As the number of prescriptions, over-the-counter medications and drugs of abuse continue to increase, forensic laboratories are faced with the challenge of developing more comprehensive screening methods in order to detect them in whole blood samples. Another challenge faced by forensic laboratories is detecting and identifying novel synthetic compounds as they emerge and change. Traditional drug screening methods include enzyme immunoassay (EIA) and either gas or liquid chromatography paired with mass spectrometry (GC–MS or LC–MS-MS, respectively). While these methods are good, they have their disadvantages. For example, EIA requires special reagents for each drug class, GC–MS requires extensive sample preparation, and LC–MS-MS only detects drugs on a known inclusion lists of compounds of interest. Described below is the development of a robust and comprehensive screening method for drugs in whole blood samples that eliminates the aforementioned disadvantages of the traditional methods. Using a Q Exactive Focus ™ liquid chromatography-high resolution-accurate mass spectrometer (LC–HRMS-MS), a method was developed that is capable of detecting approximately 200 drugs at a concentration of 2 μg/L for most analytes. This method also employs a more automated data processing feature which reduces processing time. Finally, it has the added benefit of retroactive data analysis, which allows it to be used for unknown drug analysis as well. Used as an initial screening method, the comprehensive drug screen using LC–HRMS-MS has the potential to take on two of the most important challenges faced by forensic laboratories today.

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