Rapid Quality Screening of Intra-lot Variability of Acetazolamide Using Near-Infrared Spectrometry.

Acetazolamide for Injection, USP is a sterile, preservative-free carbonic anhydrase inhibitor primarily indicated for the treatment of acute mountain sickness, fluid volume overload associated with heart failure, and elevated intraocular pressure in glaucoma. This research utilized Fourier transform near-infrared spectrometry (FT-NIR) to evaluate the intra-lot variability of 12 vials of Mylan Institutional Acetazolamide 500 mg. While all sampled vials appeared visually identical as white to yellowish-white powders, FT-NIR analysis identified significant spectral heterogeneity, particularly in the range of 4200 to 5200 cm-1. Statistical analysis using the Bootstrap Error-Adjusted Single-sample Technique (BEST) and Principal Component Analysis (PCA) identified vial 6 as a prominent statistical outlier. This vial exhibited a distinct absorbance peak at 4851 cm-1, which was suggested to be a shift from a peak at 5173 cm-1 and was positioned 4.03 standard deviations from the center of the lot cluster in multidimensional spectral hyperspace. These results suggest that the manufacturing process may have been operating outside of a state of process control. Given the ongoing national shortages of acetazolamide as of January 2026, such quality assurance screenings are critical for maintaining supply chain transparency and ensuring the reliability of medication used in evolving clinical protocols.