title: Chiral purity assay for Flindokalner using tandem mass spectrometry: method development, validation, and benchmarking.
abstract: The present work demonstrates the application and validation of a mass spectrometry method for quantitative chiral purity determination. The particular compound analyzed is Flindokalner, a Bristol-Myers Squibb drug candidate for post-stroke neuroprotection. Chiral quantification of Flindokalner was achieved using tandem mass spectrometry (MS/MS) and the kinetic method, a gas phase method used for thermochemical and chiral determinations. The MS/MS method was validated and benchmarked against two separate chromatographic techniques, chiral high performance liquid chromatography with ultra-violet detection (LC/UV) and achiral high performance liquid chromatography with circular dichroism detection (LC/CD). The chiral purity determination of Flindokalner using MS/MS proved to be rapid (3 min run time for each sample) and to have accuracy and precision comparable to the chiral LC/UV and achiral LC/CD methods. This method represents an alternative to commonly used chromatographic techniques as a means of chiral purity determination and is particularly useful in rapid screening experiments.
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN 47907, United States.
authors.forename: Brandy L
authors.initials: BL
authors.lastname: Young
authors.forename: R G
authors.initials: RG
authors.lastname: Cooks
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Madden
authors.forename: Michael
authors.initials: M
authors.lastname: Bair
authors.forename: Jingpin
authors.initials: J
authors.lastname: Jia
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Aubry
authors.forename: Scott A
authors.initials: SA
authors.lastname: Miller
mesh_terms: D019985:Benchmarking; D002853:Chromatography, Liquid; D007700:Kinetics; D015394:Molecular Structure; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification*; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations