Drugs of Abuse Guidelines

Copyright ^© [Regional Laboratory for Toxicology] 2007. All rights reserved.

Table of Contents

INTRODUCTION

This guide has been written for medical, nursing and support staff who deal with patients or clients who have "drug problems". It is a description of the investigations currently available from the Regional Laboratory for Toxicology. Careful thought should go into making a laboratory request with regard to the scope and frequency of any investigations.

Screening for drugs of abuse (as distinct from the investigation of volatile substance abuse) is carried out with urine specimens. A wide variety of drugs will be detected qualitatively by the "standard" screening procedure. However, some other substances of abuse are not sought routinely (Table 1), and in these cases, the laboratory test which is relevant should be requested specifically.

It should be noted that analysis of urine specimens for "drugs of abuse" will only give information about current or recent drug usage. A specimen taken more than a few days after an episode of 'abuse' is likely to be negative on screening for most substances, with the notable exception of cannabis.

The range of substances detected in the "standard" screening procedure includes controlled drugs (CD), prescription-only medicines, medicines available over-the-counter (OTC), and illicit drugs. Confirmation of the presence of specific substances will be routinely carried out where amphetamine and opiate class drugs are detected on screening.

SPECIMEN COLLECTION

The appropriate specimen for screening for drugs of abuse is a 'spot' urine sample (20-30 ml) which should be stored in a sterile plastic container without preservative. The patient's full name, hospital or other identification number, and the date and time of collection should be written clearly on the specimen container and on the request form. It is also important to record each client's full home postcode. Special care should be taken to ensure that the specimen obtained is authentic i.e. it has been freshly voided by the patient under supervision, and not subsequently adulterated or substituted for a "drug free" specimen. A urine specimen for drugs of abuse screening should be sent by courier or first class mail, but if there is likely to be a delay in dispatch, it should be kept in a 4^oC refrigerator prior to being sent to the laboratory.

REQUESTS FOR DRUGS OF ABUSE SCREENING

Each urine specimen must be accompanied by an assay request form; this should be completed so as to give all relevant details concerning the patient's identity (including patient's home postcode), date of specimen collection, the drugs suspected of being abused, and all prescribed medication. The daily dose of methadone prescribed for patients on maintenance therapy should also be given. The range of drugs for which it is wished to screen should be stated clearly (see Table 1). Each request must be authorised by a registered medical practitioner. If in doubt about a request - please contact the laboratory +44 (0) 121 507 4135/6.

LABORATORY TECHNIQUES AND QUALITY CONTROL

The Laboratory uses a range of carefully controlled chromatographic and immunoassay techniques for detecting and confirming the presence of drugs of abuse in urine specimens. The Laboratory aims to ensure a minimum of false 'negative' results, and that no false 'positive' results are reported. Confirmatory tests are always performed for the identification of specific amphetamine and opiate class drugs. However, in the cases of benzodiazepines, cannabis, cocaine and methadone, confirmatory tests are NOT routinely carried out, because these immunoassay are relatively specific and rarely produce false positives. Confirmatory test are, however, available for unexpected findings. The Laboratory is able to provide "absolute" confirmation of findings using gas chromatography-mass spectrometry techniques. The Laboratory participates regularly in external quality assurance schemes as part of an effort to achieve a consistently high standard of performance. The "sensitivities" of the urine screening tests currently performed are shown in Table 2.

HOW LONG AFTER USAGE CAN DRUGS BE DETECTED

There is no simple answer to this question, because it depends very much on the substance itself and on other factors such as dosage, frequency of abuse, and individual rates of drug metabolism and excretion; also on the sensitivity of the particular test carried out (Table 2). As an approximate guide, drugs are likely to be detectable in urine within the time scales shown in Table 3.

NOTES ON SOME INDIVIDUAL DRUGS AND DRUG GROUPS

ALCOHOL

Ethyl alcohol (ethanol) is measured by a gas chromatographic procedure which is able to differentiate it from other alcohols, notably methanol and isopropanol. The results of a urine ethanol assay is expressed qualitatively as "positive" or "negative". The quantitative measurement of ethanol in blood (which requires a 4 ml specimen in a fluoride-oxalate container) is the preferred test in chronic alcoholism or in an acutely intoxicated patient. Note that the Laboratory does not undertake the analysis of samples for the purpose of the Road Traffic and Transport Acts.

