Characterization of the degradation of dipyrone (metamizole) in expired oral pharmaceutical products by Raman spectroscopy and principal component analysis (PCA)

Abstract

Stability studies are essential to ensure that a drug maintains its qualities after leaving the production line until the end of the validity date. This study aimed to identify the alterations related to shelf time in commercial formulations containing dipyrone (metamizole) and to model the shelf time by Raman spectroscopy (830 nm, 350 mW). Spectra of nine commercial medicines containing dipyrone sodium were obtained during the validity period (valid samples) and after the expiration date (overdue samples) with shelf times ranging from 46 to 62 months. The spectra were compared to identify changes due to the dipyrone degradation and develop a model to estimate the shelf time. The Raman analysis of valid and overdue samples showed peaks due to the hydrolysis-oxidation of dipyrone: a blue-shift (N feature in the difference spectrum) of the bands assigned to aromatic and pyrazole rings due to the presence of the metabolite N-methylaminoantipyrine, a decrease in peaks related to the dissociation of − SO₃Na due to the hydrolysis/oxidation, and an increase in peaks associated with sodium sulfate/disulfate. A regression model based upon principal component analysis (PCA) showed a strong correlation between shelf time and the PCA variable PC2 (Pearson’s correlation coefficient r = 0.804). The study showed the feasibility of Raman spectroscopy in identifying the degradation of dipyrone sodium to characterize the shelf time and use in the quality control of commercial medicines.

Keywords:

• Degradation
• dipyrone sodium
• metamizole
• principal component analysis (PCA)
• Raman spectroscopy
• shelf-life

Acknowledgments

L. Silveira Jr. and M. T. T. Pacheco acknowledge Ânima Institute (AI) for the research fellowships.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

L. Silveira Jr. acknowledges FAPESP (São Paulo Research Foundation) for granting the Raman spectrometer (Process No. 2009/01788-5) and CNPq (Brazilian National Council for Scientific and Technological Development) for the productivity fellowship (Process No. 306344/2017-3).