Rapid identification of miglitol and its isomers by electrospray ionization tandem mass spectrometry

Miglitol (1) derived from 1-deoxynojirimycin is an iminosugar that is useful in the treatment of type 2 diabetes mellitus. Isomers (2, 3, 4) that differ at the C2 and C3 positions of hydroxyl groups from miglitol are impurities resulting from the synthesis of miglitol. The impurity profile of a drug substance is critical to its safety assessment and is important for monitoring the manufacturing process. Therefore, developing a fast and simple method that can rapidly identify the configuration of miglitol and its isomers (2, 3, 4) is necessary.

Miglitol (1) and its isomers 2-4 were derivatized with benzoboroxole (o-hydroxymethyl phenylboronic acid) at room temperature, and the cyclic boronate esters of different configurations were generated. Protonated miglitol and its isomers 2-4, as well as their derivatives, were subjected to collision-induced dissociation (CID) experiments by using electrospray ionization tandem mass spectrometry (ESI-MS/MS). Elemental compositions of all the ions were verified by electrospray ion-trap time-of-flight mass spectrometry.

Fragmentation of the protonated miglitol and its isomers gave the same fragment ions at m/z 190 and m/z 146. Both their fragmentation behavior and abundances were similar. Whereas the CID mass spectra of the precursor ions (m/z 322) of cyclic boronate esters showed four characteristic fragment ions, m/z 214 ([M-C7 H8 O](-) ), m/z 196 ([M-C7 H8 O-H2 O](-) ), m/z 151 ([M-C8 H13 NO3 ](-) ), and m/z 133 ([M-C8 H15 NO4 ](-) ). The abundances of these fragments are different which are related to the stereostructure of miglitol and its isomers.

A facile method was established for the differentiation of the spatial configuration of miglitol and its isomers using the relative abundances of the fragment ions of boronate esters generated from in-situ reaction between analytes and benzoboroxole by ESI-MS/MS. This approach could be used to rapidly identify the stereoisomers and monitor the epimerization of miglitol and its isomers in chemical reactions and manufacturing processes. Copyright © 2016 John Wiley & Sons, Ltd.