Why HPLC-CAD is ideal for quality assurance of APIs and excipients

The gold standard of quality assessment of drugs is nowadays an HPLC using a reversed-phase (RP) column chromatography and aqueous buffers, acetonitrile, and/or methanol as mobile phase, combined with a UV detector.

As many excipients and active pharmaceutical ingredients (APIs) do not have a chromophore, these compounds are not suitable for identification and quantification by UV detection. In this situation, the near-universal Charged Aerosol Detector (CAD) is an excellent alternative capable of detecting almost all non-volatile compounds.

One critical thing to know is that the mobile phase composition—often dictated by solid phase chemistry—can influence the CAD response. In addition to RP techniques, chromatographers often apply ion pair chromatography (IPC), mixed mode (MMC), and hydrophilic interaction (HILIC) methods. We will discuss how these solid phases influence selectivity and sensitivity of the CAD when analyzing the purity of APIs such as amino acids, vigabatrin, ibandronate, atropine, and gabapentin, as well as excipients, e.g., fatty acids, PEGs, and polysorbates.

These examples will demonstrate the versatility of HPLC-CAD for quantifying low concentrations of impurities in APIs and excipients. Sensitivity is of great importance in the quality control of drugs.

Key Learning Objectives:

• Quality assurance by HPLC-CAD, enhancement of sensitivity, impurity profiling of APIs and excipients.

Key learning and takeaways include:

• Explore on the critical yet increasingly complex challenge of impurity profiling of APIs and excipients in pharmaceutical analysis
• Review on enhancement of sensitivity in detection to uncover low-level impurities
• Discover examples for quality assurance by HPLC-CAD analysis

Presenter: Ulrike Holzgrabe (Senior-Professor Pharmaceutical and Medicinal Chemistry, University of Würzburg)

Ulrike Holzgrabe holds a diploma in Chemistry and an approbation in Pharmacy. After habilitation in Kiel she became a professor of Pharmaceutical Chemistry at the University of Bonn and from 1999 till 2022 she holds a chair of Pharmaceutical and Medicinal Chemistry in Würzburg. She served for some 25 years as an expert of the German pharmacopoeia commission (at BfArM) and for 18 years as an expert and president of two expert groups at the European Directorate of the Quality of Medicines and HealthCare (EDQM). She has published 500+ papers in the field of quality assurance of drugs and medicinal chemistry.

Presenter: Frank Steiner (Senior Manager of Product Applications, Thermo Fisher Scientific)

Frank Steiner is the Senior Manager of Product Applications and helps coordinate scientific collaborations at Thermo Fisher Scientific. He received his Ph.D. in Analytical Chemistry from Saarland University in Saarbrücken, Germany, and has published 30+ publications in refereed journals and 10+ textbook chapters on HPLC topics.