Trends using biological target-based assays for drug detection in complex sample matrices
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TRENDS
Trends using biological target-based assays for drug detection in complex sample matrices Michael F. Santillo 1 Received: 20 March 2020 / Revised: 15 April 2020 / Accepted: 23 April 2020 # This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020
Abstract In vivo, drug molecules interact with their biological targets (e.g., enzymes, receptors, ion channels, transporters), thereby eliciting therapeutic effects. Assays that measure the interaction between drugs and bio-targets may be used as drug biosensors, which are capable of broadly detecting entire drug classes without prior knowledge of their chemical structure. This Trends article covers recent developments in bio-target-based screening assays for detecting drugs associated with the following areas: illicit products marketed as dietary supplements, food-producing animals, and bodily fluids. General challenges and considerations associated with using bio-target assays are also presented. Finally, future applications of these assays for drug detection are suggested based upon current needs. Keywords Bioassays . Biosensors . Drug monitoring/drug screening . Enzymes . Pharmaceuticals . Receptors/ion channels
Introduction A drug’s mechanism of action is based upon its interaction with its biological targets (bio-targets) such as enzymes, receptors, ion channels, and transporters [1]. Binding to biotargets has an impact on physiological processes, which, in turn, leads to therapeutic or other outcomes. Assays that measure the interaction between drugs and bio-targets are performed in vitro using whole cells or cellular lysates containing isolated bio-targets [2–4]. In the fields of pharmacology and toxicology research, bio-target assays play a key role in discovering new drugs and understanding how these drugs alter physiological function, which contributes to drug safety [5] and efficacy [6]. While bio-target assays are mainstays of pharmacology and toxicology research, they can also be employed as analytical Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00216-020-02681-x) contains supplementary material, which is available to authorized users. * Michael F. Santillo [email protected] 1
Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration (FDA), 8301 Muirkirk Rd, Laurel, MD 20708, USA
methods, serving as drug biosensors. They are useful for detecting drugs in a variety of matrices, especially those related to dietary supplements, food-producing animals, and bodily fluids (e.g., doping, recreational drug abuse). Additionally, they can detect multiple drugs within a drug class, which often possess dissimilar chemical structures but bind to a common bio-target. Bio-target assays also have the capacity to detect novel drug analogues, which are often encountered in illicit cases. The ability to detect structurally diverse and emerging dr
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