{"id":19198,"date":"2025-10-07T08:56:14","date_gmt":"2025-10-07T08:56:14","guid":{"rendered":"https:\/\/www.thermofisher.com\/blog\/analyteguru\/?p=19198"},"modified":"2026-04-27T15:43:06","modified_gmt":"2026-04-27T15:43:06","slug":"how-to-get-more-accurate-hplc-quantitation-of-semi-volatiles","status":"publish","type":"post","link":"https:\/\/www.thermofisher.com\/blog\/analyteguru\/how-to-get-more-accurate-hplc-quantitation-of-semi-volatiles\/","title":{"rendered":"How to Get More Accurate HPLC Quantitation of Semi-Volatiles"},"content":{"rendered":"\n

Struggling to accurately measure semi-volatile analytes? Stricter temperature control with HPLC-CAD analysis just might be the solution you need.<\/h3>\n\n\n\n
\"Temperature<\/figure>\n\n\n\n

The charged aerosol detector (CAD) is cited as one of the most capable near-universal HPLC detectors available because the response is solely based on particle charge and fully independent of chemical structure.<\/p>\n\n\n\n

One caveat to know is your mobile phase components must be less volatile than the analytes in solution for detection by the CAD. And while all non-volatiles give a similar uniform response, the response of semi-volatiles<\/a> depends on volatility and consequently is less predictable.<\/p>\n\n\n\n

So, the question then becomes is there a way to address this performance difference and make semi-volatile detection more predictable? One approach for charged semi-volatile analytes is to add a volatile ion-pairing agent of the opposite charge in the mobile phase to force non-volatile behavior.<\/p>\n\n\n\n

However, this method is analyte specific and may also react with impurities in your mobile phase, leading to higher noise and poorer signal-to-noise (S\/N) ratio.  What\u2019s really needed is a more global approach to improve the accuracy for measuring semi-volatiles.<\/p>\n\n\n\n

This approach is now achievable with Temperature Coupling Mode (TCM) in the Thermo Scientific Vanquish CAD P Series<\/a>.<\/p>\n\n\n\n

Why stricter temperature control matters for measuring semi-volatiles<\/strong><\/h3>\n\n\n\n

Before we get into the specifics, you need to understand why temperature control in the CAD is critical to quantitative accuracy, especially for semi-volatiles (Figure 1<\/strong>).<\/p>\n\n\n\n

\"Illustration<\/figure>\n\n\n\n

Figure 1<\/strong>. Illustration showing how the CAD works.<\/p>\n\n\n\n

The two most important functional components in the CAD that guide sensitivity<\/a> are the evaporation tube temperature (EvapT<\/strong>) and the charging detection module (CDM<\/strong>).<\/p>\n\n\n\n