Qualitative urinalysis can verify abstinence of drug misuse but cannot detect changes in drug intake. For drugs with slow elimination, like methamphetamine (MA), a single episode of abuse can result in up to 5 days of positive urine drug screens. Thus, interventions that produce substantial decreases in drug use but do not achieve almost complete abstinence are classified as ineffective. Using non-pharmacologic doses of deuterium-labeled l-methamphetamine (l-MA-d3) we have developed a simple, robust method that reliably estimates changes in MA intake. Twelve subjects were dosed with 5 mg l-MA-d3 daily and challenged with 15, 30 and 45 mg of non-labeled d-MA (d-MA-d0) after reaching plasma steady status of l-MA-d3. Urinary concentration ratios of d-MA-d0 to l-MA-d3 provided clear separation of the administered doses with as little as 15 mg dose increments. Administered doses could not be resolved using d-MA-d0 concentrations alone. In conclusion, the urinary [d-MA-d0 ] : [l-MA-d3] provides a quantitative, continuous measure of illicit MA exposure. The method reliably detects small, clinically relevant changes in illicit MA intake from random urine specimens, is amenable to deployment in clinical trials, and can be used to quantify patterns of MA abuse.
- Received January 11, 2011.
- Revision received March 25, 2011.
- Accepted March 28, 2011.
- The American Society for Pharmacology and Experimental Therapeutics