title: A new method to identify hydrolytic degradants in drug substances with UPLC-MS using ¹⁸O-labelled water.
abstract: Drug substances are susceptible to many different degradation pathways due to diverse nature of the molecule structures. Hydrolysis is one of the most common reactions seen for drug substances and drug products since water is ubiquitously present either as moisture or included in some formulations such as parenteral products. The hydrolytic degradation of fluticasone propionate, duloxetine and amlodipine was studied in this work using (18)O-labelled water with UPLC-MS. The structural proposals of the degradants are based solely on the molecular mass of the degradants with enhanced certainty by corresponding results from (18)O labeling experiments. The advantage of using (18)O labeling experiments is the extra information from knowing whether a water molecule is incorporated into a degradant or not, therefore enabling either confirmation or rejection of a proposed molecular structure.
authors.affiliation: PharmDev, AstraZeneca R&D, Pepparedsleden 3, 43183 Mölndal, Sweden. Electronic address: Jufang.wu-ludvigsson@astrazeneca.com.
authors.forename: Jufang
authors.initials: J
authors.lastname: wu Ludvigsson
authors.affiliation: PharmDev, AstraZeneca R&D, Pepparedsleden 3, 43183 Mölndal, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Andersson
authors.affiliation: PharmDev, AstraZeneca R&D, Pepparedsleden 3, 43183 Mölndal, Sweden.
authors.forename: Viktor
authors.initials: V
authors.lastname: Kjellberg
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006868:Hydrolysis; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D008970:Molecular Weight; D010103:Oxygen Isotopes / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D010103:Oxygen Isotopes; D014867:Water
keywords: Degradation; Drug substance; H(2)O(18); Hydrolysis; UPLC-MS