Investigation of Cytotoxic Activity of Mitoxantrone at the Individual Cell Level by Using Ionic-Liquid-Tag-Enhanced Mass Spectrometry.

A novel mitoxantrone conjugate was synthesized by coupling mitoxantrone with ionic liquid tags, and cytotoxic behavior of the designed conjugate was studied in normal and cancer cell lines. The synthesized mitoxantrone conjugate was oil at physiological temperatures and demonstrated high aqueous solubility. Sensitivity of electrospray ionization mass spectrometry (ESI-MS) to the mitoxantrone conjugate was improved by an order of magnitude, in comparison with original mitoxantrone dihydrochloride. The observed ESI-MS signals were shifted to a "clearer" lower-mass region of the spectrum, which allowed investigation of the drug at the level of individual cells. The ionic liquid tags proposed in the present work consist of an easily available imidazolium salt residue and show a number of key advantages from the points of view of drug conjugate synthesis, drug delivery and analytic detection.