title: Placing supercritical fluid chromatography one step ahead of reversed-phase high performance liquid chromatography in the achiral purification arena: a hydrophilic interaction chromatography cross-linked diol chemistry as a new generic stationary phase.
abstract: A major driving force hindering the application of supercritical fluid chromatography (SFC) to achiral medium-throughput (MT) and/or high-throughput (HT) purification in the pharmaceutical industry is the absence of a widely applicable column for the analysis and purification of structurally diverse research compounds. As a result, method development is more time-consuming compared to reversed-phase high-performance liquid chromatography (RP-HPLC) where 2 stationary phases, each one used at a different pH, can successfully resolve the majority of mixtures, and SFC is considered a step behind this traditional tool. In early 2010, our group identified a hydrophilic interaction chromatography (HILIC) cross-linked diol chemistry as the most generic column tested so far for achiral SFC application. Analytical and semi-preparative pilot studies using internal research mixtures exceeded our best expectations and allowed for the reduction of our initial 5 column screen on diol, 2-ethyl pyridine, benzenesulfonamide, diethylaminopropyl and dinitrophenyl to a one column (HILIC cross-linked diol) or two column (HILIC cross-linked diol and 2-ethyl pyridine) screen for MT and HT purification. This very high-efficiency and cost-effective approach was immediately implemented as our routine process. Since then, scope, generality and robustness have been validated: 85-90% of samples received in our labs can be purified by SFC, 98% of them using the new 1-2 column simplified screening strategy and in a single pass. In addition, the compound of interest (COI) is isolated at greater than 95% purity and with 85-90% recovery. The success of the new approach has enabled the group to shift from RP-HPLC/MS to SFC/MS as the primary technique for purification within the achiral area.
authors.affiliation: Centro de Investigación Lilly, Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain. de_la_puente_maria_luz@lilly.com
authors.forename: M L
authors.initials: ML
authors.lastname: de la Puente
authors.forename: P López
authors.initials: PL
authors.lastname: Soto-Yarritu
authors.forename: C
authors.initials: C
authors.lastname: Anta
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D025924:Chromatography, Supercritical Fluid / Q000295:instrumentation* / Q000379:methods*; D055808:Drug Discovery; D057927:Hydrophobic and Hydrophilic Interactions; D009930:Organic Chemicals / Q000737:chemistry / Q000302:isolation & purification; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000302:isolation & purification; D015203:Reproducibility of Results
chemical_list: D000438:Alcohols; D009930:Organic Chemicals; D004364:Pharmaceutical Preparations