Short CommunicationDetermination of Endogenous Concentrations of Uracil and Dihydrouracil in Dried Saliva Spots by LC-MS/MS: Method Development, Validation, and Clinical ApplicationAntunes, Marina Venzon PhD*; Raymundo, Suziane MSc*; Cezimbra da Silva, Anne Caroline BSc*; Muller, Victoria Vendramini BSc*; Vicente Neto, Olavo José MSc*; Schwartsmann, Gilberto PhD†; Linden, Rafael PhD*Author Information *Graduate Program on Toxicology and Analytical Toxicology, Universidade Feevale, Novo Hamburgo; and †Oncology Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil. Correspondence: Marina Venzon Antunes, PhD, Universidade Feevale, ERS 239, no 2755, 93525-075 Novo Hamburgo, Rio Grande do Sul, Brazil (e-mail: [email protected]). Supported by Universidade Feevale and Fundo de Incentivo à Pesquisa e Eventos do Hospital de Clínicas de Porto Alegre (FIPE-HCPA). The authors declare no conflict of interest. Therapeutic Drug Monitoring: June 2019 - Volume 41 - Issue 3 - p 383-390 doi: 10.1097/FTD.0000000000000615 Buy Metrics Abstract Background: The aim of this study was to develop and validate a liquid chromatography–tandem mass spectrometry (LC-MS/MS) assay for the measurement of uracil (U) and dihydrouracil (UH2) concentrations in dried saliva spots (DSSs), for the evaluation of dihydropyrimidine dehydrogenase (DPD) enzyme activity. Results: Nine 18-mm diameter DSS discs were extracted with acetate:isopropyl alcohol (85:15, vol/vol) and analyzed by LC-MS/MS. The assay was linear in the range of 10–1000 ng·mL−1, with accuracy between 89% and 112% and precision between 5.7% and 13%. The metabolic ratio [UH2]/[U] was stable in DSS for up to 9 days at 45°C. Concentrations of U and UH2, as well as the metabolic ratio, were highly concordant between matrices. Using a metabolic ratio classification cutoff of 1.16 for the identification of slow DPD metabolizers, 98.7% concordance was achieved between SS and saliva. Conclusions: DSS samples could be a useful alternative for DPD activity screening, particularly in locations with limited access to highly equipped laboratories. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.