Multi-attribute characterization of pharmaceutical materials by HPLC coupled with charged aerosol detection.

((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol (2S-FHPM) is a common building block in drug molecules, yet its small size and lack of chromophore pose a significant analytical challenge. To address this, we have developed a high performance liquid chromatography-charged aerosol detector (HPLCCAD) method for simultaneous determination of 2S-FHPM assay, chiral and achiral impurities, and counter ion content with a run time of 26 min. The method demonstrated excellent specificity, sensitivity (0.1 %), linearity (R2 > 0.99), and precision (relative standard deviation of retention time and peak area both under 2 %). Furthermore, the accuracy of the method was confirmed by orthogonal techniques of quantitative nuclear magnetic resonance (qNMR) for assay, high performance liquid chromatography-ultraviolet detection (HPLC-UV) with derivatization for chiral impurity, and ion chromatography (IC) for counter ion content. This is the first reported comprehensive characterization of 2S-FHPM using a single, non-derivatizing HPLC method, making it highly suitable for efficient characterization and quality control of 2S-FHPM in the fast-paced drug development phase.