Cong Bi*, Yueer Shi, Wei Ding, James Chadwick, Yan Zha, Su Pan, Paul Foy, Nicola Hulme and Brent Kleintop,
{"title":"Robust Liquid Chromatography–Mass Spectrometry Determination of Deuterium Isotopologues for Quality Control of Deucravacitinib Using Nominal Mass Instrumentation","authors":"Cong Bi*, Yueer Shi, Wei Ding, James Chadwick, Yan Zha, Su Pan, Paul Foy, Nicola Hulme and Brent Kleintop, ","doi":"10.1021/acs.oprd.4c0036110.1021/acs.oprd.4c00361","DOIUrl":null,"url":null,"abstract":"<p >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 <i>d</i><sub>3</sub>-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.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"28 12","pages":"4380–4391 4380–4391"},"PeriodicalIF":3.1000,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Process Research & Development","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.oprd.4c00361","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
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.
期刊介绍：
The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.
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