Mixed-mode solid-phase extraction procedures for the determination of MDMA and metabolites in urine using LGMS, LC-UV, or GC-NPD

A solid-phase extraction (SPE) procedure was developed for the liquid chromatographic-mass spectrometric (LC-MS) analysis of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolites 3,4-methylenedioxyamphetamine (MDA) and N,α -dimethyl-(3-methoxy-4-hydroxybenzene) (HMMA) ethanamine in urine. The procedure, with modifications, was also demonstrated using LC-UV and GC-nitrogen-phosphorus detection (NPD). A mixed-mode cation exchange SPE cartridge was effective for both reducing matrix impurities and for preconcentrating the analytes for the analysis. The concentration range investigated spanned from 0.10 to 20 μg/mL with recoveries ranging from 88% to 108% for all analytes using LC-MS. Both LC methods and the GC method allow for complete resolution of MDMA, MDA, and HMMA, as well as the internal standards (MDMA-d5 and 3,4-methylenedioxypropylamphetamine) in less than 10 min. Lower limits of quantitation (LLOQ) for the LC-MS method were 0.1 pg/mL for MDMA and MDA and 0.04 μg/mL for HMMA. Compared with LC-UV and GC-NPD, the LC-MS method requires the least amount of sample manipulation and provided the highest sample throughput. GC-NPD gave comparable selectivity, but the extra sample manipulation steps required contributed to lower recovery, lower precision, and increased time for the analysis. LC-MS analysis demonstrated better selectivity for the determination of HMMA in incurred samples compared with LC-UV analysis.