J Clin Pathol 1999;52:713–718 713 Leader J Clin Pathol: first published as 10.1136/jcp.52.10.713 on 1 October 1999. Downloaded from Detection of drug misuse—an addictive challenge. John H Galloway, Ian D Marsh Abstract base: “crack”). In addition to these illicit It is now accepted that drug misuse is a compounds various drugs intended for medical large and growing problem in the United use have been “adopted” into misuse. In Kingdom, some estimates of the number particular the benzodiazepines (diazepam and of regular illicit drug users being as high temazepam) are widely misused, as are opiates as three million. The aim of this paper is including diamorphine (heroin) and dihydroco- to provide insight into the methods used to deine. Ketamine, methadone, tricyclic antide- detect drug misuse. The strategy adopted pressants, and dextropropoxyphene are further by one laboratory is described and meth- examples of prescribed drugs encountered in ods of screening for, and identification of, individuals who have not been prescribed them. a wide range of compounds are provided. The casual use of these drugs may never be a No claim is made that this is the best problem and is, for many, a natural part of rec- approach or that the list of drugs detected reational activity. The use of these drugs is comprehensive; the range of drugs becomes a problem only if the individual encountered is always increasing and the involved becomes a habitual user and suVers lists are constantly updated. It is hoped longer term physical problems (illness and that users of toxicology laboratory serv- infections) and psychological problems which ices will gain an appreciation of the capa- make them unable to be fully active and bilities and limitations of the techniques productive members of society. available; and that those who may wish to The statistics of drug addicts notified to the provide such a service will find the neces- United Kingdom Home OYce (London: Gov- sary information in a readily accessible ernment Statistical Service) give some evi- format. dence of the continued growth in the use of http://jcp.bmj.com/ ( 1999; :713–718) J Clin Pathol 52 drugs of abuse (at a rate greater than 10% per Keywords: drug misuse; laboratory analytical annum) as measured by the number of addicts techniques; screening notified to the Home OYce and by the number of drug seizures. The statistics for numbers of The only way to establish the limits of what is abusers only include those seeking help from possible is to test the boundaries of the impossi- statutory bodies and give no indication of the ble. overall number of users. A more meaningful indication of the scale of the problem comes on September 28, 2021 by guest. Protected copyright. Why look for drugs of abuse? from calculations made by Atha and Blanchard For hundreds, indeed thousands of years, the (in preparation for publication) to be found on use of chemicals for recreational or religious the internet site of the Institute for the Study of purposes has been part of most cultures. Even Drug Dependence (http://www.isdd.co.uk): in Victorian Britain, laudanum and opium the estimated number of regular drug users in were used by respectable members of society, the United Kingdom has increased from and cocaine was readily available in prepara- approximately 1 million in 1982/84 to 2.5–3 tions such as Vin Mariani and the original million in 1995. Coca-Cola. More widely within Western soci- Drug abuse has eVects not only on the user ety, the use of alcohol and nicotine as an aid to but on the whole of society. This can take the relaxation and social discourse has been gener- form of crime related to the acquisition of ally accepted, apart from the abortive attempt drugs, and danger to other members of society Department of Clinical by the government of the USA to impose pro- resulting from the modification of the behav- Chemistry, Royal hibition of alcohol through the Eighteenth iour of drug users, who may become dangerous Hallamshire Hospital, Amendment to the Constitution in the first half or irresponsible. Drug abuse will also cause an Glossop Road, of this century. increased risk of the spread of transmittable SheYeld S10 2JF, UK J H Galloway Ever since the early days of a modern youth diseases not only between addicts but also into I D Marsh culture in the late 1950s and early 1960s the use associated populations. of stronger drugs for recreation has been The circumstances in which screening for Correspondence to: developed. These chemicals include illicit prepa- drugs of abuse may be required are diverse. A Dr Galloway. rations such as heroin, Ecstasy (3,4-methy- request may be made by casualty departments Accepted for publication lenedioxy-N-methylamphetamine, MDMA), simply to exclude the presence of drugs in a 14 May 1999 and cocaine (as the hydrochloride, or as free patient who has been admitted unconscious, 714 Galloway, Marsh with a decreased level of consciousness, or