Aim: Multiplexed, high-throughput analysis facilitates therapeutic drug monitoring. 14 drugs with various physico-chemical properties were quantitated in dried blood microsamples. Methods: Analytes were extracted employing eight solvent compositions and seven extraction methods. The applicability of liquid serum, dried serum and dried whole blood calibrators was investigated. Results: High recoveries were attained. Calibration using dried serum yielded lowest total error. Reducing sample hematocrit caused outstanding elevations in recovery of analytes with high polarity or affinity to erythrocytes. 9-day analyte stability was demonstrated. Conclusion: Based on the analysis of spiked samples, multiplexed testing of drugs in dried blood microsamples seems feasible, but with analyte-dependent method performance. Dried serum calibration allows the adaptation of serum-based workflows. Further evaluation using real-life specimens is needed.
Keywords: LC–MS/MS; clinical toxicology; dried blood spot; patient compliance; therapeutic drug monitoring; volumetric absorptive microsampling.