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Inflammation is associated with hydroxyl radical damage to DNA as a result of oxidative stress. 8-Hydroxy deoxyguanosine (8-OHdG) is a marker of this process and its levels in saliva could be linked to the severity of periodontal inflammation. The aim of this study was to test the sensitivity of liquid chromatography with tandem mass spectrometry (LC-MS/MS) in comparison to enzyme-linked immune sorbent assay (ELISA) for the detection of 8-OHdG in saliva in patients with chronic periodontitis before and after periodontal treatment.Saliva samples were collected from 23 patients (eight females and 15 males; 46.1 ± 5.1 years of age) with generalized chronic periodontitis and 25 (15 females and 10 males; 44.9 ± 6.8 years of age) periodontally healthy individuals. Patients received initial periodontal treatment consisting of scaling and root planing and were evaluated at baseline and after 6 wk of completion of non-surgical therapy. Salivary 8-OHdG levels were measured using ELISA and LC-MS/MS before and after the treatment. Clinically, plaque index, gingival index, clinical attachment level, bleeding on probing, gingival recession and probing pocket depth were measured at baseline and after 6 wk.Salivary levels of 8-OHdG decreased significantly after the non-surgical periodontal treatment (p < 0.001). Statistically significant positive correlations were observed between plaque index, gingival index, probing pocket depth, clinical attachment level, bleeding on probing values and LC-MS/MS and ELISA levels of 8-OHdG (p < 0.001).LC-MS/MS is a reliable and sensitive method for evaluating salivary 8-OHdG levels to monitor the treatment response of periodontitis.