Capillary column gas-liquid chromatography selected ion monitoring assay for [13C, 15N]N-methyltryptamine in human urine: failure to detect conversion of [13C,15N]tryptamine in schizophrenia patients.

A capillary column gas-liquid chromatography selected ion monitoring-based method was developed for the measurement of [13C,15N]N-methyltryptamine ( NMT ) in human urine. The method was employed to establish the extent of conversion of [13C,15N]tryptamine to the correspondingly labeled NMT in schizophrenic patients in an attempt to demonstrate whether methylation of tryptamine plays a role in schizophrenia. Mass spectrometric detection in the assay procedure is via chemical ionization (Isobutane) with monitoring of the MH+ ions of the trimethylsilyl derivatives of [13C,15N] NMT and the internal standard, [2H3,13C,15N] NMT . The assay possesses a sensitivity limit (using 200 ml of urine) of ca. 0.1 ng/ml, corresponding to substrate conversion of ca. 0.00005% with a 75 mg dose (i.v.) of labeled tryptamine. Evidence for methylation was found with only one of seven patients studied; the extent of substrate conversion for the one individual was only 0.0001%. These results do not support the indoleamine--methylation hypothesis of schizophrenia.