Drug Toxicology

Sample type

The RIE Clinical Biochemistry department provides a pan-Lothian testing service. Testing can be carried out on oral fluid swabs and urine samples. Oral fluid swabs are the test of choice and recommended by the specialist services. They are quicker and have the advantage of witnessed collection which avoids sample swapping or adulteration.

It is useful to indicate on the request form which relevant drugs the patient is prescribed.

Oral fluid

How to collect saliva using the Sarstedt Salivette device:

Remove the top cap of the tube to expose the round sponge. Do not remove the holder that the sponge sits in.
Place the sponge in your mouth by tipping the tube so the sponge falls into your mouth. Do not touch the sponge with your fingers.
Keep the sponge in your mouth. Very gently chew and roll the sponge around your mouth for 1-2 minutes. Spit the sponge back into the inner sleeve of the tube. Do not touch the sponge with your fingers.
Replace the cap. Make sure cap is on tightly.
GPOC / ICE orders can be found under Common Tests, Drug Screening. Otherwise, label the Salivette tube with the patient’s full name, date of birth and date of collection. Complete all details on the request form, including full name, date of birth, CHI or registration number, postcode (if CHI not available), requesting location and clinician, time/date of collection and specimen type, requesting a drug screen.

Note

Testing requires 50µl of saliva. Approximately 4% of received samples are insufficient so it is important that the swab is gently chewed for 2 full minutes to ensure sufficient saliva is collected.
Samples should not be collected within an hour of a drug being administered orally since these can contaminate the oral mucosa leading to extremely high concentrations in the sample which can cause analytical issues both for this, & subsequent, samples. This is particularly relevant for all oral buprenorphine preparations.
If a patient has very recently taken medication or another drug orally, consider postponing the test or sending a fresh urine sample instead.

Urine

Take a spot urine sample into a white top, plain universal container.
GPOC / ICE orders can be found under Common Tests, Drug Screening. Otherwise, label the Salivette tube with the patient’s full name, date of birth and date of collection. Complete all details on the request form, including full name, date of birth, CHI or registration number, postcode (if CHI not available), requesting location and clinician, time/date of collection and specimen type, requesting a drug screen.

Note

An advantage of urine testing is the relatively longer duration of detectability since drug metabolites are often the compounds of interest.
Sample integrity checks include creatinine measurement to determine if pale samples are dilute (<2.0 mmol/L) and therefore prone to false negative results. Dilute samples will be highlighted on the report.

Drug repertoire

The toxicology lab currently tests for approximately 25 drugs and metabolites in oral fluid and urine in every sample. Please note that cannabis can be tested in urine but is not part of the core panel of drugs and must be ordered separately (on GP ICE ‘Urinary drugs of abuse + cannabis’ or with a hand written form)

Toxicology reports contain 10 core groups. These include recently added ketamine, xylazine and nitazene groups:

Group	Notes
Opiate group	Morphine, codeine and 6MAM (heroin metabolite) Dihydrocodeine, oxycodone (individual drugs only reported when group is positive
Amphetamine
Cocaine	Or metabolite, benzoylecgonine, in urine
Methadone	Or metabolite (EDDP) in urine
Benzodiazepine group	Includes diazepam, temazepam, nitrazepam, nordiazepam (metabolite of diazepam and chlordiazepoxide) and 7-aminoclonazepam (urine only) Individual drugs are not reported
Gabapentin
Pregabalin
Buprenorphine	Or norbuprenorphine (buprenorphine metabolite) in urine
Ketamine	Norketamine (ketamine metabolite) will be measured but not reported
Xylazine
Nitazene group	Includes Isotonitazene, Metonitazene, N-Pyrrolidino Etonitazene, Protonitazene

The following drugs are tested in every sample but only reported when positive ie. if these are not listed on the report, a negative result can be assumed.

DRUG	Notes
MDMA	Ecstasy
Methamphetamine
Tramadol
‘Street’ Benzodiazepines	Includes Alprazolam (Xanax), Etizolam, Bromazolam

Opiate metabolism – points to note:

Morphine may be derived from morphine preparations (e.g. MST or Oramorph), heroin or codeine.
6MAM is derived only from heroin, so indicates heroin use.
Dihydrocodeine does not metabolise to, or from, codeine.
Oxycodone may be derived from drugs containing it (e.g. OxyNorm, OxyContin).

Interpreting and acting on results

Results are normally available within 7 days and often after 3-4 days. Contact the laboratory if results are required sooner but quicker turnaround time cannot be guaranteed.
Inconsistent or unexpected results should always be interpreted in view of other clinical information and should not be treated as definitive in isolation.
If an unexpected positive or negative result is received, contact the laboratory as soon as possible – further review and/or repeat analysis may clarify the situation.
Results should not be used for medicolegal purposes.

Positive and negative results – General points to note:

Many prescribed and illicit drugs can be misused, but not all can be identified by current testing due to the rapidly evolving nature of novel psychoactive substances. Drugs may be present in the sample but not reported as positive because the drug is not included in the panel.
The method is mass spectrometry based which is highly specific for the drugs included in the panel and therefore not prone to false positives. There is a very high degree of assurance positive results are reliable due to the nature of the method and quality checking processes.
A negative result may occasionally be reported at low doses of methadone (less than 10-15 mg/day), in pregnancy or if the patient is a fast metaboliser of methadone.
Negative results can be seen in some patients on low dose (8 mg/day) buprenorphine particularly if the sample is collected more than 10 hours after a dose.
Long-acting injectable buprenorphine (Buvidal) may produce false negative results on oral fluid testing, especially at relatively low dose.

Duration of Detectability

Drugs have a duration (or ‘window’) of detectability which is the period after drug administration that would be expected to produce a positive result on testing. These should only be used as a rough guide and vary depending on a number of criteria including the drug type, dose, pattern of consumption, route of administration, sample type and individual pharmacokinetics (metabolism, saliva pH).

The table below shows approximate durations of detectability (NB published evidence in this area is limited):

Drug	Approximate duration of detectability
Drug	Oral fluid	Urine
Opiates*	24 hours	48 hours
Cocaine*	24-48 hours	48-72 hours
Benzodiazepines**	< 7days	7 days
Methadone	<7 days	7 days
Buprenorphine	<4 days	4-6 days
Amphetamine Metamphetamine MDMA (‘Ecstasy’)	24 hours	48 hours
Gabapentin Pregabalin	<48 hours	48 hours
Tramadol	<48 hours	48 hours
Cannabis	N/A	4 weeks or longer in chronic, heavy use

*Some studies have suggested that 6MAM (heroin metabolite) and cocaine may be detectable up to 5 days in oral fluid (longer than in urine) in high dose, long term users.

**Clearance rates of benzodiazepines vary (‘long-acting’ diazepam and chlordiazepoxide may be detected for up to 7 days whereas ‘short-intermediate acting’ drugs such as alprazolam and etizolam may be present for only 24-48 hours).