All of the following are ions with a positive charge and may be introduced into tissue with the positive pole of a direct current EXCEPT

• A. Copper
• B. Zinc
• C. Histamine
• D. Salicylic acid

Answer: (D)

In iontophoresis, the direct current drives charged molecules through the skin by electromotive force, so only ions carrying a positive charge can be repelled from the positive electrode into the tissue. Metal ions like copper and zinc form positive cations (Cu2+, Zn2+) and a positively charged amine such as histamine will also carry a positive charge at physiological pH, making them suitable for delivery from the positive pole. Salicylic acid, however, is a weak acid with a pKa around 2.97; in typical topical or physiological conditions it exists largely as the negatively charged salicylate anion, not as a positive ion, so it cannot be driven into tissue from the positive pole. Therefore, salicylic acid is the one that cannot be delivered using the positive electrode.