The foremost objective of the present study was to develop and validate a new LC-QTOF-MS/MS method for the identification and quantitative determination of 4,6-dichloro-5-nitro-2-(propylthio)pyrimidine (DPP) genotoxic impurity through the derivatization process in ticagrelor active pharmaceutical ingredient (API). Owing to the low response of DPP at the specification level, DPP was converted to 4,6-dibenzylamino-5-nitro-2-(propylthio)pyrimidine (DPP derivative) by addition of benzyl amine, then analyzed using mass spectrometry with a time-of-flight analyzer, and good separation was accomplished under the experimental conditions described.The effective separation of DPP derivative was achieved using an Acquity UPLC BEH C 18 reverse-phase column (100  4.6 mm  1.7 μm) with an isocratic program with mobile phase A as 0.1% formic acid in milli Q water and mobile phase B as acetonitrile in the ratio of 20:80 v/v. The flow rate was maintained as 0.4 ml/min, the injection volume was 2 μl, the autosampler temperature was 5 C, the column oven temperature was ambient and the run time was 6.0 min. The diluent used was 0.2% benzyl amine in water and acetonitrile in the ratio of 30:70 v/v. The retention time of the DPP derivative was 2.87 min. The limit of detection and limit of quantification were 0.03 and 0.08 ppm, respectively. The DPP derivative was linear from 1.68 to 12.78 ppm with R 2 of 0.9958. Thus, the developed method is valid for the identification and quantitative determination of DPP derivative in ticagrelor API. K E Y W O R D S 4,6-dibenzylamino-5-nitro-2-(propylthio)pyrimidine (DPP derivative), genotoxic impurity, LC-ESI-QTOF-MS/MS, ticagrelor, time-of-flight analyzer 1 | INTRODUCTION Ticagrelor is an antiplatelet agent used to thin the blood in patients with acute coronary syndromes (Danielak et al., 2018). It inhibits platelet aggregation in coronary blood vessels and reduces cardiovascular death and heart attack by preventing the formation of new blood clots (

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A new reverse phase and short run time (3.0 min) liquid chromatography–quadrupole time of flight‐tandem mass spectrometry method was developed and validated for identification and ultra‐trace level quantification (0.83 ppm) of genotoxic impurity 1,3‐diacetoxy‐2‐(acetoxymethoxy) propane in valganciclovir hydrochloride active pharmaceutical ingredient. The method is cost effective, time saving and proficient to confirm the parent and fragment ion masses through mass spectrometry and tandem mass spectrometry further fragmentation. An isocratic program and acquity bridged ethylene hybrid C18 reverse phase column (100 mm × 4.6 mm × 1.7 μm) was used to accomplish optimum separation between valganciclovir and 1,3‐diacetoxy‐2‐(acetoxymethoxy) propane impurity. Mobile phase‐A used was 0.1% formic acid in milli Q water and mobile phase‐B used was acetonitrile in the ration of 50:50 v/v. Diluent used was water and methanol in the ratio of 30:70 v/v. Chromatographic conditions are selected as injection volume: 3 μL, flow rate: 0.2 mL/min, oven temperature: ambient, auto sampler: 5°C and run time: 3.0 min. The retention time of 1,3‐diacetoxy‐2‐(acetoxymethoxy) propane impurity was found at 1.830 min. The detection and quantification levels found at 0.027 and 0.083 ppm. The 1,3‐diacetoxy‐2‐(acetoxymethoxy) propane impurity is linear from 0.082 to 1.236 ppm levels with regression coefficient 0.9972. The recoveries were from 93.3 to 110.0%.