Normal and malignant melanocytes produce
melanins and
melanin-related metabolites, most of which are retained in the cells but some are secreted into the blood and then excreted in the urine. In this study, we developed a method to measure levels of
eumelanin in urine samples and evaluated its clinical significance in comparison with the
melanin-related metabolites
6-hydroxy-5-methoxyindole-2-carboxylic acid (
6H5MI2C) and
5-S-cysteinyldopa (5-S-CD), and with
pheomelanin, measured after degradation as
4-amino-3-hydroxyphenylalanine (4-AHP). The method is based on the production of
pyrrole-2,3,5-tricarboxylic acid (PTCA) on
permanganate oxidation of
eumelanin, followed by quantification by liquid chromatography. For 118 urine samples from 10 control subjects, mean urinary excretions of PTCA,
6H5MI2C, 5-S-CD and
4-AHP were 19, 67, 37 and 59 micromol/mol
creatinine respectively. In
melanoma patients (n = 45), the mean urinary excretions of PTCA,
6H5MI2C, 5-S-CD, and
4-AHP were 91, 926, 4070 and 3530 micromol/mol
creatinine respectively. Median level of PTCA in
melanoma patients was elevated 2.1-fold compared with control subjects. The degrees of elevation for
6H5MI2C, 5-S-CD, and
4-AHP were 1.8-, 22- and 6.2-fold respectively. Thus, although urinary PTCA is of little clinical value in following the progression of
melanoma, urinary
4-AHP appears to be of considerable value in this respect.