We present a method to calibrate Raman measurements of reactive systems without relying on thermodynamic models. Raman spectroscopy is able to detect multiple species even in reactive mixtures. Classical calibration methods require the knowledge of concentrations of all species as input. Typically, concentrations of intermediates cannot be prepared and fixed independently and are therefore calculated using thermodynamic models. The quality of the results thus depends on the accuracy of the thermodynamic model. In this paper, we present a method based only on stoichiometric balances and electroneutrality. By avoiding the use of thermodynamic models in the calibration step, the risk of overfitting spectroscopic data to a thermodynamic model is avoided. The presented method is demonstrated for the reactive system monoethanolamine, water, and CO2 and is validated by a thermodynamic model taken from the literature. While the model-free calibration is demonstrated for Raman spectroscopy in this work, the approach is generic should thus be applicable to most spectroscopic techniques. (C) 2015 Elsevier B.V. All rights reserved.