Chiral purity assay for Flindokalner using tandem mass spectrometry: method development, validation, and benchmarking.
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.
Young
Brandy L
BL
Department of Chemistry, Purdue University, West Lafayette, IN 47907, United States.
Cooks
R G
RG
Madden
Michelle C
MC
Bair
Michael
M
Jia
Jingpin
J
Aubry
Anne-Françoise
AF
Miller
Scott A
SA
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*
D004364:Pharmaceutical Preparations