What the lab can and cannot do: clinical interpretation of drug testing results

Figures & data

Table 1. Drug half-lives and approximate urine detection periods.

DRUG	Half-life^a (t½)	Detection period^b	Comments
Alcohol (Ethanol)	Blood concentration falls by an average of 3.2–3.9 mmol/L/h OR 15–18 mg/100 ml/h in social drinkers Can be much higher in heavy drinkers (BMK data: 6.5 mmol/L or 30 mg/100mL/h)	Few to many hours depending on amount of alcohol consumed Urine: 1–2 h after BAC reaches zero	Alcohol elimination follows zero order kinetics. During absorption phase, urine level lags behind blood concentration i.e. BAC is higher than UAlc. iii). During elimination phase, BAC lags behind urine concentration i.e. UAlc is higher than BAC.
Ethyl Glucuronide (EtG)	2.6–4.3 h	Depends on amount of ethanol use.	0.02% of ethanol is excreted as EtG.
Ethyl Sulfate (EtS)	2.7–5.4 h	Depends on amount of ethanol use.
Phosphatidylethanol (PEth)	3–4 days		Venous blood should be obtained in an EDTA coated tube.
Amphetamine	7–34 h	2–3 days	If EIA is positive, confirmation by chromatography is required because of high incidence of false positives. EIA cross-reacts with phenylpropanolamine, ephedrine, pseudoephedrine, bromphenriamine, bupropion, tradazone, chlorpromazine, promethazine and ranitidine.
Methamphetamine	12–34 h	2–3 days
Methlyenedioxy methamphetamine (MDMA) (aka Ecstasy)	7.6 h	2–3 days	MDMA and MDA will be positive with the new generation Ecstasy EIA assay but will also cross-react with amphetamine derivatives as in (ii) above.
Barbiturate (Phenobarbital)	35–120 h	1 to 2 weeks after last use (Phenobarbital)	Chromatography required to differentiate between various barbiturates.
Benzodiazepines	Few hours to days	Days to weeks (depending on half-life)	EIA does not differentiate between different benzodiazepines. Chromatography required to differentiate different benzodiazepines. Some short acting agents have poor EIA sensitivity. Oxaprozin (Daypro) and Diminhydranate (Gravol can cause a false positive.
Alprazolam	12–15 h
Chlordiazepoxide	10–30 h		sertraline (Zolof) can cause false positive
Diazepam	20–80 h	≥2 weeks after last chronic use of diazepam
Clonazepam	10–50 h	Poor to not detected 122% cross reactivity but dosage very low	Extensively bio-transformed, less than 0.5% excreted in urine over 24 h. Sometime visible on hydrolysis and GCMS if chronic dosing is involved.
Flunitrazepam (date rape drug Rohypnol)^c	18–26 h	Not differentiated by immunoassay	Need to test for the amino derivative of flunitrazepam by chromatography.
Bromazepam	20–30 h		Extensively metabolized. 2% excreted unchanged in urine. To avoid false-negative EIA, GC-MS screening for 2- amino-3-hydroxy-5-bromobenzoylpyridine is recommended.
Lorazepam	10–20 h		In hydrolyzed urine: GCMS can differentiate between lorazepam and other benzodiazepines.
Cocaine	0.5–1.5 h	Few hours	Cocaine not detected by EIA, but detected by chromatography.
Benzoylecgonine (BEG) (metabolite of cocaine)	5–7 h	3–5 days	BEG detected by EIA and chromatography.
Gamma-Hydroxybutyrate (GHB) (date rape drug)	0.3–1.0 h	<12 h	Chromatography required. Detected as GHB lactone.
Gabapentin	5–7 h		Not significantly metabolized.
Pregabalin	5.3–6.3 h
Opiates^d	1.3–6.7 h	2–4 days	Chromatography is required to identify specific opiates (e.g. codeine, oxycodone, hydrocodone). Even one poppy seed bagel will give an opiate positive result.
Heroin	2–3 min		Not tested in urine.
6-Mono-acetyl-morphine (MAM)	∼30 min	Few hours	Detected by EIA and chromatography.
Morphine	2–3 h	∼72 h	A small amount of morphine is bio-transformed into hydromorphone but not to Oxymorphone. 75% of morphine is eliminated as M3G and less than 10% as unchanged morphine.
Codeine	2.5–3 h		About 10% of codeine is metabolized to morphine in normal metabolizers.
Hydromorphone	2–3 h		A small amount of morphine is biotransformed to hydromorphone but not Oxymorphone.
Hydrocodone	3.8–6 h	98 h
Oxycodone	4–6 h		Oxycodone half-life increases with age. 33-66% of single dose eliminated in 24 h. Chromatography required to identify oxycodone, oxymorphone and other metabolites. iOxymorphone not detected by opiate immunoassay. Large amount of oxycodone may give positive on some opiate immunoassays.
Oxymorphone	6–9 h
Meperidine	2–5 h		Chromatography required.
Fentanyl^e	IV = 2.5 min, Intranasal = 6.5 min, Transdermal patch = 7 h (3–12 h)		EIA now available. Chromatography will identify both fentanyl and nor-fentanyl.
Methadone	15–40 h 27 ± 8 h^f in chronic users	1–4 days Urine should always be positive in chronic users	At alkaline pH methadone is reabsorbed in the kidney. Chromatography or specific EIA required to distinguish methadone from its metabolite, EDDP. Diphenhydramine, clomipramine, Phenylpropanolamine, chlorpromazine, quetiapine and thioridazine, verapamil have been reported to cause false positive.
EDDP (Methadone metabolite)	Similar to methadone	Urine should always be positive in chronic users^g	EDDP not affected by urine pH, making it a better marker for compliance monitoring.
Buprenorphine	Parental = 2–4 h Sublingual = 19–49 h	Urine should always be positive in chronic users^g	Depending on the EIA used, there is cross reactivity from structurally unrelated compounds such as chloroquine and HO-chloroquine. Sulpiride amisulpride have given false positive.
Tramadol	2 h ∼9.3 h in overdoses	2–3 days
δ^9-Tetrahydrocannabinol (THC) Marijuana	14–38 h	blood levels fall by 90% in 1 h	Parent drug not detected in urine.
δ^9-Tetrahydrocannabinoic acid (marijuana metabolite in urine)	Days to weeks in chronic users	Few days to many weeks depending on chronicity of use	Detected as “cannabinoids” by EIA. False positive reported (NAIDS naproxen and ibuprofen)
Phencyclidine (PCP)	7–16 h	2–3 days	Positive incidences are very rare. Many immunoassays give a false positive for PCP.

