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Current Pharmaceutical Analysis

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ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

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Research Article

Study of Intrinsic Stability of Mometasone Furoate in Presence of Salicylic Acid by HPTLC and Characterization, Cytotoxicity Testing of Major Degradation Product of Mometasone Furoate

Author(s): Vijaya Vichare*, Vishnu P. Choudhari and M. Venkata Reddy

Volume 15, Issue 6, 2019

Page: [592 - 603] Pages: 12

DOI: 10.2174/1573412914666180418162143

Price: $65

Abstract

Background: A successful attempt has been done to develop and validate a simple stability indicating HPTLC method for the estimation of Mometasone furoate (MF) and its degradation product in the presence of Salicylic acid (SA). The degradation product was isolated, characterized and tested for cytotoxicity.

Introduction: Mometasone furoate (MF) is chemically 9,21-Dichloro-17α-[(2-furanylcarbonyl) oxy]- 11β-hydroxy-16-α-methylpregna-1,4-diene-3,20-dione, a high potency glucocorticoid. Salicylic acid (SA) has antiseptic, antifungal and keratolytic properties. Combination of MF and SA is available in the market as an ointment and is used for the treatment of skin inflammation, skin diseases, acne, skin redness and other conditions. Till now, there is no scientific documentation on HPTLC method for simultaneous estimation of MF and SA in the topical formulation; stress testing of drugs and determination of degradation products.

Methods: Combination of Toluene: Ethyl Acetate: Methanol: Ammonia (6.4:1.5:2.0:0.1) was selected as the mobile phase. Detection was done by UV absorbance mode at wavelength 250 nm. Topical formulation containing MF and SA was analyzed by the developed method. The developed method was validated as per ICH guidelines. The standard drugs were subjected to stress testing like hydrolysis, oxidative, thermal and photolytic degradation.

Results: Good separation with Rf values 0.61 ± 0.02 (MF) and 0.21 ± 0.02 (SA) was achieved by optimized chromatographic conditions. The % drug content was found to be 97.41±1.15 and 99.43 ± 0.73 for MF and SA, respectively in a topical formulation. From the results of validation parameters, the developed method was found to be specific, accurate, precise, sensitive and robust. After stress testing, SA was found to be stable under different stress conditions. Whereas, MF was found to be base sensitive and single degradation product was observed and isolated by preparative TLC. It was characterized by LC-MS and LC-MS/MS studies. Isolated degradation product was subjected to cytotoxicity testing on A549 and SiHa cell lines.

Conclusion: A simple stability indicating HPTLC method was developed and validated for the estimation of MF and its degradation product in presence of SA. Probable structure of degradation product of MF and probable pathway of degradation was interpreted. Results of cytotoxicity testing showed that the degradation product was more cytotoxic as compared to MF against both the cell lines.

Keywords: Mometasone furoate, salicylic acid, HPTLC, cytotoxicity testing, LC-MS, stress testing.