dis- ment screening or clinic situation should be J Clin Pathol: first published as 10.1136/jcp.52.10.713 on 1 October 1999. Downloaded from playing bizarre behaviour. In most situations made aware that sample substitution by drug the demonstration of the presence of a drug misusers (the use of a more “appropriate” which the patient should not be taking is suY- urine sample from the clients/patients point of cient. However, in a minority of cases it may be view) is relatively common. necessary to perform quantification in order to Some liaison with the members of staV establish the degree of clinical eVect of the drug involved in obtaining the sample can be desir- and this will present a problem which must be able, especially as they can often be junior considered by any potential service providers. medical staV faced with a possible drug addict Clinics oVering support and advice to drug for the first time. In addition, because a screen addicts are widespread and include drug for drugs is open ended (it is never possible to dependency units, community drug teams, and prove the absence of all drugs) it is useful to be outreach services. These require regular drug given a clear indication as to whether the pres- checks on their clients in order to establish ence of any particular substance or group of appropriate further treatment and they provide substances is suspected. the most significant demands for the routine toxicology laboratory. The initial screen Finally, though rarely encountered in the Commercially prepared immunoassay systems past, screening for drugs of abuse is now are now widely available for initial screening of increasingly performed both as a prerequisite urine samples. These include EMIT (the before employment and randomly during enzyme multiplied immunoassay technique), employment. for instance the Dade-Behring system (Walton In all of the situations outlined above some Manor, Milton Keynes, UK), FPIA (fluores- control of sample integrity is desirable, but in cent polarisation immunoassay) oVered by the case of employment screening it is impera- Abbott (Maidenhead, UK), and chemilumi- tive, as the consequences of an incorrect result nescence oVered by DPC (Immulite) (DPC, have far reaching consequences. Chain of cus- Llanberis, UK). A simple though expensive tody documentation must be used and the “dipstick” system supplied by Roche (Welwyn samples (in duplicate, one to be tested and one Garden City, UK), “Ontrak”, uses the princi- to remain sealed to be used in the event of a ple of microparticle capture inhibition to problem—usually a challenged positive find- provide a screen for use within clinics, and the ing) must be in tamper proof containers. introduction of similar systems for roadside testing (using samples of perspiration) has What sample to use? been proposed. The microparticle capture If we were interested in monitoring therapeutic inhibition system is also available in a more drugs we would, in most cases, wish to monitor economical version for use within the labora- concentrations present in the blood of the tory (Roche Cobas/Integra). patient and relate the results to established The instrumentation that may be used therapeutic windows. However, in cases of ranges from simple dedicated machines, such http://jcp.bmj.com/ drug misuse our interest is primarily in as the Dade-Behring ETS, to more generally establishing their presence and identity, and used machines, such as Olympus or Roche analysis of blood is not generally used. analysers. In very acute cases, vomitus or stomach Our experience has been with the Dade- washings may be useful if there is evidence that Behring EMIT system using the ETS dedi- the drug has been taken orally. In some cated system; therefore the following descrip- tion is based upon our experience with this. situations sweat may be screened for drugs of on September 28, 2021 by guest. Protected copyright. abuse (as is proposed in the case of roadside Our initial screen is for a panel consisting of testing by the police) but limitations in the opiates, methadone, amphetamines, barbitu- amount of sample available for further proce- rates, benzodiazepines, cocaine metabolite, and dures restrict the value of this approach. There cannabinoids. The ETS is simply calibrated are also published methods for hair analysis, using calibration standards provided at three particularly where a longer term assessment of levels: negative, cut oV, and high. Samples drug use is desired; such analyses are, in our which display activity below the cut oV are des- experience, diYcult and outside the remit of a ignated negative and those that display activity routine laboratory. above the cut oV are designated positive. The Drugs are usually recognised by the body as concentration of drug which is used as the cut being foreign and not capable of being utilised, oV level has been selected to provide optimal and are rapidly processed for excretion.