AMPHETAMINES

Amphetamine (& related compounds)

Abuse of amphetamines particularly amphetamine itself, which is a controlled drug (CD) is relatively common in the West Midlands. The screening tests carried out in this Laboratory are able to distinguish amphetamine from many closely related compounds, some of which are also controlled drugs. Many "over-the-counter" (OTC) medicines contain substances e.g. ephedrine pseudoephedrine and phenylpropanolamine, that are structurally related to amphetamine; hence they can be identified in the "standard" screening procedure. Some other prescribed medicines (POM) that belong to the amphetamine class of drugs such as fenfluramine (POM) and phentermine (CD) can also be identified. In the case of methamphetamine abuse, its metabolite amphetamine may also be detected in urine. The screening tests can also detect a number of 'new' illicit amphetamine-like drugs of abuse: such as methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA, "ecstasy") and methylenedioxyethylamphetamine (MDEA). It should b noted that these screening tests are unable to differentiate between dextro (+) amphetamine (dexamphetamine) and equimolar racemic mixtures of dextro (+) and laevo (-) isomers that are present in "street" amphetamine. However, a test is now available that is able to measure the ratio of (+) and (-) isomers of amphetamine. If this analysis is required the L/D amphetamine isomer test should be requested. Results are expressed as the ratio (percentage) of L/D amphetamine and are interpreted as follows:

L/D Ratio (%) Interpretation

< 20% Subject taking prescribed (d) amphetamine only

20-50% Subject taking prescribed (d) amphetamine and "topping-up" from "street" sources, or using "street" amphetamine but with access to prescribed (d) amphetamine.

> 50% Subject most likely abusing "street" amphetamine only.

BARBITURATES

Barbiturate abuse is now relatively uncommon. Because of their low frequency of detection in addicts, barbiturates are not included as part of the 'routine' screening procedure and will only be screened for if specifically requested. The barbiturate screening procedure is able to detect most of the commonly abused barbiturates.

BENZODIAZEPINES

The abuse of benzodiazepines is relatively common, but the "standard" screening procedure is unable to distinguish between different benzodiazepines. Since a number of benzodiazepines share common pathways of metabolism it is not possible to test for the abuse of specific benzodiazepines e.g. temazepam or diazepam. It is also difficult to detect 'low' dose benzodiazepine abuse. Benzodiazepines are now part of the routine screening procedure (Table 1).

BUPRENORPHINE (TEMGESIC)

There is some evidence for the abuse of buprenorphine (CD) within the UK. It has also been detected in urine samples from a number of drug abusers in the West Midlands. However detection of this drug can only be achieved by using a specific GC-MS procedure. Because of the cost implications, this can be analysed, but an additional charge will be made.

CANNABIS (Cannabinoids, THC)

The use of cannabis is widespread throughout the U.K. but the clinical significance of its detection in urine is uncertain. The primary psychoactive ingredient of cannabis is D⁹-tetrahydrocannabinol (THC), which accumulates in body fat because of its high lipid solubility. The amount stored in body fat is a function of the amount, frequency and potency of cannabis used. THC is slowly released from body stores over time and metabolised by the liver to produce a variety of inactive products (metabolites). The main metabolite is 11-nor-D⁹-carboxy THC (THC-COOH) which is conjugated with glucuronic acid and excreted in urine.

Screening for cannabis metabolites in urine (cannabinoids) is carried out by a specific immunoassay procedure. Such assays detect the presence of several cannabinoid substances in urine. Different assay cut-offs may be employed; most commonly 50 µg/L. The important aspects of these assays are listed in the following table:-

In exceptional cases confirmation of positive results can be carried out by the specific analysis (gas chromatography-mass spectrometry) of the major metabolite of cannabis in urine (THC-COOH). 'Positive' results will be reported for those specimens with a THC-COOH concentration > 15 µg/L. The current Laboratory policy is to only report those samples as being positive for cannabis if above the immunoassay 50 µg/L cut-off. Cannabinoids are part of the routine screening procedure (Table 1).

