Validated Stability-Indicating Method Development Designed for the Determination of Metronidazole in the Presence of Povidone-Iodine in Dermatological Formulation by a First-Order Derivative UV Spectrophotometric Method

Metronidazole, a nitroimidazole antimicrobial, is used in combination with povidone iodine in the form of a topical ointment for treating and preventing skin infections in several skin conditions such as otitis externa, sycosis barbae, tinea infestations, cutaneous candidosis, burns, boils, or ulcers. The study presented is aimed at developing a stability-indicating method for the determination of metronidazole in the presence of povidone-iodine in dermatological formulations by a first-order derivative UV spectrophotometric method that provides an enhanced resolution of overlapping spectra. The λ_max was found at 319 nm for metronidazole and at 235 nm for povidone-iodine. First-order detection wavelength has been taken at 298 and 221 nm for metronidazole and povidone-iodine, respectively. Beer’s law was obeyed in a concentration range of 5–45 µg/mL with R² values of metronidazole and povidone of 0.999 and 0.9967, respectively, using distilled water as an economical solvent. The developed method was validated on various parameters such as accuracy, precision, robustness, limit of quantification and limit of detection. It can be perceived from the results that a minimum intraday and interday variation limiting below 2% of relative standard deviation was established. The percentage recovery using the stated method was worthy of characteristics with its label claim and found within the range 100.22–101%, within the acceptable limits of International Conference on Harmonization guidelines for the forced degradation and establishes a validated method for metronidazole and povidone-iodine and its main degradants in the active pharmaceutical ingredients (API) and the marketed formulations. The exclusivity of the presented first-order derivative UV spectroscopic method lies in it being simple, economical, safe, precise, accurate, and reproducible for future studies of the prediction of stability of the drugs in the marketed formulation. The technique is established to be unambiguous for the determination of a drug and its degradants.

1. S. Pandey, R. Pandey, S. S. Shukla, Indian J. Pharm. Ed. Res., 55, No. 1, 249-255 (2021).

2. A. Parmar, S. Sharma, TrAC Trends Anal. Chem., 77, 44-53 (2016)

3. British Pharmacopoeia, British Pharmacopoeia Commission, Monograph, 0675 (2007).

4. K. D. Tripathi. Antiprotozoal Drugs. Essentials of Pharmacology, 5th ed., 750-753 (2003).

5. A. Lorenzo, M. E. Mothe, C. Sanz, Huidobro N. Ruiz, A. Diambra, M. I. Ribo et al., Pak. J. Soc. Sci., 4, No. 1, 82-104 (2007).

6. G. Mary, N. Balasubrahmanian, K. S. Nagaraja, Chem. Pharm. Bull. (Tokyo), 56, No. 7, 888-893 (2008).

7. M. P. Arena, M. D. Porter, J. S. Fritz, Anal. Chem., 74, No. 1, 185-190 (2002).

8. P. Tavlarakis, J. J. Urban, N. Snow, J. Chromatogr. Sci., 49, No. 6, 457-462 (2011).

9. A. M. Frasey, B. G. Anne, M. P. Pouget, M. Vennat, B. Lartigue, C. Galmier, Micro Acta, 144, 171-176 (2004).

10. C. Akay, S. A. Ozkan, Z. Senturk, S. Cevheroglu, Farmaco, 57, No. 11, 953-957 (2003).

11. M. F. Rizk, F. Ibrahim Belal, S. Ahmed, Z. A. Shebribah, J. Pharm. Biomed. Anal., 27, No. 5, 813-820 (2002).

12. S. Bollo, L. J. Nunez-Vergara, J. A. Squella, J. Elec. Chem., 562, No. 1, 9-14 (2004).

13. M. L. Loke, J. Fornelund, B. Halling Sorensen, Chemosphere, 48, 351 (2004).

14. V. Ellenrieder, W. Boeck, C. Richer, R. Marre, G. Adler, B. Glasbrenner, Scan. J. Gas., 34, 750 (1999).

15. P. Nagaraja, K. R. Sunitha, R. A. Vasantha, H. S. Yathirajan, J. Pharm. Biomed. Anal., 28, 527-535 (2002).

16. P. Parimoo, C. V. N. Prasad, A. Gautam, Int. J. Pharm., 134, No. 22, 231-234 (1996).

17. P. Parimoo, C. V. N. Prasad, R. Vineeth, J. Pharm. Biomed. Anal., 14, 389-393 (1996).

18. H. Chen, Z. Gong, Z. Zhang, J. Pharm. Biomed. Anal., 41, 1412-1417 (2006).

19. T. Karuna, K. Neelima, G. Venkateshwarlu, P. Y. Swamy, J. Sci. Ind. Res., 65, 808-811 (2006).