Simultaneous determination of mometasone furoate and calcipotriol in a binary mixture by validated HPLC and chemometric-assisted UV spectrophotometric methods and identification of degradation products by LC-MS

Document Type : Original Article

Authors

1 Department of Pharmaceutical Control, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran

4 Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

5 Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

6 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): A new binary mixture containing mometasone furoate (MF) and calcipotriol (CP) is suggested to manage psoriasis; since the combined stability profile of these drugs is poorly understood.
Materials and Methods: Herein MF, CP, and their mixtures were subjected to various stress conditions. Also, stability-indicating HPLC was developed and validated according to ICH guidelines with Box-Behnken design. The degradation products (DPs) were predicted in silico and identified using LC-MS. The bioactivity and toxicity of DPs were studied using molecular docking and alamarBlue assay, respectively. Spectroscopic techniques of the first derivative, first-derivative ratio, and the mean-centering of ratio spectra were also used to determine MF and CP in the mixture because of spectra overlapping. 
Results: The major degradants for MF in alkaline conditions were DP1, DP2, and DP3, while in thermal and UV conditions, only DP1 was generated. CP gave one degradant in all conditions. No new impurity was observed in the MF and CP mixtures. The results of spectrophotometry showed good linearity in the range of 4-50 and 2-20 µg/ml, while linearity for HPLC was in the range of 4–50 and 0.5–2.5 µg/ml for MF and CP, respectively. Recovery was 99.61–100.38% for UV and 100.4% for HPLC methods of MF and 100.6–101.4% for UV and 99.5% for HPLC methods of CP.
Conclusion: The developed methods can be used as simple, accurate, precise, and rapid techniques for routine quality control of MF and CP mixtures.

