Standard Article

Drugs of Abuse, Analysis of

Clinical Chemistry

  1. Amitava Dasgupta

Published Online: 20 SEP 2013

DOI: 10.1002/9780470027318.a0511.pub2

Encyclopedia of Analytical Chemistry

Encyclopedia of Analytical Chemistry

How to Cite

Dasgupta, A. 2013. Drugs of Abuse, Analysis of. Encyclopedia of Analytical Chemistry. 1–27.

Author Information

  1. University of Texas-Houston Medical School, Houston, TX, USA

  1. Update based on the original article by Amitava Dasgupta, Encyclopedia of Analytical Chemistry, © 2000, John Wiley & Sons, Ltd.

Publication History

  1. Published Online: 20 SEP 2013


Alcohol is the most widely abused legal drug in USA. Other widely abused illegal drugs are amphetamines, cocaine, cannabinoids, opiates, barbiturates, benzodiazepines, methadone, methaqualone, and phencyclidine (PCP). Lysergic acid diethylamide (LSD), a popular drug in 1960, is coming back in the illegal market. Drug testing in USA is either for medical or legal purpose, and urine is the preferred specimen for both testing procedures. However, blood and gastric contents are useful in detecting drugs in the case of an acute, recent overdose. Alcohol levels in blood can be measured by either immunoassay or gas chromatography (GC), although many hospital laboratories use immunoassay for measuring blood alcohol because it is technically simple. False-positive alcohol concentration in immunoassays may result from high concentrations of lactate dehydrogenase (LDH) (lactic acidosis) and lactate in a specimen. However, this interference can be eliminated by measuring the alcohol concentration in the protein-free ultrafiltrate. Screening of abused drugs by immunoassay also has certain limitations. For example, several over-the-counter cold medications contain ephedrine or pseudoephedrine that can cause positive results in amphetamine immunoassays because of their structural similarity to methamphetamine. Therefore, immunoassay screening tests provide only preliminary results. People try to beat drug testing by adding a variety of compounds such as salt, lemon juice, household bleach, and Visine eye drops to their urine during legal drug testing, which may invalidate immunoassay results. Therefore it is important to check sample integrity (temperature, pH, specific gravity). In addition, Internet-based adulterants such as nitrite, pyridinium chlorochromate (PCC), glutaraldehyde, and stealth can also invalidate drug testing, but their presence cannot be detected by specimen integrity testing and special tests are needed for their detection. True positive results from the ingestion of poppy seed cake (contains opiates), health Inca tea (contains cocaine), or hemp seed oil (contains tetrahydrocannabinol (THC)) in drug testing have been reported. Confirmation of the abused drug is essential to follow up screening tests and should be done using a different analytical technique. Gas chromatography/mass spectrometry (GC/MS) is considered the gold standard for the confirmation of abused drugs in biological fluids and tissue specimens. The preanalytical steps include extraction of the drug from urine or serum matrix using an organic solvent followed by derivatization. The common derivatizing agents are trifluoroacetic anhydride, pentafluoropropionic anhydride, heptafluorobutyric anhydride, methanolic sulfuric acid, N-O-bis(trimethylsilyl) trifluoroacetamide, and so on. New derivatization techniques have appeared in the literature for GC/MS confirmation of abused drugs. The perfluorooctanoyl and 4-carbethoxyhexafluorobutyryl derivatives of amphetamines are less volatile than traditional fluoro derivatives, have higher molecular weights, and are more useful for unambiguous identification. Propyl chloroformate and very recently 2,2,2-trichloroethyl chloroformate have been introduced as new derivatization reagents for amphetamines. Another challenge in testing drugs of abuse is the identification of designer drugs because immunoassay screening test may not be able to detect the presence of a designer drug in the urine specimen. γ-hydroxybutyric acid (GHB) has been reported as a date rape drug that can only be identified in blood and urine using high-performance liquid chromatography/mass spectrometry (HPLC/MS). Hair analysis is becoming popular owing to the long-term deposition of many abused drugs in hair. However, the analytical challenges are greater as the concentrations are low, which poses an additional analytical challenge.