دورية أكاديمية
Two-dimensional reversed phase-normal phase liquid chromatography for simultaneous achiral-chiral analysis to support high-throughput experimentation.
| العنوان: | Two-dimensional reversed phase-normal phase liquid chromatography for simultaneous achiral-chiral analysis to support high-throughput experimentation. |
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| المؤلفون: | Chin S; Department of Small Molecule Analytical Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States. Electronic address: chin.steven@gene.com., Cruz K; Department of Small Molecule Analytical Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States., Goyon A; Department of Small Molecule Analytical Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States., Venkatramani CJ; Department of Small Molecule Analytical Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States., Yehl PM; Department of Small Molecule Analytical Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States., Kurita KL; Department of Small Molecule Analytical Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States. Electronic address: kurita.kenji@gene.com. |
| المصدر: | Journal of chromatography. A [J Chromatogr A] 2023 Mar 15; Vol. 1692, pp. 463820. Date of Electronic Publication: 2023 Feb 03. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 9318488 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3778 (Electronic) Linking ISSN: 00219673 NLM ISO Abbreviation: J Chromatogr A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier, 1993- |
| مواضيع طبية MeSH: | Chromatography, Reverse-Phase*/methods , Research Design*, Solvents/chemistry ; Water ; Stereoisomerism |
| مستخلص: | Typical chromatographic analysis of chiral compounds requires the use of achiral methods to evaluate impurities or related substances along with separate methods to evaluate chiral purity. The use of two-dimensional liquid chromatography (2D-LC) to support simultaneous achiral-chiral analysis has become increasingly advantageous in the field of high-throughput experimentation where low reaction yields or side reactions can lead to challenging direct chiral analysis. Advancements in multi-dimensional chromatography have led to the development of robust 2D-LC instrumentation with reversed phase solvent systems (RPLC-RPLC) enabling this simultaneous analysis, eliminating the need to purify crude reaction mixtures to determine stereoselectivity. However, when chiral RPLC cannot separate a chiral impurity from the desired product, there are few viable commercial options. The coupling of NPLC to RPLC (RPLC-NPLC) continues to remain elusive due to solvent immiscibility between the two solvent systems. This solvent incompatibility leads to lack of retention, band broadening, poor resolution, poor peak shapes, and baseline issues in the second dimension. A study was conducted to understand the effect of various water-containing injections on NPLC and applied to the development of robust RPLC-NPLC methods. Following thoughtful consideration and modifications to the design of a 2D-LC system in regards to mobile phase selection, sample loop sizing, targeted mixing, and solvent compatibility, proof of concept has been demonstrated with the development of reproducible RPLC-NPLC 2D-LC methods to perform simultaneous achiral-chiral analysis. Second dimension NPLC method performance proved comparable to corresponding 1D-NPLC methods with excellent percent difference in enantiomeric excess results ≤ 1.09% and adequate limits of quantitation down to 0.0025 mg/mL for injection volumes of 2 µL, or 5 ng on-column. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023. Published by Elsevier B.V.) |
| المشرفين على المادة: | 0 (Solvents) 059QF0KO0R (Water) |
| تواريخ الأحداث: | Date Created: 20230216 Date Completed: 20230228 Latest Revision: 20230228 |
| رمز التحديث: | 20230228 |
| DOI: | 10.1016/j.chroma.2023.463820 |
| PMID: | 36796276 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-3778 |
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| DOI: | 10.1016/j.chroma.2023.463820 |