Rapid Quality Screening of Intra-lot and Inter-lot Variability of Pentamidine Isethionate Using Near-Infrared Spectrometry

Pentamidine for Injection, USP is a sterile, lyophilized antimicrobial agent supplied as a white to off-white powder in vials containing 300 mg for intravenous administration. The product is reconstituted with sterile water for injection prior to administration, yielding a clear, colorless to slightly yellow solution.Variability was detected both within a lot (where one vial from 8 vials was 18.4 SDs from the center of the cluster) and between lots of the drug, where spectra occupied distinct regions of hyperspace. Subcluster analysis confirmed statistically significant separation between lots (rtn = 0.9635, rts = 0.8898, p = 0.02). These results were derived using statistical analyses of the spectra that included principal component analysis (PCA) and the Bootstrap Error-Adjusted Single-sample Technique (BEST).The variability detected suggests that pentamidine may have been manufactured while the production process was operating outside of a state of process control. These findings also highlight the utility of FT-NIR spectrometry in rapidly screening pharmaceutical products for quality.