Development and clinical application of an LC-MS-MS method for mescaline in urine

Mescaline (3,4,5-trimethoxyphenylethylamine) is an hallucinogenic psychoactive substance present in several species of cacti. Mescaline has a documented use dating back 5700 years. In more recent years, the interest in hallucinogenic designer drugs such as ecstasy has also triggered interest in the naturally occurring mescaline. This study was undertaken to develop a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for the screening and confirmation of mescaline in human urine samples and to apply this method to routine testing in patient samples. For the screening procedure, chromatographic separation was achieved on a 5-μm HyPURITY C18 column, using a methanol gradient in ammonium acetate buffer. The MS-MS analysis was performed using selected reaction monitoring; the transitions monitored were m/z 212.3 → m/z 180.3 for mescaline and m/z 221.3 → m/z 186.3 for the deuterated internal standard (mescaline-d9). The detection limit for mescaline in urine matrix was 3-5 μg/L, the upper limit of quantification was 10,000 μg/L, and the total coefficient of variation for spiked samples containing 10 to 1025 μg/L was < 8.5%. The confirmation procedure included a sample clean-up by solid-phase extraction on a C18 cartridge, and one extra transition for mescaline (m/z 212.3 → m/z 195.2) was monitored. The LC-MS-MS method was found to be sensitive and specific for the routine detection of mescaline in urine. Among 462 urine samples collected from young people with alcohol or drug problems, 32% were positive for illicit drugs, but none for mescaline.