Metabolic hydroxylation of 1-methyl-1,2,3,4-tetrahydro-beta-carboline in humans.

We characterized the metabolites of 1-methyl-1,2,3,4-tetrahydro-beta-carboline (MTBC) in human urine by gas chromatography-negative ion chemical ionization mass spectrometry (GC-NICIMS) and developed an analytical method using GC-NICIMS for their quantitative determination. When tetradeuterated MTBC was orally administered to a human subject, two peaks of the deuterated metabolites appeared on mass fragmentograms of the urine samples after administration. They were identified as tetradeuterated 6-hydroxy-MTBC (6-OH-MTBC) and 7-hydroxy-MTBC (7-OH-MTBC), indicating that MTBC was metabolically hydroxylated in humans. The proposed GC-NICIMS method could sensitively and selectively determine urinary 6-OH-MTBC and 7-OH-MTBC without interference from their artifactual formation during analysis. Its application to urine analysis has revealed that MTBC is excreted in human urine predominantly as the two hydroxylated metabolites, in which 6-OH-MTBC is present in both free and conjugated forms, whereas the 7-OH-MTBC of a conjugated form is much more than the 7-OH-MTBC of a free form.