Hermes Licea Pere
GlaxoSmithKline, USA
Title: Applications of supercritical fluid chromatography for chiral metabolite separations in drug metabolism and pharmacokinetics environment
Biography
Biography: Hermes Licea Pere
Abstract
In recent years, interest has expanded to perform chiral separations by supercritical fl uid chromatography (SFC) which
is proven to be superior to conventional liquid chromatography in separating structurally related compounds, such as
diastereoisomers and enantiomers. Several examples will be described for separation of multiple stereoisomers in biological
samples, confi rming SFC to be a powerful tool for stereoisomeric resolution for drug metabolism and pharmacokinetics
(DMPK) applications. Two of these examples are summarized below: Gradient UPLC methodologies have previously been
applied to separate a drug development compound and its six polyoxygenated metabolites (M2-M6 and M13), supporting
numerous non-clinical and clinical PK studies. However, each of these metabolites exists in diff erent stereoisomeric forms,
resulting in 14 separate species. Initial attempts at developing UPLC methodologies were not capable of adequately separating
these complex species; separation was unsuccessful using chemical derivatization, chiral and conventional reversed-phase
liquid chromatography. Th e application of SFC is described herein to separate this complex mixture of 14 stereoisomeric
metabolites; these data provided important data on which species circulate in human. SFC in combination with chemical
derivatization was proven superior for separation of four diastereomeric species of another drug development compound.
Th is method was fully validated and applied to evaluate potential in vivo chiral conversion in pooled clinical and preclinical
samples.