Noninvasive sampling of phenylalanine by reverse iontophoresis.

While iontophoresis is typically associated with drug delivery across the skin, the symmetry of the technique permits its application to the essentially noninvasive withdrawal of biologically important analytes from the subcutaneous space to the body's surface. The identification of other substances which can be monitored by this procedure, and to its optimization and development as a more general clinical chemistry tool, is a long-term objective. In this paper, we describe a preliminary in vitro investigation into the feasibility of extracting and analyzing the amino acid, phenylalanine, with the ultimate aim to develop a diagnostic test for phenylketonuria, a potentially fatal metabolic disease in infants. Over a subdermal concentration range of 1-10 mM phenylalanine, reverse iontophoretic extraction was rapid, easily detectable and highly linear. Manipulation of the electrolyte composition surrounding the cathode (i.e., the site of collection of the iontophoretically-extracted material) enabled phenylalanine to be electrotransported at a rate of approximately 6 nmol/cm(2)/h when present subdermally at 1 mM. The potential exists, therefore, to use this approach for the noninvasive detection of systemic amino acid levels in vivo. However, such a development will necessitate a suitable and convenient analytical approach (e.g., a biosensor), with a sensitivity about 10-times greater than that used in this work, which can be combined successfully with the reverse iontophoretic extraction technology.