Rapid in vitro screening of drug-metal ion interactions

ABSTRACT The toxic side effects of synthetic drugs may, in part, be arising due to their interactions with essential metal ions, especially when the metal ions are administered along with the drug as mineral supplements. In this paper we report the feasibility of establishing such drug-metal ion interactions through in vitro spectrophotometric studies, which are rapid and can be used for routine screening prior to clinical studies. The interaction of the drugs levothyroxine and ranitidine with eight metal ions, copper(II), chromium(III), molybdenum(VI), magnesium(II), calcium(II), iron(II), manganese(II), and zinc(II), commonly used in mineral supplements, was verified through in vitro UV-visible spectrophotometric studies. The experiments were carried out at the physiological pH values 1.5, 7.4, and 8.0 and the concentrations of the drugs and mineral supplements used were comparable to those in their usual doses. These studies indicated interaction between ranitidine and calcium(II), magnesium(II), and iron(II) ions and between levothyroxine and copper(II) and iron(II) ions. A comparison of the results with those reported from clinical studies demonstrated the efficacy of this method.