COCAINE

The use of cocaine (CD) as its hydrochloride salt or the free base form (crack) is reported to be increasingly common. The screening test carried out in this Laboratory is designed to detect the presence of the main cocaine metabolite, benzoylecgonine, in urine. In heavy or chronic users, the presence of unchanged cocaine and the metabolite, ecgonine methyl ester (methylecgonine) may also be detected in urine by the routine chromatographic procedure. The detection of benzoylecgonine is part of the routine screening procedure (Table 1).

DEXTROMORAMIDE (Palfium)

There is some limited abuse of dextromoramide (CD) in the UK, including the West Midlands. Its detection in urine is difficult without the application of a specific liquid chromatographic screening procedure. If there is a clinical indication to detect the presence of this drug in a particular case, the Laboratory must be contacted directly.

DEXTROPROPOXYPHENE

This prescription only analgesic is infrequently abused. However, it can be easily be detected by the chromatographic confirmation procedure. It is commonly detected in urine in patients taking Coproxamol (dextropropoxyphene plus paracetamol) rather than subjects abusing dextropropoxyphene alone (Doloxene).

FENTANYL (Durogesic, Sublimaze)

This synthetic opioid is a controlled drug (CD) but is infrequently abused. It will not normally be detected by the routine opiate screening procedure, however, it may be detected by specific confirmatory techniques.

GHB ("GBH")

Gamma-hydroxybutyrate (GHB), Somsanit, Anetamin is an anaesthetic agent no longer in current clinical use, although available illicitly, which causes drowsiness euphoria, dizziness, visual disturbances, and in large doses, unconsciousness. Peak concentrations are observed within the first 4 hours, following administration/ingestion, but the drug may be undetectable in urine by 12-24 hours. It is not detected by the Laboratory's routine screening procedure. (Please contact the laboratory for further information regarding the testing for GHB).

KETAMINE

Ketamine is a dissociative anaesthetic, and as such, has little abuse potential. However, recently ketamine has been mixed with amphetamine to give an "ecstasy" type response of energetic euphoria. It is possible for the Laboratory to detect ketamine, but only if the specimen is collected soon after ingestion.

KHAT

The main effect of chewing khat leaves is an increase of energy and alertness giving rise to amphetamine-like stimulatory effects. The most important constituent of Khat is the alkaloid Cathinone. It may be possible to detect the metabolites of khat but this has yet to be established since no reported/substantiated cases have yet been submitted to the Laboratory for investigation.

LSD (Lysergic acid diethylamide)

There is some evidence for an increasing abuse of this hallucinogenic drug within the UK. "Dosages" of LSD are extremely small (< 100 µg) and subsequent concentrations in urine are very low (<1 µg/L). (please ask the Laboratory for more advice concerning this screening technique).

METHADONE

The "standard" screening procedure is designed to detect the presence of the primary methadone metabolite (EDDP) in urine. In those subjects where EDDP is detected by the specific initial immunoassay screen, and they are known to be prescribed methadone, no further confirmatory testing will be performed. In those subjects where methadone is not prescribed but EDDP is detected, or those thought to be non-compliant and adding methadone to their urine, specimens will be screened for the presence of both methadone and EDDP. It is therefore important to indicate whether or not methadone is prescribed, or if adulteration of urine specimen by a subject is suspected.

MORPHINE

There is increasing abuse of prescribed morphine (CD) particularly controlled oral preparations such as MST and Oramorph. Abuse of morphine can easily be detected by the routine opiate screening procedure. However, it is not possible to differentiate between morphine resulting from heroin abuse and that from the abuse of morphine containing preparations.

NALBUPHINE (Nubain)

Nalbuphine is a synthetic prescription only (POM) opioid drug that is available as 1 ml ampoules (10 mg/ml) for injection (Nubain). There is growing evidence for the abuse of Nalbuphine, particularly in body builders. The drug will not be detected in the routine opiate immunoassay screening procedure. Because dosages taken are relatively small, it is currently difficult to confirm its presence in urine using specific confirmation procedures. Please check with the Laboratory for the latest information on this drug.