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[1]
Block, J.H.; Beale, J.M. Wilson and Gisvold’s textbook of Organic Medicinal and Pharmaceutical Chemistry, 11th ed, Lippincott Williams and Wilkins; , 2004, pp. 233-234, 813.
[2]
Tripathi, K.D. Essentials of Medical Pharmacology, 7th ed; Jaypee Brothers Medical Publishers, 2014, pp. 889-, 895-896.
[3]
Indian Pharmacopoeia, Government of India, Ministry of Health and family welfare; Published by Indian Pharmacopoeia Commission, Gaziabad 2014, Vol. II, 2243-2244. Vol. III, pp. 2705- 2706.
[4]
British Pharmacopoeia, The Stationary Office on behalf of Medicines and Health Care Products Regulatory Agency (MHRA), London, United Kingdom 2008, Vol. II, 1485-1486. 1920-1922
[5]
United States. Pharmacopoeia-34 National Formulary-29; United States Pharmacopoeial Convection: Rockville, 2011, Vol. III, pp. 3550-3551, 4194-4195.
[6]
Parmar, A.P.; Maheshwari, D.G. Simultaneous estimation of mupirocin and mometasone furoate in pharmaceutical dosage form by q-absorption ratio method. Int. Res. J. Pharm. App. Sci., 2015, 5(2), 1-7.
[7]
Zanwar, A.S.; Sen, D.B.; Ruikar, R.B.; Seth, A.K. Spectroscopic methods for the simultaneous estimation of mometasone furoate and formoterol fumarate in rotacaps. Indo Am. J. Pharmaceut. Res., 2014, 4(12), 5928-5933.
[8]
Patel, H.D.; Patel, M.M. Development and validation of UV spectrophotometric method for simultaneous estimation of terbinafine hydrochloride and mometasone furoate in combined dosage form. Asian J. Res. Chem, 2013, 6(1), 29-34.
[9]
Bhangale, P.R.; Jain, H.K. Spectrophotometric method for simultaneous estimation of formoterol fumarate and mometasone furoate in respicaps. Int. Res. J. Pharm, 2013, 4(6), 220-223.
[10]
Vanani, D.R.; Desai, S.D.; Patel, K.G.; Shah, P.A. Application of ratio derivative spectrophotometry for simultaneous determination of mometasone furoate and salicylic acid in semisolid dosage form. Int. J. Anal. Bioanal. Chem., 2013, 3(3), 67-71.
[11]
Vichare, V.S.; Choudhari, V.P.; Reddy, M.V. Simultaneous estimation of mometasone furoate and salicylic acid in topical formulation by UV-visible spectrophotometry. Int. J. Chem. Sci., 2017, 15(2), 129.
[12]
Shaikh, K.A.; Patil, A.T. Stability-indicating HPLC method for the determination of mometasone furoate, oxymetazoline, phenyl ethanol and benzalkonium chloride in nasal spray solution. J. Food Drug Anal., 2013, 1, 14-21.
[13]
Modi, P.B.; Shah, N.J. DoE approach: A stability indicating RP-HPLC method for simultaneous estimation of methylparaben, mometasone furoate and eberconazole nitrate in topical formulations. J. Appl. Pharm. Sci., 2014, 4(12), 20-25.
[14]
Sharma, N.; Rao, S.; Vaghela, B. Validated stability-indicating high-performance liquid chromatographic method for estimation of degradation behaviour of eberconazole nitrate and mometasone furoate in cream formulation. Indian J. Pharm. Sci., 2013, 75(1), 76-82.
[15]
Jain, H.K.; Bhangale, P.R.; Satam, S.S. Stability indicating LC method for estimation of Formoterol fumarate and Mometasone furoate in respicaps dosage form. Indian J. Chem. Technol., 2016, 23(5), 405-411.
[16]
Merey, H.A.; El-Mosallamy, S.S.; Hassan, N.Y.; El-Zeany, B.A. Validated chromatographic methods for the simultaneous determination of Mometasone furoate and Formoterol fumarate dihydrate in a combined dosage form. B-FOPCU, 2016, 54(1), 99-106.
[17]
El-Bagary, R.I.; Fouad, M.A.; El-Shal, M.A.; Tolba, E.H. Forced degradation of Mometasone furoate and development of two RP-HPLC methods for its determination with Formoterol fumarate or salicylic acid. Arab. J. Chem., 2016, 9(3), 493-505.
[18]
Choudhari, V.P.; Phadtare, S.; Gaikwad, H.; Salunkhe, R.; Galange, A. Development and validation of RP-HPLC-PDA method for estimation of mometasone furoate, salicylic acid, methyl paraben and propyl paraben in combined topical formulation by using design of experiment. Research & Reviews: Journal of Pharmaceutical Quality Assurance, 2015, 1(1), 38-48.
[19]
Youssef, R.M.; Korany, M.A.; Afify, M.A. Development of a stability indicating HPLC-DAD method for the simultaneous determination of mometsone furoate and salicylic acid in an ointment matrix. Anal. Methods, 2014, 6(10), 3410-3419.
[20]
Sahasranaman, S.; Issar, M.; Tóth, G.; Horváth, G.; Hochhaus, G. Characterization of degradation products of mometasone furoate. Die Pharmazie - An International. Journal of Pharmaceutical Sciences,, 2004, 59(5), 367-373.
[21]
Sahasranaman, S.; Issar, M.; Hochhaus, G. Metabolism of mometasone furoate and biological activity of the metabolites. Drug Metab. Dispos., 2006, 34(2), 225-233.
[22]
ICH Harmonised Tripartite Guideline, Validation of Analytical Procedures: Text And Methodology Q2(R1), November 2005.
[23]
ICH Harmonised Tripartite Guideline, ICH Stability Testing: Photostability Testing of New Drug Substances and Products Q1B, November 1996.
[24]
ICH Harmonised Tripartite Guideline, Stability Testing of New Drug Substances and Products Q1A(R2), February 2003.
[25]
Singh, S.; Bakshi, M. Guidance on conduct of stress tests to determine inherent stability of drugs. Pharm. Technol., 2000, 24, 1-14.
[26]
Bakshi, M.; Singh, S. Development of validated stability-indicating assay methods-critical review. J. Pharm. Biomed. Anal., 2002, 28(6), 1011-1040.
[27]
Fernanda, C.S.; Luciana, C.B.; Rogerio, C.; Rilton, A.F.; Tania, M.B. HPLC Stability indicating assay method for metformin hydrochloride in bulk drug and tablets and cytotoxicity of degradation products. Curr. Pharm. Anal., 2012, 8(4), 368-374.
[28]
Vichai, V.; Kirtikara, K. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat. Protoc., 2006, 1, 1112-1116.
[29]
Alini, D.C.; Franciele, T.G.; Carolina, C.P.; Vitor, T.; Nadia, M.V.; Elfrides, E.S. Stability-Indicating LC assay with determination of system suitability limits by a robustness test for sitagliptin in tablets and assessment of cytotoxicity for degradation products. Curr. Pharm. Anal., 2012, 8(4), 360-367.
[30]
Skehn, P.; Storeng, R.; Scudiero, A.; Monks, J.; McMohan, D.; Vistica, D. New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst., 1990, 82(13), 1107-1112.
[31]
Chavan, R.; Khan, M.; Sathe, N.; Mankar, N.A.A. Review: SRB assay for screening anticancer activity of herbal drugs (in vitro). Int. Ayurvedic Med. J., 2016, 4(2), 66-70.

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