Purpose: Pharmacological, pharmacokinetic; to compare drug concentrations in various biological fluids (blood, sweat, saliva and urine) over a 5 hour period after drug administration.

Design: Randomized double-blind cross-over (within subjects) experimental design with time of sample collection (0, 1, 2, 3, 4 or 5 h post-drug) serving as within-subject variable. Values were not compared between MDMA and placebo sessions in this publication. All participants received either placebo, 75 mg MDMA or 0.5 g/kg ethanol in 3 separate sessions scheduled 2 weeks apart, with all samples of blood, saliva, sweat and urine collected from all participants.

Subjects: 12 MDMA-experienced volunteers (8 men, 4 women, ages 21-30), probably residing in or near Groningen (the Netherlands). No information is provided on recruitment of participants.

Criteria for Inclusion - Having used ecstasy, with minimum use not reported, abstinence from all psychoactive drugs save ethanol for 2 wks prior to study day, with abstinence verified through urinary analysis, abstinence from ethanol for 1 day prior to study day, with abstinence verified through assessment of breath alcohol content, and healthy, without specifying manner in which health was confirmed.

Measures: Plasma - Blood was collected at 60 min intervals (0, 1, 2, 3, 4 and 5 h post-drug), and MDMA and MDA concentration measured via gas chromatography-mass spectrometry (GC-MS-EI)

Urine - Urine samples were collected at 60 min intervals (0, 1, 2, 3, 4 and 5 h post-drug, or presumably around these time points), and urinary content of MDMA was assessed with GC-MS-EI

Saliva - Oral fluid was collected at 60 min intervals (0, 1, 2, 3, 4 and 5 h post-drug), and MDMA concentration assessed via reverse phase high performance liquid chromatography (HPLC-MS).

Sweat - Sweat was collected via wiping at 60 min intervals (0, 1, 2, 3, 4 and 5 h post-drug), and MDMA concentration in sweat was assessed with HPLC after extracting substances from sweat wipe with methanol.

Analyses: No statistical analyses are described. Average measurement of MDMA concentration in each biological fluid at each time point was computed and presented in charts and tables, and non-statistical comparisons are made across biological fluids at different points in time. A correlation was performed between individual plasma MDMA concentrations and oral fluid (salivary) MDMA concentrations over time. Peak concentration values were also computed.

Results: Plasma - Plasma MDMA concentrations collected from 0 to 5 h post-drug ranged from 21 ng/ml to 295 ng/ml and peak values were recorded 2 to 4 h post-drug, with average value being 178 +/- 52 ng/ml. MDA concentration at each point in time never exceeded 20 ng/ml.

Urine - MDMA levels in urine collected from 0 to 5 h post-drug ranged from 0.32 mg/g creatine to 50 mg/g creatine, with mean urinary MDMA value being 13 +/- 8 mg/g creatine. At 0 h post-drug, only 1/12 had detectable amphetamines in urine (0.16 mg/g creatine MDMA). No peak urinary MDMA values are provided.

Saliva - Salivary MDMA content collected from 0 to 5 h post-drug ranged from 50 to 6982 ng/ml, with intersubject variation in salivary MDMA 3 times greater than inter-subject variation in plasma MDMA concentrations. Peak salivary MDMA values were achieved 2 to 3 h post-drug, with peak value being 1215 +/- 944 ng/ml MDMA.

Sweat - With the exception of readings taken from 2 / 12 participants at two points in time, MDMA concentration in sweat remained below 50 ng/wipe. Average MDMA concentrations across 5 h were 25 ng/wipe. While peak concentration is not reported, examination of figure (Fig. 5) indicates that sweat MDMA concentrations slowly increased over time, with highest levels (approx. 20 and 18 ng/wipe) reached at 4 and 5 h post-drug, probably due to accumulation of excreted MDMA on the skin.

Plasma and Salivary MDMA - There was no significant association between a participant's plasma MDMA value and his or her salivary MDMA value at each individual point in time. Saliva/plasma (SP) MDMA ratios varied within each participant as a function of time of measurement. Examination of figure (Fig. 3) indicates that plasma and salivary values were most closely matched at 2 and 3 h post-drug, and least matched at 5 h post-drug. Maximum SP ratios were reached at 1 h post-drug, and were 12 +/- 6, with SP ratios declining to 4 +/- 3 at 4 to 5 h post-drug.

Overall Effects: After administering 75 mg MDMA to 12 healthy experienced ecstasy users, drug concentrations were successfully measured in plasma, urine, saliva and sweat, though MDMA concentrations in sweat were very low. Peak plasma concentrations of MDMA appeared 2 to 4 h post-drug, and peak salivary MDMA concentrations appeared 2 to 3 h post-drug. MDMA concentration in sweat remained below 50 ng/wipe in all but two individual data points, with sweat MDMA values slowly increasing over time, and highest values recorded 4 and 5 h post-drug. Salivary MDMA varied across participants at 3 times the rate of inter-subject variance in plasma MDMA. The authors hypothesize that this might relate to variance in salivary viscosity. Salivary levels and plasma levels were most similar at 1 h post-drug and least similar at 5 h post-drug. Though no information is provided on subjective effects or side effects in this report, 75 mg MDMA was well-tolerated in this group of participants.

Adverse Effects: None reported in this paper.

Comments: To date, this is the first report wherein MDMA concentrations were assessed from blood, urine, saliva and sweat at approximately the same points in time and in the same sample of participants. The sample size featured in this report is also the largest represented in any study reporting MDMA concentrations in bodily fluids, perhaps with the exception of some pooled analyses reported by the de la Torre team (Pacifici et al. 2002). It is also the first large-scale assessment of MDMA in bodily fluids including both male and female participants. The authors note that study findings are similar to those reported in similar studies (e.g. Mas et al. 1999; Navarro et al. 2001) for plasma, urine and saliva. (Salivary values reported in Navarro et al. (2001) were higher, but dose used in that study was 100 mg.) However, sweat MDMA values appear to be much lower than values collected from people stopped for impaired driving in Belgium, where the sweat MDMA values ranged from 88 to 20,000 ng/wipe. The authors hypothesize that higher sweat MDMA values were caused by contamination by touching the forehead after handling MDMA, and also through the potentially higher doses of MDMA that impaired drivers self-administered. Study limitations include relatively small sample size and lack of analysis by participant weight or gender, and possibly insufficient information concerning participant health. Further research should examine MDMA concentration at points from 5 h onwards, perhaps up to 24 h post-drug.