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Many forensic laboratories experience backlogs due to increased drug-related cases. Laser diode thermal desorption (LDTD) has demonstrated its applicability in other scientific areas by providing data comparable with instrumentation, such as liquid chromatography-tandem mass spectrometry, in less time. LDTD-MS-MS was used to validate 48 compounds in drug-free human urine and blood for screening or quantitative analysis. Carryover, interference, limit of detection, limit of quantitation, matrix effect, linearity, precision and accuracy and stability were evaluated. Quantitative analysis indicated that LDTD-MS-MS produced precise and accurate results with the average overall within-run precision in urine and blood represented by a %CV <14.0 and <7.0, respectively. The accuracy for all drugs in urine ranged from 88.9 to 104.5% and 91.9 to 107.1% in blood. Overall, LDTD has the potential for use in forensic toxicology but before it can be successfully implemented that there are some challenges that must be addressed. Although the advantages of the LDTD system include minimal maintenance and rapid analysis ( approximately 10 s per sample) which makes it ideal for high-throughput forensic laboratories, a major disadvantage is its inability or difficulty analyzing isomers and isobars due to the lack of chromatography without the use of high-resolution MS; therefore, it would be best implemented as a screening technique