Metabolites of ephedrines in human urine after administration of a single therapeutic dose

Abstract

Ephedrine (EPH), pseudoephedrine (PEPH), phenylpropanolamine (PPA), methylephedrine (MEPH) and cathine are sympathomimetic amines. These drugs are commonly found in over-the-counter (OTC) cold medicines and some dietary supplements. In Taiwan, the misuse of these drugs has resulted in an increase in athletic violations. Excretion studies of the ephedrine-related drugs have been performed to better understand the metabolic yields of ephedrines in urine. After consuming a single clinical dose of each of these drugs, urine samples from volunteers (n=3 for each drug) were subjected to tert-butyl-methyl-ether (TBME) extraction and trifluoroacetic acid (TFAA) derivatization before gas chromatography-mass spectrometry (GC-MS) analysis. Most ephedrines were excreted unchanged in urine, including EPH (40.9%), PEPH (72.2%), and PPA (59.3%). However, only a relatively small amount of MEPH (15.5%) was excreted unchanged in urine. In addition, a trace amount of PPA (1.6%) and cathine (0.7%) was found to be the metabolites of EPH and PEPH, respectively. Urinary EPH, PEPH, and PPA reached peaks at 2-6h and disappeared in urine at approximately 24-48 h post-administration. For MEPH, the peaks of excretion extended from 4 to 12h post-administration and were undetectable at approximately 48 h. A single clinical dose of EPH (25 mg) may exceed threshold level (10 microg/mL) in sport drug testing if the urine samples are tested within approximately 8h post-administration. However, a single dose of MEPH (20 mg) never reached the threshold value (10 microg/mL).