Extended Dynamic Range ELSD For Purification and Impurity Profiling in Pharmaceutical Industry

Rodolphe Pennanec, Ph.D.
CEO
SEDERE

When running impurity profile analysis, dynamic range of the detector is one of the most important parameters. Current norms in pharmaceutical industry require at least 3 orders of magnitude in order being able to quantify 0.1% impurities.

Running low dynamic range detector analysis often requires a multi-injection sequence with external calibration, since it is impossible to get simultaneously a single injection chromatogram with a non-saturated major peak along with minor peaks.

Evaporative Light-Scattering Detection (ELSD) is a nearly universal technique that should be considered as an advantageous alternative to UV detection in impurity profiling, since response factor is generally tighter than with UV detectors, providing a more accurate picture of impurity profile. ELSDs provide a Universal detection mode for most of analysis technologies (Standard HPLC, U-HPLC, GPC, SFC…) and also for purification (CPC, CCC, Flash and Semi-Preparative Chromatography). Low temperature evaporation of the mobile phase (LT-ELSD^TM technology) is mandatory to preserve all solutes from thermal degradation or evaporation/sublimation. The lowest is the evaporation temperature the more universal is the detector (i.e. the ability of the detector to detect thermo-sensitive solutes).

ELSD doesn’t rely on the optical properties of the analyte, making this detection mode ideal for all compounds less volatile than the mobile phase, including those with no chromophore or widely differing extinction coefficients. This detection mode is able to accurately measure a wide range of analytes with consistent responses and is therefore an extremely useful technique to get the complete picture of complex samples. However, in some cases, ELSD does not provide enough dynamic range to assess impurity profile within one chromatogram.

A new generation LT-ELSD^TM equipped with a patented feature is shown to offer an efficient way to override this limitation, providing more than 4 orders of magnitude of dynamic range within a single setting, thus allowing the impurity profiling in one injection. This process is called SAGA^TM (SEDEX Automated Gain Adjustment): Thanks to an innovative design, this new LT-ELS detector is able to adapt in real time the gain setting to avoid any signal saturation and, in the meantime, to provide a quantitative view of the chromatogram with just a single setting. By using this feature, the scale of the chromatogram can freely overshoot up to several volts the standard limits of other ELS detectors, thus drastically enhancing the dynamic range of the detector.

This new feature allows the LT-ELSD^TM to acquire data without limitation in the higher signal range, so that sensitivity is always at the highest setting (no more need for attenuation or gain parameters). This feature also brings a relevant solution:

• In Purification, where the concentration of the sample is generally unknown and for which a signal saturation risk exists and may result in a sample loss.
• In Pharmaceutical analysis, where quality assessment of the products requires an important dynamic range.