Methods and systems for separating, detecting, and/or quantifying sample enantiomers using differential mobility spectrometry (DMS) are provided herein. In accordance with various aspects of the applicant's teachings, the methods and systems can provide for the separation of racemic or non-racemic mixtures of sample enantiomers that may be difficult to separate with conventional techniques, such as mass spectrometry (MS), by reacting the sample enantiomers with an enantiomerically-pure compound to form diastereomers separable by DMS.