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- Title
Rapid identification of miglitol and its isomers by electrospray ionization tandem mass spectrometry.
- Authors
Yin, Qiuhong; Wang, Lin; Sun, Cuirong
- Abstract
Rationale 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. Methods 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. Results 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-C7H8O]−), m/ z 196 ([M-C7H8O-H2O]−), m/ z 151 ([M-C8H13NO3]−), and m/ z 133 ([M-C8H15NO4]−). The abundances of these fragments are different which are related to the stereostructure of miglitol and its isomers. Conclusions 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.
- Subjects
ELECTROSPRAY ionization mass spectrometry; IMINOSUGARS; TYPE 2 diabetes treatment; ION traps; BORONIC esters
- Publication
Rapid Communications in Mass Spectrometry: RCM, 2016, Vol 30, p155
- ISSN
0951-4198
- Publication type
Article
- DOI
10.1002/rcm.7618