OPIATES

Abuse of heroin (diamorphine) is still widespread, although abuse of other opiates such as codeine and, more recently morphine is also common. The "standard" screening procedure is able to differentiate between the recent usage of the three major opiates - heroin, codeine and dihydrocodeine. Following heroin usage, only morphine is commonly detected in urine; 6-monoacetyl morphine (6-MAM) and codeine may also be detected following relatively recent heroin usage. Following codeine usage, a small amount of morphine as a minor metabolite is commonly observed. Therefore it may be difficult to distinguish between the abuse of heroin-plus-codeine, and the abuse of codeine alone, when 1 or 2 days have elapsed from the time of the ingestion. Following dihydrocodeine usage only dihydrocodeine will be detected. (See Table below). Dihydrocodeine is not converted to morphine. Pholcodine, an opiate antitussive agent in several OTC medicines, is detected by the immunoassay screening procedure, but it is not converted to morphine or codeine and does not interfere with the confirmatory tests carried out to differentiate between the opiates which may be present in urine. Recent ingestion of poppy seeds in the diet may cause problems of interpretation, where large quantities have been taken, since both morphine and codeine may be detected following the consumption of poppy seed containing food products.

Confirmation of initial screening results is routinely performed by gas chromatography-mass spectrometry (GC-MS).

DETECTION OF OPIATE ABUSE

¹ May only be detected following recent heroin use.

² May be detected following poppy seed ingestion.

PENTAZOCINE

This synthetic opioid is a controlled drug (CD) but is infrequently abused. It will not be detected by the routine opiate immunoassay screening procedure. However, if analysis of this drug is requested it can easily be detected by one of the chromatographic confirmation procedures.

PETHIDINE

This synthetic opioid is a controlled drug (CD) but is infrequently abused. It will not be detected by the routine opiate immunoassay screening procedure. However, if analysis of this drug is requested, it can easily be detected by one of the chromatographic confirmatory procedures.

PHENCYCLIDINE ("Angel Dust", PCP)

Currently, there is no evidence for any significant availability or abuse of this drug in the UK. It may be possible to detect the presence of this drug in urine, but this is uncertain. The Laboratory should be contacted directly if this drug is suspected.

TESTS FOR THE DILUTION OF URINE

The Laboratory will determine the creatinine concentration of all urine specimens submitted for screening to detect "abnormally" dilute specimens, i.e. those with creatinine concentrations below 1.8 mmol/L (0.2 g/L).

DRUGS THAT GIVE POSITIVE OPIATE RESULTS

The following table shows drugs that can give rise to positive initial opiate screens.

DRUGS THAT GIVE POSITIVE AMPHETAMINE RESULTS

The following table shows drugs that can give rise to positive initial amphetamine screens.

A SAMPLE REPORT

Reports are currently printed onto A5 paper, with the laboratory address, the destination address and the name of the person authorising the report on the one side. The report itself is printed on the other side, together with any comments. (Click on this link to see a sample report.)

LAXATIVE ABUSE

A range of commonly abused laxatives can be detected in urine. These are bisacodyl, danthron, phenolphthalein and rhein. This assay requires a minimum of 10 ml of urine submitted in a sterile plastic container without a preservative.

VOLATILE-SUBSTANCE-ABUSE (VSA)

The Laboratory is now able to offer a service for the detection of volatile-substance-abuse (aerosol, glue or solvent inhalation). However, the range of substances involved is very wide, and their detection with good sensitivity and specificity can sometimes be difficult, particularly more than 12-24 hrs since abuse. A 10 ml whole blood sample - heparinised or EDTA - is required for this investigation; great care must be taken to avoid gel separator tubes and contamination with exogenous volatile substances. Please contact the Laboratory directly before sending such specimens.

EMPLOYMENT SCREENING

The Laboratory is able to screen urine specimens as part of pre-employment or employment screening for drug and substance abuse. These should be submitted through a registered medical practitioner or occupational health department. It should be noted that it is advisable to have an established workplace drugs policy to cope with any positive results that may be detected. All such requests should be discussed with the Laboratory prior to dispatch. Separate guidelines and chain-of-custody forms are available from the Laboratory.