^aR.C. Baselt: Disposition of Toxic Drugs and Chemicals in Man, Ninth Edition 2011.

^bThe detection period is very much dose and half-life dependent. The larger the dose, the longer the period the drug/metabolite may be detected in the urine.

^cFlunitrazepam (Rohypnol) is usually not detected with the generic EIA benzodiazepine procedure. Use chromatography to detect Amino-Flunitrazepam.

^dOpiates may be positive for up to 2 weeks after last use with slow release opiates.

^ePatients on transdermal patch will show positive for the duration for the patch.

^fMethadone half-life reported in literature. Author (BMK) studies on chronic users in methadone maintenance treatment program.

^gBoth buprenorphine and methadone are prescribed on chronic basis and have half-lives of >24 h. Under these condition drugs blood levels will reach a steady state. Urine samples from patients on chronic dosing should always be positive.

Figure 1. Cocaine and Opiate use profile. Following urine concentrations can show new drug use occurred.

Figure 2. Urine specific gravity vs Urine creatinine. Numerous urine creatinine concentrations are possible for every specific gravity value, suggesting urine creatinine is a better marker of dilution.

Table 2. Descriptive statistics for urine reference ranges.

	n	Mean	Min	Max	Std Dev	95% Reference Range
pH	5464	5.9	5.0	9.0	0.92
Cr (mmol/L)	5477	11.6	0	50.2	6.5	>2
Na (mmol/L)	5474	115	6	353	56	20-230
Cl (mmol/L)	5474	130	7	374	62	15-250

Figure 3. Urine EDDP (methadone metabolite) profile. EDDP excretion window is at “steady state” in patients on chronic dosing. Non-adherence or problem samples can be identified. UCr does not add value to interpretation.

Figure 4. Alcohol blood and urine profile. The blood alcohol concentration and urine alcohol concentration curves are displaced in time as there is time lag in the production and diffusion of alcohol into the bladder.

Table 3. Urine glucose stability in a diabetic patient NOT drinking alcohol.

Day Number	Room temperature			Fridge temperature (4ºC)
	Alcohol	Glucose	EtG	Glucose	Alcohol	EtG
	(mmol)	(mmol)	(ng/mL)	(mmol)	(mmol)	(ng/mL)
0	7.3	49.2	0
1	8.8	48	2	50	6.5	.8
4	52.7	33	2	50	4.9	0
5	53.6	33	2	51	6	0
6	57.1	30	2	49	5.8	2

In a diabetic patient not drinking alcohol, glucose decreases and alcohol increases with time. No change (negative) in EtG concentrations.

EtG: Ethylglucuronide.

Table 4. Urine glucose stability in a diabetic patient who has been drinking alcohol.

Day Number	Room temperature			Fridge temperature (4 °C)
	Glucose	Alcohol	EtG	Glucose	Alcohol	EtG
	(mmol)	(mmol)	(mg/L)	(mmol)	(mmol)	(mg/L)
0	287	7.6	42.94
4	279	16.5	44.06	295	8.0	44.02
5	255	25.5	45.41	288	8.1	45.21
6	248	27.5	44.92	288	8.2	42.03
7	232	27.3	44.39	280	8.2	43.62
8	237	26.3	42.55	278	8.0	39.94

In a diabetic patient drinking alcohol, glucose decreases and alcohol increases with time. Urine is positive for EtG.

EtG: Ethylglucuronide.

Figure 5. Cocaine metabolism. All chemical formulas are from their respective pages in Wikipedia.

Figure 6. Opiate metabolism. All chemical formulas are from their respective pages in Wikipedia.

Table 5. Effect of urine pH on methadone excretion.

Methadone EIA Results	Urine pH	Urine Cr (mmol/L)	Methadone dose (mg/day)
Negative	8.5	6.5	140
Negative	8.5	6.7	100
Positive	8.5	16.7	100
Negative	8.5	9.5	70
Negative	7.0	3.4	100
Negative	8.0	1.5	105
Negative	8.5	6.5	80
Negative	8.5	4.5	40

At alkaline pH, methadone is reabsorbed, and EIA results can be negative even at high mg/day dose.

Figure 7. Calculation of methadone half life. In a once a day (24 h) dosing. C4h (C _{post peak}) must be measured 4 or more hours after last dose to ensure drug distribution has taken place.

Figure 8. Urine EDDP (methadone metabolite) and change in methadone dose. Urine EDDP concentrations fall in tandem with decreasing methadone dose.

Figure 9. Oxycodone dose and urine EIA profile. Although oxycodone dose (mg/day) is increasing, oxycodone (ng/mL) concentrations are inconsistent with dose change. Following urinary ng/mL can show non-adherence to dose changes.