This is a contrast to older drug classes (e.g., barbiturates, benzodiazepines, and TCAs), where there is significant structural similarity between all drugs within the class. The clinical implication of this is that it would be difficult to design an ‘SSRI overdose screen’ or ‘atypical antipsychotic overdose screen’ with standard immunoassay technology. It also suggests that development of DOA/Tox Afatinib mouse immunoassays has not kept pace with the development of new drugs relevant to the ED community or with changes in patterns of abuse of illicit and

prescription drugs. The analytical methods currently used mainly for DOA/Tox confirmatory testing, such as GC/MS and liquid chromatography/tandem mass spectrometry Inhibitors,research,lifescience,medical (LC/MS/MS), can specifically identify (and in some cases quantitate) drugs and their metabolites. This technology, however, is technically demanding, labor-intensive, expensive compared to immunoassays, and usually available only at reference laboratories Inhibitors,research,lifescience,medical or in clinical laboratories associated with larger medical centers [7]. A future goal would be to develop and adapt GC/MS, LC/MS/MS, or a novel technology in a manner to be more widely Inhibitors,research,lifescience,medical accessible clinically, so as to provide detailed drug exposure data with a rapid turnaround time, allowing ED physicians

to make more specific diagnoses and treatment plans. A scientifically similar challenge is in emerging technology to develop portable yet analytically robust sensors for chemical warfare agents or environmental Inhibitors,research,lifescience,medical pollutants [72], and there may be opportunities to develop clinical applications using related technology. An important limitation of the 2D similarity approach used in our study is that this cannot account for the complex

three-dimensional (3D) molecular interactions that mediate antibody-antigen binding as occurs in immunoassays. To our knowledge, a 3D structure of an antibody used in a marketed DOA/Tox screening immunoassay bound to Inhibitors,research,lifescience,medical its antigenic target has not been reported, although there has been structural determination of several other antibodies being evaluated as novel antidotes to DOA overdose (e.g., PCP [73] and cocaine [74,75]), in which the antibody interacts with all portions of the target molecule. For DOA/Tox screening immunoassays where similar antibody-drug interactions apply, whole molecule similarity measures (as used in our study) seem appropriate for prediction; however, this may not always be the case. A crystal structure of morphine Non-specific serine/threonine protein kinase bound to a monoclonal antibody showed that the antibody interacted with the more hydrophobic portion of morphine, while the hydrophilic half was mostly solvent exposed [76]. For target compounds like morphine, similarity searching using substructures may therefore be worth evaluating, although depending on the size of the molecule, complexity, and novelty this may yield many more molecules predicted as positives.