Rapid Quantification of Low-Level Crystalline Impurities in Dalmelitinib Mesylate Using NIR Spectroscopy and Chemometric Modeling

Accurate measurement and control of impurities are critical for ensuring the quality and therapeutic performance of solid-state pharmaceutical formulations. This study introduces a rapid, minimal sample preparation analytical approach for quantifying low-level dalmelitinib impurities in dalmelitinib mesylate, employing near-infrared (NIR) spectroscopy combined with partial least squares regression (PLSR). To mimic actual manufacturing conditions, a mixture system was designed comprising dalmelitinib mesylate, dalmelitinib impurity, and formulation excipients. Various spectral preprocessing strategies were systematically evaluated, including Savitzky–Golay first derivative (SG1st), Savitzky–Golay second derivative (SG2nd), multiplicative scatter correction (MSC), standard normal variate (SNV), wavelet denoising, wavelet compression, and their combinations. The optimal model was obtained using SG1st combined with wavelet denoising. The resulting PLSR model (7 latent variables) showed good predictive performance, with an R2 of 0.99569 and an RMSECV of 0.00315. The limit of detection (LOD) and limit of quantification (LOQ) were 0.234% and 0.708%, respectively, demonstrating applicability for monitoring low-level impurities in pharmaceutical formulations. Method validation demonstrated satisfactory precision (RSD < 3%), accuracy (100.77–102.01%), and stability over 24 h (RSD ≤ 4.75%). Compared with conventional solid-state analytical techniques, the proposed NIR–PLSR framework enables rapid, non-destructive analysis with minimal sample preparation. The combination of derivative preprocessing and wavelet denoising improved extraction of impurity-related spectral information in complex pharmaceutical systems, highlighting the potential of this approach for process analytical technology (PAT) and pharmaceutical quality monitoring.