Duration of detectable methamphetamine and amphetamine excretion in urine after controlled oral administration of methamphetamine to humans.

BACKGROUND: Confirmation of a workplace drug test requires urinary methamphetamine (MAMP) and amphetamine (AMP) concentrations > or = 500 and 200 micro g/L, respectively, but cutoffs at half those values (250/100 micro g/L) have been proposed. We determined the urinary excretion of MAMP after oral ingestion and examined the effect of using lower cutoffs on detection of exposure. METHODS: Volunteers (n = 8) ingested four 10-mg doses of MAMP. HCl daily over 7 days, and five of them ingested four 20-mg doses 4 weeks later. After ingestion, the volunteers collected all urine specimens for 2 weeks. After solid-phase extraction, MAMP and AMP were measured by gas chromatography-positive chemical ionization mass spectrometry with dual silyl derivatization. RESULTS: MAMP and AMP were generally detected in the first or second void (0.7-11.3 h) collected after drug administration, with concentrations of 82-1827 and 12-180 micro g/L, respectively. Peak MAMP concentrations (1871-6004 micro g/L) after single doses occurred within 1.5-60 h. MAMP > or = 500 micro g/L was first detected in the first or second void (1-11 h) at 524-1871 micro g/L. Lowering the MAMP cutoff to 250 micro g/L changed the initial detection time little. AMP > or = 200 micro g/L was first detected in the 2nd-13th (7-20 h) post-administration voids. At a cutoff of 100 micro g/L, AMP was first confirmed in the second to eighth void (4-13 h). Reducing the cutoff to 250/100 micro g/L extended terminal MAMP detection by up to 24 h, increased total detection time by up to 34 h, and increased the total number of positive specimens by 48%. CONCLUSIONS: At the lower cutoff, initial detection times are earlier, detection windows are longer, and confirmation rates are increased. Elimination of the AMP requirement would increase detection rates and allow earlier detection.

Plasma and oral fluid pharmacokinetics and pharmacodynamics after oral codeine administration.

BACKGROUND: The ease, noninvasiveness, and safety of oral fluid collection have increased the use of this alternative matrix for drugs-of-abuse testing; however, few controlled drug administration data are available to aid in the interpretation of oral fluid results. METHODS: Single oral codeine doses (60 and 120 mg/70 kg) were administered to 19 volunteers. Oral fluid and plasma were analyzed for free codeine, norcodeine, morphine, and normorphine by solid-phase extraction combined with gas chromatography-mass spectrometry (SPE/GC-MS). Physiologic and subjective effects were examined. RESULTS: Mean (SE) peak codeine concentrations were 214.2 +/- 27.6 and 474.3 +/- 77.0 micro g/L in plasma and 638.4 +/- 64.4 and 1599.3 +/- 241.0 micro g/L in oral fluid. The oral fluid-to-plasma ratio for codeine was relatively constant ( approximately 4) from 1 to 12 h. The mean half-life (t(1/2)) of codeine was 2.2 +/- 0.10 h in plasma and 2.2 +/- 0.16 h in oral fluid. Significant dose-related miosis and increases in sedation, psychotomimetic effect, and "high" occurred after the high dose. Mean codeine oral fluid detection time was 21 h with a 2.5 microg/L cutoff, longer than that of plasma (12-16 h). Detection times with the proposed Substance Abuse and Mental Health Services Administration cutoff (40 microg/L) were only 7 h. Norcodeine, but not morphine or normorphine, was quantified in both plasma and oral fluid. CONCLUSIONS: The disposition of codeine over time was similar in plasma and oral fluid, but because of high variability, oral fluid codeine concentrations did not reliably predict concurrent plasma concentrations. Oral fluid testing is a useful alternative matrix for monitoring codeine exposure with a detection window of 7-21 h for single doses, depending on cutoff concentrations. These controlled drug administration data should aid in the interpretation of oral fluid codeine results.

Methamphetamine and amphetamine pharmacokinetics in oral fluid and plasma after controlled oral methamphetamine administration to human volunteers.

BACKGROUND: Methamphetamine (METH) and amphetamine (AMP) concentrations in 200 plasma and 590 oral fluid specimens were used to evaluate METH pharmacokinetics and pharmacodynamics after oral administration of sustained-release METH. METHODS: Eight participants received four oral 10-mg S-(+)-METH hydrochloride sustained-release tablets within 7 days. Three weeks later, five participants received four oral 20-mg doses. Blood samples were collected for up to 24 h and oral fluid for up to 72 h after drug administration. RESULTS: After the first oral dose, initial plasma METH detection was within 0.25-2 h; c(max) was 14.5-33.8 micro g/L (10 mg) and 26.2-44.3 micro g/L (20 mg) within 2-12 h. In oral fluid, METH was detected as early as 0.08-2 h; c(max) was 24.7-312.2 micro g/L (10 mg) and 75.3-321.7 micro g/L (20 mg) and occurred at 2-12 h. The median oral fluid-plasma METH concentration ratio was 2.0 across 24 h and was highly variable. Neutral cotton swab collection yielded significantly higher METH and AMP concentrations than citric acid candy-stimulated expectoration. Mean (SD) areas under the curve for AMP were 21% +/- 25% and 24% +/- 11% of those observed for METH in plasma and oral fluid, respectively. After a single low or high dose, plasma METH was >2.5 micro g/L for up to 24 h in 9 of 12 individuals (mean, 7.3 +/- 5.5 micro g/L at 24 h); in oral fluid the detection window was at least 24 h (mean, 18.8 +/- 18.0 micro g/L at 24 h). The plasma and oral fluid 24-h METH detection rates were 54% and 60%, respectively. After four administrations, METH was measurable for 36-72 h (mean, 58.3 +/- 14.5 h). CONCLUSIONS: Perceived advantages of oral fluid for verifying METH exposure compared with urine include simpler specimen collection and reduced potential for adulteration, but urine offers higher analyte concentrations and a greater window of detection.