Development and validation of an LC-MS/MS method for the quantification of mescaline and major metabolites in human plasma
Journal of Pharmaceutical and Biomedical Analysis – August 01, 2022
Source: OpenAlex
Summary
Mescaline, a psychedelic compound, can now be accurately quantified in human plasma using an innovative bioanalytical method. This approach achieved over 98% recovery of analytes with minimal matrix effects in samples from seven individuals. The method demonstrated intra-assay accuracy ranging from 84.9% to 106% and precision under 7.33%. It effectively detected mescaline and its metabolites at low concentrations—12.5 ng/mL for mescaline and TMPAA, and 1.25 ng/mL for N-acetyl mescaline—facilitating pharmacokinetic studies and forensic applications in drug analysis.
Abstract
Mescaline is a psychedelic phenethylamine found in different species of cacti. Currently, mescaline's acute subjective effects and pharmacokinetics are investigated in several modern clinical studies. Therefore, we developed a bioanalytical method for the rapid quantification of mescaline and its metabolites in human plasma. Mescaline and its metabolites 3,4,5-trimethoxyphenylacetic acid (TMPAA), N-acetyl mescaline (NAM), and 3,5-dimethoxy-4-hydroxyphenethylamine (4-desmethyl mescaline) were simultaneously analyzed by ultra-high performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Optimal chromatographic separation was achieved with an Acquity Premier HSS T3 C18 column. The analytes were detected in positive ionization mode using scheduled multiple reaction monitoring. A single step extraction method was implemented to enable fast and automatable plasma sample preparation. An intra-assay accuracy between 84.9% and 106% and a precision of ≤ 7.33% was observed in three validation runs. Plasma was extracted by simple protein precipitation, resulting in a complete recovery (≥ 98.3%) and minor matrix effects (≤ 7.58%). No interference with endogenous matrix components could be detected in human plasma samples (n = 7). Importantly, method sensitivity sufficed for assessing pharmacokinetic parameters of mescaline in clinical study samples with lower limits of quantification of 12.5, 12.5, and 1.25 ng/mL for mescaline, TMPAA, and NAM, respectively. Nonetheless, 4-desmethyl mescaline could not be selectively quantified in pharmacokinetic samples due to interference with another mescaline metabolite. Overall, we developed and validated a reliable and very easy-to-use method for forensic applications as well as investigating the clinical pharmacokinetics of mescaline.