Formation of a Thiol–Ene Addition Product of Asthma Medication Montelukast Caused by a Widespread Tin-Based Thermal Stabilizer

Abstract

We report the formation and characterization of two diastereomeric thiol–ene addition products of the asthma medication Montelukast within chewing tablets. Widespread tin-based thermal stabilizers dioctyltin bis­(2-ethylhexyl thioglycolate) and monooctyltin tris­(2-ethylhexyl thioglycolate), used in the manufacturing process of the medication’s forming foil, were identified as the source of the thiol reactant, showing that these stabilizers may play a part in the degradation of Montelukast and APIs with functionalities similar to those of Montelukast, which should be considered during development of medication. The isolation and analysis of these impurities was performed by HPLC and UV–vis spectroscopy. HRMS and NMR data were collected to characterize and determine the structures of these compounds.

Benzyl thioether formation merging copper catalysis

“… 3 As an important structural unit, thioethers widely exist in natural products, 4 drugs 2,5 and organic functional materials. 3 a ,6 For example ( Scheme 1A ), montelukast 7 is a selective leukotriene receptor antagonist approved for oral treatment of asthma and allergic rhinitis. Ufiprazole 8 can be used to treat acid related diseases such as peptic ulcer and gastroesophageal reflux disease.…”