Immunoassays for Drug Screening in Urine: Chances, Challenges, and Pitfalls

Abstract

Immunoassays are presently used worldwide for the rapid screening of drugs. Despite the fact that they are a highly valuable tool for the testing of legal and illicit drugs, there is a real risk of false-positive and false-negative findings and many pitfalls must be taken into account when these tests are used in an uncritical manner and without valid confirmation procedures. In a long-standing successful cooperation with a large psychiatric hospital, we checked doubtful and nonplausible immunochemical findings in urine with gas chromatography-mass spectrometry (GC-MS) confirmation methods. The reported case histories demonstrate typical pitfalls, for example, influence of changing nutritional habits, use of sweeteners (cyclamate), uncritical creatinine correction, impaired elimination, or cross-reactivities of simultaneous therapeutic medication. In accordance with national and international associations, immunoassays are recommended as a useful tool for screening. However, confirmation analysis with conclusive methods (GC-MS or liquid chromatography-MS) is unavoidable for valid substance identification, discrimination between active and inactive metabolites, detection of congeners, and accurate determination of concentrations in body fluids.

Time-dependent postmortem redistribution of butyrfentanyl and its metabolites in blood and alternative matrices in a case of butyrfentanyl intoxication

“…These findings could be further confirmed by manual evaluation of LC-Ion Trap data files and finally proven by comparison to a commercially available reference standard. The positive immunoassay result on LSD can probably be explained by cross reactivity with butyrfentanyl, as cross reactivity with fentanyl is already well known [31]. Missing competing causes of death (both toxicological and medicinal) lead to the conclusion, that an intoxication with butyrfentanyl was most probably the cause of death; thus, representing the first report on fatal butyrfentanyl monointoxication.…”

Development and validation of an ultra‐fast and sensitive microflow liquid chromatography‐tandem mass spectrometry (MFLC‐MS/MS) method for quantification of LSD and its metabolites in plasma and application to a controlled LSD administration study in humans

“…Immunoassay prescreens are typically performed in clinical and forensic toxicology to allow for fast differentiation between negative and positive presumptive tests. However, in terms of LSD, major cross‐reactivity is known through fentanyl or different fentanyl‐analogues . Application of fentanyl is common as an initial emergency treatment, especially following traffic accidents.…”

“…However, in terms of LSD, major cross-reactivity is known through fentanyl or different fentanylanalogues. [18] Application of fentanyl is common as an initial emergency treatment, especially following traffic accidents. Consequently, high numbers of false-positive LSD immunoassays routinely occur.…”

Current Status of Point-of-Care Testing in Clinical Toxicology

“…32 However, the use of abuse chromatographic techniques such as gas chromatography mass spectrometry and liquid chromatography-mass spectrometry for screening of drugs of is gaining more interest. 33 Usually, laboratory-based analysis is time-consuming because it involves multiple steps.…”