18 December 2012

A practical approach to clincal urine drug testing.


A near ‘holy grail’ status in the eyes of the community has partially eclipsed the useful place of urine drug testing when performed appropriately in the therapeutic milieu. Like DNA testing, the perception of urine toxicology has sometimes moved ahead of its technology.

There is a widely held belief that toxicology results can convict or exonerate, create or dissolve a family union as well as cause a worker to be employed or to be sacked. Doctors who are familiar with toxicology testing may help avert crisis points by using a balanced approach tempered by the usual medical safeguards. It is a conundrum that tests may be ordered by court officials, police, employers and even schools, yet such people are not generally qualified to interpret results and can therefore be prone to serious errors.

The first urine tests to prove clinically useful were probably in Vincent Dole’s classic study on methadone treatment in 1964 [ref 1]. Along with numerous other seemingly obsessive measures, Dole performed daily, witnessed urine tests on his in-patient subjects, proving beyond any criticism that the treatment resulted in favourable drug use outcomes. Paradoxically, at the time opiates could not be detected but instead they tested for quinine, an almost ubiquitous contaminant of street heroin in New York at the time (because its bitterness balanced the sugar used for ‘cutting’ the illicit heroin).


Whenever questions are raised about drug or alcohol use affecting a patient’s life, work or family a ‘spot urine’ test can be very useful. It can be done in the same way as a urine culture, and by the same lab under normal Medicare billing. The usual rules of informed consent should apply and patients should be reminded of the possible consequences, positive and negative in their own circumstances. If one is considering treatment or referral for a drug or alcohol issue a urine test is essential as a base-line. Like other blood tests or X rays, one sometimes orders them just because of some clinical doubt, again with consent. “I think that a urine drug screen might look good for the records … what do you think about that?” This question and any response can be a useful clinical exercise in itself. “What do you think a toxicology test would show right now?” “Well, actually Doc I was going to tell you …”.

Urine testing can be crucial in cases where child custody is involved. Likewise with driving, work safety or sports competition, a urine test or series of tests in the course of normal clinical practice can sometimes influence matters very significantly in the patient’s interests.

Patients who are taking quantities of opioid analgesics for chronic pain should have urine screening performed occasionally [ref 2]. This is a safeguard for both patient and doctor and is described as a part of ‘universal precautions’.


Attempts to make urine testing forensically rigorous include: (1) ID checking and witnessing the sample being produced; (2) ‘chain of custody’ procedures for transporting the sample to the laboratory; (3) parallel second sample for checking (either to the patient or a third party); (4) tests for adulteration. These procedures are only needed for ‘life and death’ or ‘safety critical’ situations. Doctors are familiar with such procedures in the case of blood transfusion cross-matching, for example, where mistakes could be life threatening. So for child custody cases, drug court convictions or employment dismissals such rigour is also required. However, as an aid to clinical medicine it is perfectly satisfactory to perform a ‘spot’ urine test at the surgery or clinic. A degree of supervision and a degree of ‘randomness’ can make the results more ‘dependable’ but neither is necessary on every occasion. Tests for adulteration are now routinely performed including creatinine levels to detect dilution. Low measured levels of a drug may become undetectable on a more dilute specimen. Some vitamins or other chemicals such as soap have been tried to inhibit certain assays.

Laboratory procedures vary widely and one should be familiar with what is offered locally. Most labs have a standard battery of immunoassays for common drugs of abuse such as opiates, cocaine, benzodiazepines and stimulants. Where necessary a confirmation may be performed, generally by ‘GCMS’ (gas chromatography mass spectrometry). In our service we have stopped testing for cannabis except in specific cases of cannabis dependency.


The common qualitative immunoassay for opiates is highly sensitive but not very specific. Hence we usually expect a confirmation for positives using more specific assays for codeine and morphine at least. Morphine can and is metabolised from codeine and yet it may also come from common analgesic combinations and even poppy seeds. Recent use of quantitative measures can help distinguish over-the-counter codeine from heroin/morphine. However, there are traps for the unwary since codeine ‘recovery’ from the usual glucuronide metabolite is highly variable. In addition, people may have taken codeine as well as morphine or heroin (di-acetyl morphine), complicating matters still further. Specific stimulants can usually be detected using modern testing, including amphetamine, metamphetamine (also known as methamphetamine) and MDMA (ecstasy).

By far the most useful result is a negative one. This indicates that the patient was highly unlikely to have used any drugs of abuse in the previous 4 to 6 days. This almost excludes drug dependence but does not exclude casual or binge drug use.


Some may find it surprising that people with no medical training are able to order pathology tests. The matter was raised again recently when an American college introduced mandatory urine testing for all students [ref 3]. While the request may be simple, the interpretation is rarely a simple matter, as shown by media exposés of anomalies, mistakes and sometimes even fraud. Furthermore, it remains to be proven whether there are more benefits or harms resulting in such groups. Should the medical profession become involved? Nobody is better qualified yet many of us may still feel uneasy about such interpretations. Yet interpretation is just a matter of fundamental pharmacology and chemical toxicology so that we should not need to second-guess the outcomes. Where there is any doubt, guilt should not be assumed. Yet in some situations the onus is put onto citizens to ‘prove’ that they are drug-free (as if a single test could prove that). As with the hangman of old, it should never be a doctor’s role to ‘convict’ a patient: if we cannot speak in their defence we should be silent in my view.

