Robust Liquid Chromatography–Mass Spectrometry Determination of Deuterium Isotopologues for Quality Control of Deucravacitinib Using Nominal Mass Instrumentation

Deuterated drug molecules are a growing area of interest in the pharmaceutical industry, and controlling isotopologue impurities can be vital due to potential toxicity and efficacy concerns. The limited number of analytical approaches reported for this purpose often relies on high-end instrumentation that is not readily available in quality control (QC) laboratories. We developed and validated a robust liquid chromatography–mass spectrometry (LC–MS) method for the determination of isotopologue impurities in the deuterated drug SOTYKTU (deucravacitinib) using QC-friendly nominal mass LC–MS instruments. The method conditions were systematically evaluated and optimized to ensure key performance attributes, and the method was extended to assess isotopologue impurities in the input material d3-methylamine hydrochloride via an efficient derivatization procedure. The established conditions demonstrated excellent robustness and reproducibility, facilitating successful transfer from development laboratories to commercial QC laboratories. The successful implementation in the release testing of both input reagent and the final drug substance highlights the practical application of nominal mass LC–MS for the determination of the isotopic purity in pharmaceutical development.