Motivation: Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI) facilitates the analysis of large organic molecules. However, the complexity of biological samples and MALDI data acquisition leads to high levels of variation, making reliable quantification of samples difficult. We present a new analysis approach that we believe is well-suited to the properties of MALDI mass spectra, based upon an Independent Component Analysis derived for Poisson sampled data. Simple analyses have been limited to studying small numbers of mass peaks, via peak ratios, which is known to be inefficient. Conventional PCA and ICA methods have also been applied, which extract correlations between any number of peaks, but we argue makes inappropriate assumptions regarding data noise, i.e. uniform and Gaussian.Results: We provide evidence that the Gaussian assumption is incorrect, motivating the need for our Poisson approach. Themethod is demonstrated bymaking proportionmeasurements fromlipid-rich binary mixtures of lamb brain and liver, and also goat and cow milk. These allow our measurements and error predictions to be compared to ground truth.