While the titrimetric assay is one of the most precise analytical techniques available, only a limited list of complexometric chelators is available, as many otherwise promising reagents are not water-soluble. Recent work demonstrated successful titrimetry with ion-exchanging polymeric nanospheres containing hydrophobic complexing agents, socalled ionophores, opening an exciting avenue in this field. However, this method was limited to ionophores of very high affinity to the analyte and

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... d a relatively limited titration capacity. To overcome these two limitations, we report here on solvent based titration reagents. This heterogeneous titration principle is based on the dissolution of all hydrophobic recognition components in a solvent such as dichloromethane (CH 2 Cl 2 ) where the ionophores are shown to maintain a high affinity to the target ions. HSV (hue, saturation, value) analysis of the images captured with a digital camera provides a convenient and inexpensive way to determine the end point. This approach is combined with an automated titration setup. The titrations of the alkali metals K + , Na + , and Li + in aqueous solution are successfully demonstrated. The potassium concentration in human serum without pretreatment was precisely and accurately determined as 4.38 mM ± 0.10 mM (automated titration), which compares favorably with atomic emission spectroscopy (4.47 mM ± 0.20 mM).