Drugs of abuse: a challenging landscape for laboratories.
The rapidly growing problem of so-called designer drugs, developed by modifying the chemical structure of existing drugs or the synthesis of new drugs, means that traditional drug detection methods are becoming increasingly inadequate. There is a clear need for adaptable testing solutions which can cope with the evolving picture. Drugs-of- abuse screening technology which allows multiple substances to be detected simultaneously from a single sample offers a good solution and is proving to be groundbreaking for toxicology laboratories.
A moving target
New variations of psychoactive substances are continuously introduced to satisfy (or create) changing appetites. Here is a snapshot of common drugs of abuse today:
MDMA (Ecstasy) is an amphetamine derivative and a common recreational drug. Toxic effects include anxiety, depression, tachycardia, elevated blood pressure, cardiac arrhythmias, pupil dilation, and sleep disorders. Deaths associated with Ecstasy have been reported, often as a result of hyperpyrexia brought on by high levels of exertion, high ambient temperatures, and inadequate fluid intake.
Synthetic cannabinoids are one of the most prevalent and quickly evolving of the designer drugs. Initially developed as therapeutic agents to mimic the effects of cannabis, the unwanted psychoactive properties make these compounds extremely toxic--up to 700 times more potent than THC. These compounds are manufactured to avoid drug laws and are widely available through the internet. When one synthetic cannabinoid becomes a controlled substance, a slight structural modification is made to produce a new synthetic cannabinoid to evade legislation. Initial batches contained compounds such JWHO 18 and AM2201; however, the latest wave of synthetic cannabinoids on the market include UR144/XLR11 and AB PINACA.
Synthetic cathinones, often considered "legal highs," are stimulants that mimic the effect of amphetamines, cocaine, and Ecstasy. Sold as "bath salts" or "plant food," they are labelled "not for human consumption" to circumvent legislation. The majority of these designer drugs are derived from the parent compound cathinone, the active ingredient of the plant khat (Catha edulis).
Piperazine designer drugs--"party pills"--are synthetic chemical compounds. These drugs have a market reputation of being safe, but various studies have reported a significant risk for users. (1)
NBOME, one of the newest psychoactive substances on the market, is a synthetic derivative of phenethylamine with stimulant and hallucinogenic properties. It is often counterfeited as LSD or sold as a "legal" LSD alternative. Reports in the literature detail fatalities as a result of suicides resulting from intense hallucinations. (2)
A two-part process
The analysis of a biological sample for drugs of abuse is a two-tiered process. A laboratory must conduct an initial test (screening test), followed by a confirmatory test on the sample before the specimen can be reported as positive.
The application of immunoassays as a preliminary test to screen for drugs of abuse allows samples to be tested for the presence of drug or drug metabolites in various sample types. Immunoassay tests are based on the antibody-antigen reaction, which provides a relatively fast and straightforward way of determining if drug metabolites are present in the sample. New immunoassay technology is capable of detecting multiple substances at one time from a range of sample types.
If initial screening tests produce positive results, a confirmatory test on the sample is required. This involves more labor- and resource-intensive confirmatory testing methods such as High Performance Liquid Chromatography (HPLC), Liquid Chromatography Mass Spectrometry (LC-MS) and Gas Chromatography Mass Spectrometry (GC-MS). It is thus important that the results produced in initial screening be reliable.
Modern automated immunological technologies advance screening procedures by providing accurate results at high speeds. Lab-on-a-chip technologies have been developed to consolidate a number of tests onto miniature chips. These multiplex immunoassays, based on ELISA principles, can detect multiple drugs of abuse from one undivided patient sample, leading to more time- and labor-effective screening.
A range of sample types
The ability to deal with a range of sample types is vital. Sample types include blood, urine, hair, oral fluid, vitreous humour, forensic samples, meconium, tissue samples, and even mother's milk.
Offering testing on multiple sample types is helpful where there is a risk of sample adulteration. For example, the collection of a urine sample involves the individual producing the sample in the privacy of the toilet. This offers the individual the opportunity to tamper with the sample. However if oral samples can be tested instead, a clinician can take the swab and submit for testing with no possibility of adulteration.
Drug residues remain in certain sample types longer than in others; e.g., some drugs will be undetectable in urine 24 hours after consumption, whereas hair samples retain some drug residues for up to three months after consumption. Hair samples are also less invasive to obtain.
An advanced solution
Today, the technology is routinely available for laboratories to cost-effectively screen a range of biological samples for drugs of abuse. Multiplexing methods set a new standard in immunoassay testing with greater sensitivity and broader detection for drug screening. Lab-on-a-chip methods offer a high throughput multiplex capability that cannot be matched by traditional methods.
As designer drugs and new variations of drugs continue to enter the market, clinical laboratories need to broaden their test menus to keep up. As new sample matrices continue to be explored, multi-matrix platforms will further advance laboratory testing capabilities. Fully automated multiplex methods, offering highly accurate and rapid drug testing in a range of test settings, are likely to gain in acceptance.
(1.) European monitoring center for drug and drug additction. BZP and other piperazines. http://www.emcdda.europa.eu/publications/drug-profiles/bzp.AccesseA December 4, 2014.
(2.) Advisory Council on the Misuse of Drugs (ACMD). NBOMe Compounds: A Review of the Evidence of Use and Harm. Letter to the Home Secretary, https://www.gov. uk/government/uploads/system/uploads/attachment_data/file/261786/NBOMe_ compounds_report.pdf. Accessed December 4,2014.
By Joanne Darragh, PhD, BSc
Joanne Darragh, PhD, BSc, serves as Development Manager, Forensics Toxicology, for Randox Laboratories.
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|Title Annotation:||Special feature: Drugs of abuse|
|Publication:||Medical Laboratory Observer|
|Date:||Jan 1, 2015|
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