Amphetamine Metabolites Detectable in Urine Following Adderall Administration
Adderall is excreted primarily as unchanged amphetamine in the urine, with up to 80% appearing as the parent compound rather than metabolites. 1
Primary Urinary Findings
The predominant finding in urine drug testing after Adderall use is unchanged amphetamine (both d- and l-enantiomers), not metabolites. 1 This is because amphetamine undergoes minimal metabolism, with the majority being excreted unchanged through the kidneys. 1
Enantiomer Composition
- Adderall contains a 3:1 ratio of d-amphetamine to l-amphetamine salts, and this enantiomeric mixture is detectable in urine. 2, 3
- The d-enantiomer predominates initially after dosing, with the proportion of l-enantiomer increasing over time due to differential metabolism rates. 2, 3
- Detection of the l-enantiomer is pathognomonic for Adderall use (or other mixed-salt formulations), as pure dextroamphetamine preparations and most illicit amphetamine contain only the d-enantiomer. 2, 3
Detection Parameters
Concentration and Duration
- Peak amphetamine concentrations in urine range from 2,645 to 5,948 ng/mL after a single 20-mg dose, and from 5,739 to 19,172 ng/mL with repeated daily dosing. 2, 3
- Amphetamine remains detectable above the 500 ng/mL confirmatory cutoff for up to 47.5 hours after a single dose and up to 60 hours after the last dose of a multi-day regimen. 2, 3
- The drug can be detected at trace levels (≥5 ng/mL) for even longer periods. 2, 3
Important Testing Considerations
- Not all samples containing ≥500 ng/mL total amphetamine test positive on immunoassay screening due to differing cross-reactivity of the d- and l-enantiomers with antibodies used in screening tests. 2, 3
- Drug concentration profiles are highly variable both within and between individuals due to urine dilution and pH fluctuations. 2
- Methylphenidate is NOT detected on routine amphetamine panels, so a positive amphetamine result cannot be explained by methylphenidate use. 1, 4
Metabolic Pathways (Minor Components)
While the guideline evidence emphasizes that amphetamine is predominantly excreted unchanged, the metabolic pathways mentioned include: 1
- p-Hydroxylation
- N-Demethylation
- Deamination
- Conjugation
However, these pathways account for only a small fraction of elimination compared to renal excretion of unchanged drug. 1
Clinical Pitfalls
- Standard immunoassay screening tests are presumptive only and require gas chromatography-mass spectrometry (GC-MS) confirmation, particularly when results will impact clinical decisions. 1, 4
- Enantiomer-specific analysis using GC-MS can definitively distinguish Adderall use from other amphetamine sources by detecting the characteristic l-enantiomer. 2, 3
- Pseudoephedrine in over-the-counter cold medications can cause false-positive amphetamine results on screening tests. 1, 4
- The presence of amphetamine in urine cannot distinguish between appropriate therapeutic use and misuse of prescribed Adderall. 4