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The variation of ionization efficiency for different compounds has puzzled researchers since the invention of the electrospray mass spectrometry (ESI/MS). Ionization depends on the properties of the compound, eluent, matrix, and instrument. Despite significant research, some aspects have remained unclear. For example, research groups have reached contradicting conclusions regarding the ionization processes. One of the best-known is the significance of the logP value for predicting the ionization efficiency. In this tutorial review, we ana