In order to alleviate spectral complexity at low m/z and ensure chemical specificity, tandem mass spectrometry (MS/MS) is often employed. Herein, we demonstrate that multiple MS/MS events can be performed in a single laser shot [8,9]. This allows the reference of analyte instensity to that of an internal standard in each laser shot, thereby improving accuracy, precision, and throughput.