Journal article
Chemoinformatic methods for predicting interference in drug of abuse/toxicology immunoassays
Clinical chemistry (Baltimore, Md.), Vol.55(6), pp.1203-1213
06/2009
DOI: 10.1373/clinchem.2008.118638
PMCID: PMC2855823
PMID: 19342505
Abstract
Immunoassays used for routine drug of abuse (DOA) and toxicology screening may be limited by cross-reacting compounds able to bind to the antibodies in a manner similar to the target molecule(s). To date, there has been little systematic investigation using computational tools to predict cross-reactive compounds.
Commonly used molecular similarity methods enabled calculation of structural similarity for a wide range of compounds (prescription and over-the-counter medications, illicit drugs, and clinically significant metabolites) to the target molecules of DOA/toxicology screening assays. We used various molecular descriptors (MDL public keys, functional class fingerprints, and pharmacophore fingerprints) and the Tanimoto similarity coefficient. These data were then compared with cross-reactivity data in the package inserts of immunoassays marketed for in vitro diagnostic use. Previously untested compounds that were predicted to have a high probability of cross-reactivity were tested.
Molecular similarity calculated using MDL public keys and the Tanimoto similarity coefficient showed a strong and statistically significant separation between cross-reactive and non-cross-reactive compounds. This result was validated experimentally by discovery of additional cross-reactive compounds based on computational predictions.
The computational methods employed are amenable toward rapid screening of databases of drugs, metabolites, and endogenous molecules and may be useful for identifying cross-reactive molecules that would be otherwise unsuspected. These methods may also have value in focusing cross-reactivity testing on compounds with high similarity to the target molecule(s) and limiting testing of compounds with low similarity and very low probability of cross-reacting with the assay.
Details
- Title: Subtitle
- Chemoinformatic methods for predicting interference in drug of abuse/toxicology immunoassays
- Creators
- Matthew D Krasowski - Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261, USA. mdk24@pitt.eduMohamed G SiamManisha IyerAnthony F PizonSpiros GiannoutsosSean Ekins
- Resource Type
- Journal article
- Publication Details
- Clinical chemistry (Baltimore, Md.), Vol.55(6), pp.1203-1213
- DOI
- 10.1373/clinchem.2008.118638
- PMID
- 19342505
- PMCID
- PMC2855823
- NLM abbreviation
- Clin Chem
- ISSN
- 0009-9147
- eISSN
- 1530-8561
- Publisher
- England
- Grant note
- K08 GM074238 / NIGMS NIH HHS K08 GM074238-04 / NIGMS NIH HHS K08 GM074238-03 / NIGMS NIH HHS K08-GM074238 / NIGMS NIH HHS
- Language
- English
- Date published
- 06/2009
- Academic Unit
- Pathology
- Record Identifier
- 9984047778502771
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