Chiral probe for mass spectrometric identification and quantitation of levodropropizine and its enantiomer, dextrodropropizine

Acyl chlorides react rapidly with hydroxyl and amino groups in the absence of catalysts and therefore hold great promise for chiral mass spectrometry. Herein, a tandem mass spectrometry method based on derivatization with (-)-camphanic acid chloride as a simple chiral probe was developed for the highly sensitive detection and quantitation of levodropropizine and its enantiomer, namely, dextrodropropizine. The diastereomeric derivatization products were quantified based on the relative abundances of their fragment ions produced upon collision-induced dissociation in positive-ion mode. The reactive site was elucidated using nuclear magnetic resonance spectroscopy and two-dimensional total correlation spectroscopy, and the reaction mechanism was proved by stoichiometry studies. The degree of isomer recognition was investigated at different collision energies and determined as R-chiral approximate to 1.5. Thus, this study gives the way to the mass spectrometric identification and quantitation of levodropropizine and its enantiomer, and the developed method represents a new and practical technique for rapid and sensitive determination and quality control of enantiomers of chiral drugs.

Automated summary

A tandem mass spectrometry method based on acyl chlorides was developed for the detection and quantitation of levodropropizine and its enantiomer. The method utilizes the relative abundances of diastereomeric derivatization products produced upon collision-induced dissociation. The reactive site and mechanism were elucidated using nuclear magnetic resonance spectroscopy and stoichiometry studies. The method showed good isomer recognition.