Rapid method development for chiral separation in drug discovery using sample pooling and supercritical fluid chromatography–mass spectrometry

Theory and Practice of UHPLC and UHPLC–MS

“…November 2016. Płotka et al, 2014;Zhao et al, 2003). Consequently, several research groups focus on the development of high throughput chiral screening strategies (Nováková and Dousa, 2017;De Klerck et al, 2012a,b;Maftouh et al, 2005;White, 2005).…”

Chiral separations in sub‐ and supercritical fluid chromatography

“…The paper demonstrates that the effect of additives can be opposite, depending on the type of CSP used, so their concentration is preferably optimized during method development. Zhao et al [23] proposed an SFC-MS system for chiral method development. Four polysaccharide-based CSPs were installed in an oven with automatic column switcher, and screened in the sequence Chiralpak AD A Chiralpak AS A Chiralcel OJ A Chiralcel OD using gradient elution with MeOH as organic modifier and 0.2% isopropylamine for basic compounds or 0.1% TFA for other compounds as mobile phase additives.…”

Supercritical fluid chromatography‐mass spectrometry for chemical analysis

“…In the drug discovery environment, there is a need to explore the biological responses of new chemical entities with respect to stereochemistry as part of lead characterization [37]. For the development of new stereoisomeric drugs, the quantitative methods for measuring individual enantiomers in in vivo samples are required to support the pharmacokinetics of a single enantiomer or mixture of enantiomers [37]. For the chromatographic resolution of chiral compounds, SFC was proven to provide at least two times faster separation than normal-phase HPLC [36,37].…”

“…For the development of new stereoisomeric drugs, the quantitative methods for measuring individual enantiomers in in vivo samples are required to support the pharmacokinetics of a single enantiomer or mixture of enantiomers [37]. For the chromatographic resolution of chiral compounds, SFC was proven to provide at least two times faster separation than normal-phase HPLC [36,37]. As an example, a chiral packed-column SFC system linked with APCI-MS was reported for the simultaneous determination of (R,S)-propranolol and (+)-pindolol in metabolic stability samples and mouse blood samples [28,29] (Fig.…”