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

Area of Science:

• Pharmaceutical Sciences
• Analytical Chemistry
• Spectroscopy

Background:

• Acetazolamide is a vital carbonic anhydrase inhibitor used for acute mountain sickness, heart failure, and glaucoma.
• Ensuring drug quality and consistency is crucial, especially during national shortages.
• Visual inspection alone is insufficient for detecting subtle intra-lot variations.

Purpose of the Study:

• To assess the intra-lot variability of Acetazolamide for Injection, USP using FT-NIR spectrometry.
• To identify any spectral heterogeneity among multiple vials from the same manufacturing batch.
• To evaluate the manufacturing process control for acetazolamide.

Main Methods:

• Fourier Transform Near-Infrared (FT-NIR) spectrometry was employed to analyze 12 vials of Acetazolamide 500 mg.
• Statistical methods including Bootstrap Error-Adjusted Single-sample Technique (BEST) and Principal Component Analysis (PCA) were utilized.
• Spectral data in the 4200-5200 cm^-1 range were analyzed for heterogeneity.

Main Results:

• Significant spectral heterogeneity was detected among the analyzed acetazolamide vials.
• Vial 6 was identified as a statistical outlier, showing a distinct absorbance peak at 4851 cm^-1.
• This outlier was positioned 4.03 standard deviations from the lot cluster, indicating deviation from the norm.

Conclusions:

• The observed spectral heterogeneity suggests the manufacturing process may have operated outside of process control.
• Quality assurance screenings using techniques like FT-NIR are critical for supply chain transparency.
• Reliable medication is essential, particularly given current national shortages of acetazolamide.