The detection of related substances in both active pharmaceutical ingredients (APIs) and dosage forms, especially via process analytical technology (PAT), is of crucial importance for the assurance of pharmaceutical quality and clinical safety. However, this process remains a formidable challenge because related substances are structurally similar to APIs, resulting in severe spectral overlap. Herein, we present a host-guest doping room-temperature phosphorescence (RTP) sensing strategy that facilitates rapid detection of impurities in naproxen APIs and dosage forms. Leveraging the low luminescence efficiency at minimal host content, the platform can sensitively detect trace impurities, 2-acetyl-6-methoxynaphthalene (MANAP), in naproxen APIs, achieving a limit of detection (LOD) of 0.05% (w/w), which satisfies the pharmacopeial threshold of 0.1% (w/w). The method demonstrates statistical equivalency to HPLC, with average recovery rates of 98.03%-103.38%. Furthermore, both spectral analysis and real-time visualization inspection were successfully achieved for the limit test of MANAP in naproxen granules and tablets. This work introduces a novel RTP-based PAT approach for impurity testing in pharmaceutical manufacturing.
Zhu et al. (Mon,) studied this question.