Separation and identification of a complex flurbiprofen-polyethylene glycol mono- and diester mixture via a hyphenated HPLC-DAD-HRMS/SPE NMR system.

We report the use of a hyphenated HPLC-DAD(diode array detector)-HRMS/SPE NMR system for the separation and isolation of a complex mixture of esters, containing substances with very similar LC retention times. The literature known mono- and diesters of the drug Flurbiprofen and polyethylene glycol, which form a large number of substances with varying chain lengths, were chosen for this study. We demonstrate the use of this hyphenated system to quickly and effectively isolate sixteen of these highly similar individual esters in an automated fashion, demonstrating its applicability in standard pharmaceutical analysis and quality control of drugs. Both, synthetic solutions of these esters and extracts from Flurbiprofen lozenges were used for this purpose. By the sole use of this system, the individual compounds were isolated and UV, HRMS and 1D and 2D NMR data could be collected, enabling the identification and differentiation of the individual esters.

Isolation, Identification and Structural Verification of a Methylene-Bridged Naloxone "Dimer" Formed by Formaldehyde.

We report the isolation and characterization of a methylene bridged "dimer" of the opioid antagonist Naloxone, previously detected in experimental Buprenorphine-Naloxone oral films. This compound was found to form via an aldol addition followed by a condensation reaction under acidic conditions between two units of Naloxone and one unit of formaldehyde. HPLC-UV-HRMS analysis revealed the formation of three individual stereoisomers during this reaction, which were separately isolated using solid-phase extraction. These isomers were shown to freely react into one another in solvent, forming an equilibrium. The structure of the unknown compound was determined via HRMS spectrometry and 1D and 2D NMR spectroscopy.

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

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.