, ,

By Fabio Garofolo

Fabio Garafolo-finalThe latest generation of high resolution mass spectrometry (HRMS) instruments provides pharmaceutical researchers with a more sensitive, selective, and now also robust and easy-to-use analytical technique. HRMS has been traditionally used in drug discovery, and it quickly evolved as an efficient tool for a simultaneous qualitative and quantitative (Qual/Quan) analysis on a single instrument. More recently, HRMS showed its ability to successfully perform in a purely quantitative field and meet all the bioanalytical requirements. Indeed, several publications described HRMS usage in overcoming severe “Quan/Quan” bioanalytical challenges by establishing itself as a leading technique with performance superior to the LC-MS/MS Triple Quad when dealing with very complex applications.

After drug discovery and bioanalysis, what’s the next task for HRMS?

Triple Quad was introduced by Marcello Marchetti, Ph.D., at the beginning of the 1990s at Angelini Pharma and, under his leadership, it quickly became vital to multiple drug discovery and development activities. Afterward, in parallel with the continuous upgrade of the Triple Quad platform, HRMS was implemented at Angelini and started to be more and more used outside its traditional applications. Indeed, the latest applications of HRMS are in unusual fields for this technique such as in analytical development for the quantification of impurities of active pharmaceutical ingredients (API).

Angelini’s work, presented at this year’s AAPS Annual Meeting and Exposition on Monday, October 26, shows a novel application of HRMS in a regulated environment, where a UPLC-QTOF method was used for the determination of TRC-F and CRC-A and its performance was compared with traditional LC-MS/MS procedure reported in the Trazodone hydrochloride USP monograph. The validation results showed that the UPLC-QTOF method was comparable to the USP LC-MS/MS method for linearity, sensitivity, accuracy, and precision. HRMS increased the selectivity, whereas UPLC reduced run time and mobile phase consumption.

However, we also believe that the use of this state-of-the-art analytical technique should not produce a reduction of sample preparation and chromatography separation which are still fundamental components of a robust and reliable analytical methodology. In fact, a fully optimized sample clean-up and well-developed chromatography have a synergic effect when coupled with a powerful instrument like HRMS and have a major impact on method performance. This statement is demonstrated by the poster presented by Valentina Renzi, Ph.D., on Thursday, October 29. Her presentation is focused on maximizing method performance by optimizing and fine tuning each analytical conditions (extraction + chromatography + mass spectrometry) to analyze multiple molecules with very different physico-chemical properties with the same method.

These novel applications of HRMS demonstrate that this technology is quickly expanding in the pharmaceutical industry from its initial use in drug discovery, to bioanalysis and now also in analytical development for quantification of API in a strict regulated environment with performance comparable to official USP methods.

Join us on Oct. 26 and 29 to discuss the latest application of HRMS in the pharmaceutical industry.

Fabio Garofolo, Ph.D., has been working in the pharmaceutical and analytical fields since 1989. He is the head of research at Angelini Pharma and AAPS LBABFG Steering Committee member and LBA Technologies DG cochair.