Quantitative analysis of Form II in albendazole formulations using near-infrared spectroscopy and partial least squares analysis

Albendazole (ABZ) exists as two solid-state isomers: the amino form (Form I) and the imino form (Form II). While Form II significantly influences bioavailability, current analytical methods primarily focus on qualitative identification of polymorphs or quantify only Form I in raw materials. To address the lack of quantitative methods for both isomers in formulations, we developed a novel near-infrared (NIR) spectroscopy–based approach. This work established a validated quantitative model. ABZ Form II was prepared and characterized via X–ray diffraction, thermal analysis, and Raman imaging. Commercial albendazole tablets were simulated by spiking Form II into excipients at gradient concentrations (5–95 % w/w). The near-infrared (NIR) spectra were screened with preprocessing methods and wavenumber regions. A Factor was set that included the comprehensive determination coefficient (R²), root mean square error of cross validation (RMSECV), Bias and relative percentage deviation (RPD). Models with a Factor score < 0.5 or recovery rates outside 90–110 % were excluded. The method demonstrated high precision (RSD = 0.07 %), with LOD and LOQ values of 0.7840 ± 0.0028 % w/w and 3.0243 ± 0.0139 % w/w, respectively. In summary, this is the first reported NIR method for simultaneous quantification of ABZ Form I and Form II in tablets, providing a rapid, non–destructive tool for pharmaceutical quality control