Prescription stimulants split into two families: amphetamine-type agents (amphetamine, dextroamphetamine, lisdexamfetamine, methamphetamine, phentermine, benzphetamine) and methylphenidate-type agents (methylphenidate, dexmethylphenidate). They differ in metabolism and in how they screen: amphetamine immunoassays detect the amphetamine family but not methylphenidate, so LC-MS/MS is needed to identify the specific agent.1
Interpretation requires knowing the family and its metabolites: several amphetamine-type prescriptions produce amphetamine (and some produce methamphetamine), while methylphenidate produces ritalinic acid and is invisible to amphetamine screens. Amphetamine immunoassays are also prone to false positives from unrelated drugs, so a positive should be confirmed.2
LC-MS/MS identifies the specific stimulant and metabolite. Key relationships: benzphetamine can yield methamphetamine and amphetamine, dextroamphetamine and lisdexamfetamine yield amphetamine, and methylphenidate yields ritalinic acid.3 For methamphetamine positives, d/l isomer testing distinguishes illicit from medicinal sources.3
Match analyte to prescription. The detected amphetamine or methylphenidate should fit the prescribed agent's metabolism.3
Screen positives need confirmation. Amphetamine immunoassays cross-react; confirm the specific drug by LC-MS/MS.2
Methamphetamine source. Consider d/l isomer testing to separate illicit from medicinal methamphetamine.
Methylphenidate is missed. A negative amphetamine screen does not exclude methylphenidate use.
Timing and cutoff. Absence may reflect timing of last use, dose, or levels below the cutoff.
Metabolism varies. CYP2D6 and urinary pH shift levels and detection windows.
| Medication (generic) | Measured analyte(s) | Urine window |
|---|---|---|
| Amphetamine (Adderall) | Amphetamine | 2-7 days |
| Dextroamphetamine | Amphetamine | 2-7 days |
| Lisdexamfetamine (Vyvanse) | Amphetamine | 2-7 days |
| Methamphetamine (Desoxyn) | Methamphetamine (+ amphetamine) | 2-7 days |
| Benzphetamine (Didrex) | Methamphetamine, amphetamine | 2-7 days |
| Phentermine (Adipex-P) | Phentermine | 2-7 days (limited data) |
| Methylphenidate (Ritalin/Concerta) | Methylphenidate, ritalinic acid | 1-2 days |
| Dexmethylphenidate (Focalin) | Methylphenidate, ritalinic acid | 1-2 days |
Amphetamine-type agents produce amphetamine (some also methamphetamine); methylphenidate-type produce ritalinic acid and are missed by amphetamine screens.