Patients with chronic kidney disease or renal insufficiency have increased risk of urothelial cancer. Increased excretion of tryptophan metabolites in the urine has been observed in renal-insufficient rats. Aberrant tryptophan metabolism may play a role in the development of urothelial cancer. To evaluate the relevance of tryptophan metabolism in urothelial cancer, we developed a LC-MS-MS method to simultaneously quantify five tryptophan metabolites as well as tryptophan in urine. Urine samples were cleaned up by on-line solid phase extraction before separation by C18-amide reversed-phase chromatography. The analytes were detected in positive ion multiple reaction monitoring (MRM) mode with a lower limit of quantification at 1 ng/ml. The relative standard deviation (RSD) for recovery and precision ranged between 3.10–7.65% and 1.80–9.33%, respectively. A preliminary study on 45 upper urinary tract cancer patients and 35 controls showed that cancer patients had higher levels of kynurenine and kynurenic acid in urine and elevated urinary kynurenine/tryptophan ratios. Although further studies are needed, our preliminary data suggest that tryptophan metabolites can be potential biomarkers for diagnosis and prognosis of urothelial cancer.
