Journal article
Cross-reactivity studies and predictive modeling of "Bath Salts" and other amphetamine-type stimulants with amphetamine screening immunoassays
Clinical toxicology (Philadelphia, Pa.), Vol.51(2), pp.83-91
02/01/2013
DOI: 10.3109/15563650.2013.768344
PMID: 23387345
Abstract
Introduction. The increasing abuse of amphetamine-like compounds presents a challenge for clinicians and clinical laboratories. Although these compounds may be identified by mass spectrometry-based assays, most clinical laboratories use amphetamine immunoassays that have unknown cross-reactivity with novel amphetamine-like drugs. To date, there has been a little systematic study of amphetamine immunoassay cross-reactivity with structurally diverse amphetamine-like drugs or of computational tools to predict cross-reactivity. Methods. Cross-reactivities of 42 amphetamines and amphetamine-like drugs with three amphetamines screening immunoassays (AxSYM
®
Amphetamine/Methamphetamine II, CEDIA
®
amphetamine/Ecstasy, and EMIT
®
II Plus Amphetamines) were determined. Two- and three-dimensional molecular similarity and modeling approaches were evaluated for the ability to predict cross-reactivity using receiver-operator characteristic curve analysis. Results: Overall, 34%-46% of the drugs tested positive on the immunoassay screens using a concentration of 20,000 ng/mL. The three immunoassays showed differential detection of the various classes of amphetamine-like drugs. Only the CEDIA assay detected piperazines well, while only the EMIT assay cross-reacted with the 2C class. All three immunoassays detected 4-substituted amphetamines. For the AxSYM and EMIT assays, two-dimensional molecular similarity methods that combined similarity to amphetamine/methamphetamine and 3,4-methylenedioxymethampetamine most accurately predicted cross-reactivity. For the CEDIA assay, three-dimensional pharmacophore methods performed best in predicting cross-reactivity. Using the best performing models, cross-reactivities of an additional 261 amphetamine-like compounds were predicted. Conclusions. Existing amphetamines immunoassays unevenly detect amphetamine-like drugs, particularly in the 2C, piperazine, and β-keto classes. Computational similarity methods perform well in predicting cross-reactivity and can help prioritize testing of additional compounds in the future.
Details
- Title: Subtitle
- Cross-reactivity studies and predictive modeling of "Bath Salts" and other amphetamine-type stimulants with amphetamine screening immunoassays
- Creators
- M Petrie - The Permanente Medical Group Regional LaboratoriesK. L Lynch - Department of Laboratory Medicine, University of California San FranciscoS Ekins - Collaborations in ChemistryJ. S Chang - The Permanente Medical Group Regional LaboratoriesR. J Goetz - Children's Hospital Medical CenterA. H. B Wu - Department of Laboratory Medicine, University of California San FranciscoM. D Krasowski - Department of Pathology, University of Iowa Hospitals and Clinics
- Resource Type
- Journal article
- Publication Details
- Clinical toxicology (Philadelphia, Pa.), Vol.51(2), pp.83-91
- Publisher
- Taylor & Francis
- DOI
- 10.3109/15563650.2013.768344
- PMID
- 23387345
- ISSN
- 1556-3650
- eISSN
- 1556-9519
- Language
- English
- Date published
- 02/01/2013
- Academic Unit
- Pathology
- Record Identifier
- 9984046934002771
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