CHAIN OF CUSTODY

Chain of Custody is a legal term that refers to the ability to guarantee the identity and integrity of the specimen from collection through to reporting of the test results. 

It is a process used to maintain and document the chronological history of the specimen. (Documents should include name or initials of the individual collecting the specimen, each person or entity subsequently having custody of it, the date the specimen was collected or transferred, employer or agency, specimen number, patient's or employee's name, and a brief description of the specimen.)

 A secure chain of custody, together with the analytical techniques used by the Regional Laboratory for Toxicology to confirm the identity of drugs present in a specimen, leads to the production of a legally defensible report.

CUMULATIVE REPORTS

These are available on individual patients and on a yearly basis to clinics upon written request. There may be a charge levied for this service, please contact the laboratory.

CHARGES

The scale of charges is available from the laboratory on request.

REQUEST FORMS

Request forms for drugs of abuse screening are available from the Departmental Secretary (+44 (0) 121 507 4135). Specimen collection bottles are not normally provided but can be provided (on a short-term basis) for clinics who have difficulty in obtaining appropriate specimen containers.

CONCLUDING REMARK

These guidelines reflect the Laboratory's experience, over many years, in the investigation of patients in the West Midlands with drug problems. The pattern of abuse changes from time to time, and a few patients may abuse unusual or exotic drugs. The Laboratory staff will do their best to offer advice or help in circumstances which are not covered by these notes. The Laboratory welcomes visits from drug clinic staff, additionally Senior Laboratory staff are willing to participate in teaching sessions at clinics. For more information, please contact (see below):

CONTACT POINTS

Dr. S.A. George, Principal Clinical Scientist, Section Head, 'phone +44 (0) 121 507 6029

Mrs C George, Senior Clinical Scientist, 'phone +44 (0) 121 507 6027

Dr. R.A. Braithwaite, Head of Department, 'phone +44 (0) 121 507 4134

FAX number of Laboratory office: +44 (0) 121 507 6021

Table 1. DRUGS SCREENED FOR IN THE ROUTINE URINE

DRUG ABUSE SCREENING REQUEST

1.     Standard Immunoassay Screen (All specimens)

Amphetamines *

Benzodiazepines

Cocaine (metabolite)

Cannabinoid (50 µg/L cut-off)

Methadone metabolite (EDDP)

Opiates *

Urine Creatinine

* Additional confirmation tests performed on all "positive" tests at no extra charge.

 

2.     Additional Substances Screened for by Specific Request at no extra charge

Alcohol

Barbiturates

Ecstasy (MDMA) and related drugs (MDA, MDEA)

3.     Additional Substances Screened for by Specific Request for which an additional charge
        will  be levied.

Amphetamines will be confirmed by GC, opiates by GC-MS. Additional confirmatory tests will be carried out by GC-MS for "positive" occupational screening tests (cannabis, cocaine, benzodiazepines, methadone).

Table 2. SENSITIVITIES OF URINE SCREENING

AND CONFIRMATION TESTS FOR DRUGS OF ABUSE

At concentrations below the limit of detection, the drug (or metabolite) will not normally be detected by the usual screening procedure. A result reported as 'positive' in a screening test implies that the concentration of drug present is in excess of the limit given here. Note that the sensitivity of drug detection will be reduced in dilute urine specimens.

The action limits used by the laboratory for employment and pre-employment confirmatory tests cited above are the same as those used by most other UK laboratories performing drugs of abuse screening, and conform to the Substance Abuse and Mental Health Services Administration (SAMHSA) guidelines. In addition, the EU and / or UK guidelines can be applied to screening and confirmatory tests performed. Please contact the laboratory for further information.

Table 3. APPROXIMATE DETECTION TIMES OF SOME COMMON

DRUGS OF ABUSE IN URINE*

• Note that detection times are only very approximate and are very dependent upon the dose, its frequency, route of administration and urine excretion/dilution.

Last modified: July 27, 2007

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Copyright ^© [Regional Laboratory for Toxicology], 2002. All rights reserved.