Chiral Discrimination of DL-Amino Acids by Trapped Ion Mobility Spectrometry after Derivatization with (+)-1-(9-Fluorenyl)ethyl Chloroformate

Raquel Pérez-Míguez, Ben Bruyneel, María Castro-Puyana, María Luisa Marina, Govert W. Somsen*, Elena Domínguez-Vega

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

A novel analytical method based on hybrid trapped ion mobility spectrometry-time-of-flight mass spectrometry (TIMS-TOFMS) has been developed to achieve fast enantiomeric separation of amino acids (AAs). Resolution of chiral AAs was achieved by forming diastereomers through derivatization with the chiral agent (+)-1-(9-fluorenyl)ethyl chloroformate (FLEC), avoiding the use of reference compounds. Electrospray ionization (ESI) in positive mode yielded sodiated FLEC-AAs ions of which the diastereomers could be separated by TIMS. The effect of other alkali metal ions (such as Li and K) on the enantioselectivity was studied, but chiral discrimination was only observed for Na. TIMS conditions, including voltage ramp, ramp time, and accumulation time were optimized for each AA, and collision cross sections (CCSs) were determined for all diastereomers. The migration order of the DL enantiomers was found to be dependent on the structure of the AA. The resulting TIMS resolution (K0/ΔK0) for the FLEC-AA diastereomers on average was 115, requiring a mobility (K0) difference of about 0.009 cm 2 /(V s) to achieve 50%-valley separation. From the 21 AAs studied, enantiomer separation was achieved for 17 AAs with mobility differences ranging from 0.009 for lysine up to 0.061 cm 2 /(V s) for asparagine. Moreover, the presented methodology provided mutual separation of various AAs, allowing chiral analysis of multiple AAs simultaneously which may be challenging with previous enantioselective IMS approaches. It appeared possible to fully resolve all studied DL-AAs using three distinct TIMS methods, resulting in a total MS run time of about 3 min (1 min per method) and a total analysis time (including derivatization) of less than 15 min. The method demonstrated capable to determine enantiomeric ratios down to 2.5% with detection limits for the D enantiomers in the nanomolar range. This new TIMS-based methodology opens up possibilities for easy and fast analysis of AA enantiomers.

Original languageEnglish
Pages (from-to)3277-3285
Number of pages9
JournalAnalytical Chemistry
Volume91
Issue number5
DOIs
Publication statusPublished - 5 Mar 2019

Funding

R.P.-M., M.C.-P., and M.L.M thank the Spanish Ministry of Economy and Competitiveness (Grant CTQ2016-76368-P) and the Comunidad of Madrid (Spain) and European Funding from the FEDER Program (Grants S2013/ABI-3028, AVANSECAL-CM) for financial support. R.P.-M. thanks the University of Alcalá for her predoctoral contract and the mobility grant to stay at Vrije Universiteit. M.C.-P. thanks the Spanish Ministry of Economy and Competitiveness for their “Ramoń y Cajal” Contract (Grant RYC-2013-12688).

FundersFunder number
Ramoń y CajalRYC-2013-12688
Spanish Ministry of Economy and CompetitivenessCTQ2016-76368-P
Comunidad de Madrid
European Regional Development FundS2013/ABI-3028

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