As with other pathology ‘group tests’ each lab will do a certain number of agreed tests with or without confirmation. There will be ‘cut-off’ levels quoted for each drug tested with a positive or negative result given. These may change over time and it is important to keep up to date with testing procedures to avoid errors, especially when comparing results from different labs.


A common scenario is a positive test for opiates and amphetamine-type stimulants in a person who claims to have taken no such drugs at all. On closer questioning over-the-counter cold and ‘flu medicines or even poppy seeds can and do cause positive tests. While selective confirmatory testing can sometimes distinguish these, doubts may remain about the origin of, say, morphine. Such doubts must never be allowed to disadvantage a worker, driver, parent or (especially) a school child.

The science of driver testing for alcohol has taken 20 years to get to its present state so it is not surprising that there are still anomalies and ignorance regarding testing for other drugs. In contrast to the close direct relation between alcohol levels and clinical intoxication, cannabis and diazepam, for example, are detectable many days after exposure and levels may bear little relation to ‘sobriety’. Hence a positive test for these drugs is of little relevance to driving or work performance and may just be a needless invasion of the person’s privacy.

Other special cases might be pethidine, buprenorphine and growth hormone. These are difficult to detect using normal techniques although they are of limited relevance in the normal clinical setting. Research for pharmaceutical compliance/adherence often depends upon urine testing although saliva and hair can also be used, the latter with its own ‘time capsule’ drug history.


We must not lose sight of the fact that this is just another pathology test, subject to all the same familiar faults, flaws and limitations. Thus if used selectively with appropriate interpretation, such testing can have a valuable place but should never be seen as a panacea.

Written by Andrew Byrne, Redfern GP specialising in dependency medicine.


1. Dole VP, Nyswander ME. A medical treatment for diacetylmorphine (heroin) addiction. JAMA 1965 193:646-50

2. Heit HA, Gourlay DL. Urine drug testing in pain medicine. J Pain Symptom Management. 2004 27;3:260-7

3. http://www.nytimes.com/2011/10/11/us/at-linn-state-technical-a-fight-over-required-drug-tests.html?hpw New York Times 11/10/11

Reading list:

Clinical Drug Testing in Primary Care. Technical Assistance Publication Series TAP32. SAMHSA 2012  http://kap.samhsa.gov/products/manuals/pdfs/TAP32.pdf

Tenore PL. Advanced urine Toxicology testing. Journal of Addictive Diseases 2010 29:436-448

Chermack ST, Roll J, Reilly M, Davis L, Kilaru U, Grabowski J. Comparison of patient self-report and urinalysis results obtained under naturalistic methadone maintenance conditions. D&A Dependence 2000 59:43-49

Fellous J, Lowenstein W, Gourarier L, Bonan B, et al. Relevance of urinalysis monitoring of methadone maintenance patients: a clinical-biological agreement on 41 patients. Addiction Biology 2000 5:313-318

Cone EJ, Lange R, Darwin WD. In vivo adulteration: excess fluid ingestion causes false-negative marijuana and cocaine urine test results. J Anal Toxicol. 1998 22;6:460-73

Goldstein A, Brown BW. Urine testing in methadone maintenance treatment: applications and limitations. J Substance Abuse Treatment 2003 25;2:61-63

This article on urine testing in clinical practice was commissioned by Australian Prescriber (NPS) but rejected by their editorial team for unspecified reasons. The present article has some minor changes since the original submission. 

Written by Andrew Byrne, General Practitioner and Dependency Specialist.

A colleague in England has suggested that we should broach the area of hair testing as well so I am grateful to Dr Colin Brewer for the following observations:

It may be useful to consider the testing of other body fluids (eg. saliva) and also hair.

For people on amphetamine maintenance, it is possible to tell by analysis of the isomers on hair testing whether the patient is also using street amphetamine.

‘Doctor addicts’ are sometimes very cunning about using alternative or ‘custom’ opiates that don't show up in conventional screening, including pethidine, buprenorphine and fentanyl.

Hair testing has two big advantages. It can reveal occasional use, eg at weekends between regular testing or when patients have to be away for a while such as overseas workers, military folk or airline staff. Also, and uniquely, if there is doubt about a sample, the test can usually be retrospectively repeated on a second sample unless the subject has had a recent and very short haircut. Conversely, for a patient who normally has visible hair suddenly to become a skinhead when hair testing is mentioned is deeply suspicious, especially if they shave their armpits and private regions as well (although the eyelashes usually remain in such cases).

Due to the time frame involved, a mooted hair test can be helpful in the scenario of: 'well, actually doctor, I was going to tell you...'. Furthermore, the increased likelihood of detection can also act as a deterrent to illicit or irregular use when hair testing is being used at some frequency.

For alcohol, hair can now be used to detect occasional use by measuring ethyl glucuronide and similar compounds. This, too, has a strong deterrent effect against occasional use - as with other drugs - thus making such testing therapeutic as well as diagnostic.

In practical terms only one Australian centre can do this test commercially at present (in Adelaide) and it costs about $600 per test, regardless of the length of hair (1-3cm = 1-3 months approx). There is no Medicare rebate for this test so it is usually only useful for proving abstinence where important family court, road traffic or employment matters may hinge on such evidence.

[latter on hair testing written by regular BMJ columnist and London psychiatric consultant Dr Colin Brewer]