Table 5.

Possible reasons for the apparent under- and over-detection of drug metabolites.

Drug Metabolite	Possible Reason	Example
Non- identification	The metabolite is not in the platform library	Metabolites of unknown identity, X – 17348 with esomeprazole
Non-detection	The metabolite is not captured by the current LC/MS protocol	Rosuvastatin, reported by 141/6000 participants, but not detected
Under-detection	Blood levels below level of detection (metabolite half-life, timing of sampling)	Atorvastatin
Over-detection	Medication is taken, but not reported	Painkillers, anti-depressants
Over-detection	Carry-over from other samples	Not observed
Over-detection	Misidentification of other molecules (overlapping signals)	Metformin
Ubiquitous	Metabolite is endogenous, supplementation by medication cannot be determined by presence/absence of detection	Levothyroxine, reported by 492/6000 participants