Development of acid stable, hyper-crosslinked, silica-based reversed-phase liquid chromatography supports for the separation of organic bases

Lianjia Ma, Hao Luo, Jun Dai, Peter W. Carr

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


A new generation of extremely acid stable "hyper-crosslinked" (HC) phases have been developed with good plate counts for basic drug separations. In our previous work, we successfully developed an approach for synthesizing HC stationary phases on silica substrates using aluminum trichloride catalyzed Friedel-Crafts (F-C) chemistry to improve the stability of silica-based RPLC stationary phases at low pH. However, the performance of basic analytes on these HC phases under acidic conditions was unusually poor compared to that of conventional silica-based C18 phases. The effects of the specific F-C catalysts used and the specific silica substrate on the chromatographic properties of HC phases have been studied. Modified synthetic strategies that give both good observed plate counts for basic analytes under acidic conditions and very good low pH stability without compromising other chromatographic properties of the hyper-crosslinked phases have been developed. Replacement of aluminum trichloride with tin tetrachloride as the catalyst for the F-C chemistry and use of a very high purity silica result in significantly improved plate counts for basic analytes. In formic acid buffered mobile phases, which are highly compatible with electrospray ionization LC-MS, basic analytes showed much better performance on the tin tetrachloride catalyzed HC phases than on any conventional commercial phase tested. The tin tetrachloride catalyzed HC phase is as stable as the original aluminum trichloride catalyzed HC phases, and much more stable than the bench mark acid stable commercial phase.

Original languageEnglish (US)
Pages (from-to)21-28
Number of pages8
JournalJournal of Chromatography A
Issue number1
StatePublished - May 5 2006

Bibliographical note

Funding Information:
We thank the National Institutes of Health for the financial support. We thank Mac-Mod Analytical (Chadds Ford, PA, USA) for the donation of the HiChrom silica and ACE C 18 stationary phases, Agilent Technologies Inc. (Wilmington, DE, USA) for the donation of Zorbax silica and SB C 18 phases, and Varian Inc. (Palo Alto, CA, USA) for the donation of an Inertsil ODS 3 column.


  • Acid stability
  • Basic analytes
  • Efficiency
  • HPLC
  • High temperature
  • Pharmaceuticals
  • Proteins and peptides
  • Proteomics
  • Stationary phase


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