title: A review of recent advances in mass spectrometric methods for gas-phase chiral analysis of pharmaceutical and biological compounds.
abstract: Chirality has been of great interest in pharmaceutical and biological sciences. The capabilities of mass spectrometry (MS) for rapid analysis of complex mixtures have encouraged its exploration for gas-phase chiral differentiation. Although particular instances of successful discrimination between enantiomers have been reported over the past three decades, a general method of quantitative chiral analysis by MS has only been demonstrated recently. This review describes the current state of the chiral MS methods without chiral chromatographic separation, which fall into five main categories: (1) the kinetic method, (2) host-guest (H-G) diastereomeric adduct formation, (3) ion/molecule (equilibrium) reactions, (4) collision-induced dissociation (CID) of diastereomeric adducts, and (5) the emerging technique for gas-phase separation using ion mobility spectrometry (IMS). It emphasizes tandem mass spectrometry (MS/MS), which provides several unique analytical advantages for quantitative chiral analysis. These include intrinsically high sensitivity, molecular specificity, and tolerance to impurities as well as the simplicity and speed of the mass spectrometric measurements. Practical prospects and current challenges in quantitative chiral MS techniques for QbD (quality-by-design)-based pharmaceutical applications are also discussed.
authors.affiliation: API Chemistry and Analysis, Product Development, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA. lianming.2.wu@gsk.com
authors.forename: Lianming
authors.initials: L
authors.lastname: Wu
authors.forename: Frederick G
authors.initials: FG
authors.lastname: Vogt
mesh_terms: D002623:Chemistry Techniques, Analytical; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D005740:Gases; D006801:Humans; D007477:Ions; D007700:Kinetics; D013058:Mass Spectrometry / Q000379:methods*; D008956:Models, Chemical; D015203:Reproducibility of Results; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013678:Technology, Pharmaceutical / Q000379:methods; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D005740:Gases; D007477:Ions