Increasing Your Return on Instrument Investment

By Richard Lake, Pharmaceutical Market Development Manager, Restek

Improving data quality and streamlining operations, while decreasing costs and drug development time, are ongoing goals for pharmaceutical labs. Significant investments have been made in UHPLC platforms and mass spectrometry technology to improve productivity. However, these assets cannot perform optimally if chromatographic separations are not adequate, as is often the case when attempting to separate drug compounds on C18 columns.

Phenyl columns offer some aromatic selectivity, but little hydrophobic retention. Restek's unique Biphenyl phase incorporates a novel end-to-end bonding that is a significant advance in phenyl columns, providing both high hydrophobic retention and aromatic selectivity in a single column. These attributes maximize versatility and can be used to increase utilization and return on investment for UHPLC and LC/MS systems.

Proper column choice

UHPLC in the pharmaceutical laboratory is commonly used to accelerate development of methods, which are then scaled to a conventional HPLC-based platform for routine analysis. This common application of UHPLC makes the need for selective column phases just as great in UHPLC as in HPLC. While UHPLC does produce significant gains in efficiency and speed, the gain is not so extreme that stationary phase is inconsequential; selectivity is still the driving force behind separations, as it affects resolution to the greatest mathematical degree.

Higher quality separations, not just faster separations, are needed by pharmaceutical laboratories. To fully realize the potential of UHPLC, labs need to consider both speed and selectivity. Biphenyl columns offer both C18-like and phenyl-like selectivity (easily controlled with mobile phase choice), and, when used in conjunction with UHPLC, they can provide much faster and more effective resolution for drug substances and impurities.

LC/MS asset

Novel Biphenyl column chemistry also can increase return on investment for mass spectrometers. Here, the benefit is not so much selectivity (the mass spectrometer can provide deconvolution) as it is increased retention. Since Biphenyl columns strongly retain analytes, highly organic mobile phases are used to elute the compounds into the mass spectrometer. This leads to higher sensitivities in electrospray ionization as desolvation of the mobile phase becomes more efficient, ultimately giving better ionization.

Another advantage of using highly retentive stationary phases, like Biphenyl, for mass spectrometry is eliminating unwanted adduct formation or charge competition from matrix interferences that are less retained by the column. Commonly used C18 columns are excellent for retaining hydrophobic solutes, but fail when retaining hydrophilic solutes. In contrast, Biphenyl columns are capable of retaining both hydrophilic and hydrophobic aromatics better than conventional C18 and phenyl phases, resulting in a wider range of applications and better mass spectrometer asset utilization

Alternative and easily controlled selectivities give Biphenyl columns a unique versatility, leading to a higher return on investment and better utilization of instrument resources. Since Biphenyl columns offer both aromatic selectivity and hydrophobic retention, orthoganol separations can be achieved with simple mobile phase changes. This 'tunable' selectivity gives markedly better separations for molecules differing in degree of unsaturation, double bond position, or electron withdrawing groups.

Improved MS sensitivity is also possible, due to the use of more organic mobile phases. Biphenyl columns are available on a variety of silicas, including a fully scalable line accommodating UHPLC-HPLC method transfer. Versatile Biphenyl columns can improve utilization of UHPLC and LC/MS resources and are an ideal tool for method development.

For more information, visit www.restek.com/biphenyl.

Richard Lake is the Pharmaceutical Market Development Manager at Restek Corporation. He is responsible for overseeing the development and application of chromatographic products for the pharmaceutical industry. He has over 13 years' experience, including positions as lead chemist, LC and GC method developer, stability manager and study director for pharmaceutical studies.