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A high\u2010throughput ultra\u2010high\u2010performance liquid chromatography\u2010tandem mass spectrometry method for determination of 21 drugs in OF using fully automated 96\u2010well plate supported liquid extraction for sample preparation is presented. The method contains a selection of classic drugs of abuse, including amphetamines, cocaine, cannabis, opioids, and benzodiazepines. The method was fully validated for 200\u2009\u03bcL OF\/buffer mix using an Intercept OF sampling kit; validation included linearity, sensitivity, precision, accuracy, extraction recovery, matrix effects, stability, and carry\u2010over. Inter\u2010assay precision (RSD) and accuracy (relative error) were &lt;15% and 13 to 5%, respectively, for all compounds at concentrations equal to or higher than the lower limit of quantification. Extraction recoveries were between 58 and 76% (RSD\u2009&lt;\u20098%), except for tetrahydrocannabinol and three 7\u2010amino benzodiazepine metabolites with recoveries between 23 and 33% (RSD between 51 and 52 % and 11 and 25%, respectively). Ion enhancement or ion suppression effects were observed for a few compounds; however, to a large degree they were compensated for by the internal standards used. Deuterium\u2010labelled and <jats:sup>13<\/jats:sup>C\u2010labelled internal standards were used for 8 and 11 of the compounds, respectively. In a comparison between Intercept and Quantisal OF kits, better recoveries and fewer matrix effects were observed for some compounds using Quantisal. The method is sensitive and robust for its purposes and has been used successfully since February 2015 for analysis of Intercept OF samples from 2600 cases in a 12\u2010month period. 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