LP Columns: More Than Just Tolerating Strong Acids

The Ultisil family, being Welch Materials' flagship series, has earned broad acceptance across customers worldwide. Within that family, the LP (Low pH) subseries commonly evokes a single, immediate association: resistance to strong acids.

While this association is correct, it only scratches the surface. The LP series’ performance arises from an integrated set of design choices that deliver acid stability while also providing distinctive and useful chromatographic selectivity, and is rooted in three fundamental design elements:

• the introduction of large functional groups on the alkyl side chains;
• a re-hydroxylated silica surface; and
• a deliberate lack of endcapping.

The following discussion examines these elements and explains how they translate into practical advantages for method development.

The degradation of traditional silica-based columns in acidic environments is primarily caused by the hydrolysis of the bonded phase. While the silica matrix itself is acid-resistant, the functional groups—both the primary stationary phase and the endcapping—are susceptible to cleavage.

The LP series addresses this vulnerability by introducing comparatively large functional groups into the alkyl side chains of the bonded phase. These bulkier substituents create steric hindrance that protects the bonded phase from hydrolytic attack under high-temperature, strongly acidic conditions, improving stability in precisely those environments that commonly accelerate degradation.

Beyond protection, these bulky groups provide additional chromatographic benefits through their stronger hydrophobicity and unique spatial structure. As a result, interactions with weakly polar regions of analyte molecules are often significantly stronger than with conventional bonded phases, and special selectivity toward certain structural motifs can be exhibited. Consequently, even though LP phases generally have lower bonding density, their retention of weakly polar compounds is not compromised.

The final, and perhaps most critical, design element is the re-hydroxylated silica surface. While it looked indirect at first glance, it is the most essential process of the LP series, because non-endcapped columns are inherently more sensitive to variations in the underlying silica batches.

The re-hydroxylation process, introduced during column production, treats the silica substrate to eliminate micropores that contribute to reduced column efficiency, and create a smooth surface with a reduced density and uniform distribution of highly acidic silanol sites. As a result, the complex set of interaction mechanisms intrinsic to LP phases is stabilized and batch variability is minimized.

By controlling the silica surface in this way, Welch Materials increases the reproducibility and predictability of LP column behavior, creating a firmer foundation for reproducible method development that leverages the LP series’ distinctive selectivity.

From the design choices described above emerges a consistent philosophy: recognize the intrinsic complexity of the LP stationary phase and make deliberate engineering choices to stabilize and harness that complexity. The LP series is not merely a “strong-acid-tolerant” column family; it is a deliberately crafted stationary phase that combines sterically protected bonded groups, non-endcapped surface functionality, and a re-hydroxylated substrate to deliver acid stability, unique retention behavior for weakly polar analytes, and reduced batch variability.

For method developers, that means treating LP columns as tools with additional interaction modes to exploit—not as aberrant or defective phases to be avoided. When these modes are understood and applied, they broaden the options available during method development and can convert potential disadvantages into reliable, reproducible advantages.

Note: One amino acid in the sequence of this drug intermediate is Asp, and the impurity is β-Asp. No tendency of separation was observed with XS-C18, XB-C18, and C30; only LP-C18 was able to separate them.