Keywords

References

1. Semenov YR, Herbosa CM, Rogers AT, Huang A, Kwatra SG, Cohen B, et al. Psoriasis and mortality in the US: Data from the national health and nutrition examination survey. J Am Acad Dermatol 2021; 85:396-403. 
2. An L, Li J, Liu B, Hui J, Zhang Q, Zhang X, et al. Knockdown of TRPM7 attenuates apoptosis and inflammation in neonatal necrotizing enterocolitis model cell IEC-6 via modulating TLR4/NF-κB and MEK/ERK pathways. Iranian IJBMS 2022; 25: 947-953.
3.Aslankoc R, Savran M, Doğuç DK, Sevimli M, Tekin H, Kaynak M. Ameliorating effects of ramelteon on oxidative stress, inflammation, apoptosis, and autophagy markers in methotrexate-induced cerebral toxicity. IJBMS 2022; 25: 1183-1189.
4. Lawton S. Psoriasis presentations and potential treatment pathways. Practice Nursing 2018; 29:517-520.
5. Gual A, Pau-Charles I, Molin S. Topical treatment for scalp psoriasis: Comparison of patient preference, quality of life and efficacy for non-alcoholic mometasone emulsion versus calcipotriol/betamethasone gel in daily clinical practice. J Dermatol Treat 2016; 27:228-234.
6. Elmets CA, Korman NJ, Prater EF, Wong EB, Rupani RN, Kivelevitch D, et al. Joint AAD–NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures. J Am Acad Dermatol 2021; 84:432-470.
7. Kleyn EC, Morsman E, Griffin L, Wu JJ, Cm van de Kerkhof P, Gulliver W, et al. Review of international psoriasis guidelines for the treatment of psoriasis: Recommendations for topical corticosteroid treatments. J Dermatol Treat 2019; 30:311-319.
8. Ma L, Yang Q, Yang H, Wang G, Zheng M, Hao F, et al. Calcipotriol plus betamethasone dipropionate gel compared with calcipotriol scalp solution in the treatment of scalp psoriasis: A randomized, controlled trial investigating efficacy and safety in a Chinese population. Int J Dermatol 2016; 55:106-113.
9. McCormack PL. Calcipotriol/betamethasone dipropionate. Drugs 2011; 71: 709-730.
10. Svensson Å, Reidhav I, Gisslén H, Nordin P, Giös I. A comparative study of mometasone furoate ointment and betamethasone valerate ointment in patients with psoriasis vulgaris. Curr Ther Res 1992; 52:390-396. 
11. Corazza M, Virgili A, Toni G, Borghi A. Mometasone furoate in the treatment of vulvar lichen sclerosus: Could its formulation influence efficacy, tolerability and adherence to treatment? J Dermatol Treat 2018; 29:305-309.
12. Shinde G, Desai P, Shelke S, Patel R, Bangale G, Kulkarni D. Mometasone furoate-loaded aspasomal gel for topical treatment of psoriasis: formulation, optimization, in vitro and in vivo performance. J Dermatol Treat 2020:1-12.
13. FDA/ICH. Guidance for industry. Q8 Pharmaceutical development. 2006.
14. Xu Q. Advancing USP compendial methods for fixed dose combinations: A case study of metoprolol tartrate and hydrochlorothiazide tablets. J Pharm Anal 2019; 9:77-82.
15. Davoodi J, Majidi S, Jahani M, Tayarani‐najaran Z, Golmohammadzadeh S, Kamali H. Implementation of design of experiments for optimization of forced degradation conditions and development of a stability‐indicating HPLC method for sepiwhite. J Sep Sci 2021; 44: 4299-4312.
16. Jahani M, Fazly Bazzaz BS, Akaberi M, Rajabi O, Hadizadeh F. Recent Progresses in analytical perspectives of degradation studies and impurity profiling in pharmaceutical developments: An updated review. Crit Rev Anal Chem 2021:1-22.
17. Tome T, Žigart N, Časar Z, Obreza A. Development and optimization of liquid chromatography analytical methods by using AQbD principles: Overview and recent advances. Org Process Res Dev 2019; 23:1784-1802.
18. El-Sayed HM, Hashem H. Quality by design strategy for simultaneous HPLC determination of bromhexine HCl and its metabolite ambroxol HCl in dosage forms and plasma. Chromatographia 2020; 83:1075-1085.
19. Panchale WA, Bakal RL. First-order derivative spectrophotometric estimation of gemifloxacin mesylate and ambroxol HCl in tablet dosage form. GSC Biol Pharm Sci 2021; 14: 29-36.
20. Victor N, Elfiky H, Badawey A, Abdelghany M. Simultaneous determination of xipamide and triamterene by first derivative, ratio difference, and derivative ratio spectrophotometric methods. Arch Pharm Sci Ain Shams univ 2021; 5:52-62.
21. Essam HM, Saad MN, Elzanfaly ES, Amer SM. Optimization and validation of eco-friendly RP-HPLC and univariate spectrophotometric methods for the simultaneous determination of fluorometholone and tetrahydrozoline hydrochloride. Acta Chromatogr 2021; 33:216-227.
22. Lotfy HM, Salem H, Abdelkawy M, Samir A. Spectrophotometric methods for simultaneous determination of betamethasone valerate and fusidic acid in their binary mixture. Spectrochim Acta A Mol Biomol Spectrosc 2015; 140:294-304.
23. Teng XW, Cutler DC, Davies NM. Degradation kinetics of mometasone furoate in aqueous systems. Int J Pharm 2003; 259:129-141.
24. Sahasranaman S, Tang Y, Biniasz D, Hochhaus G. A sensitive liquid chromatography–tandem mass spectrometry method for the quantification of mometasone furoate in human plasma. J Chromatogr B 2005; 819:175-179.
25. Teng XW, Foe K, Brown KF, Cutler DJ, Davies NM. High-performance liquid chromatographic analysis of mometasone furoate and its degradation products: Application to in vitro degradation studies. J Pharm Biomed Anal 2001; 26:313-319.
26. Ramzia I, Marwa A, Manal A, Enas H. Derivative, derivative of the ratio spectrophotometric and stability-indicating RP–HPLC methods for the determination of mometasone furoate and miconazole nitrate in cream. J Chem Pharm Res 2013; 5:368.
27. Shaikh KA, Patil AT. Stability-indicating HPLC method for the determination of mometazone furoate, oxymetazoline, phenyl ethanol and benzalkonium chloride in nasal spray solution. J Trace Anal Food & Drugs 2013; 1:14-21.
28. Shaikh S, Muneera M, Thusleem O, Tahir M, Kondaguli AV. A simple RP-HPLC method for the simultaneous quantitation of chlorocresol, mometasone furoate, and fusidic acid in creams. J Chromatogr Sci 2009; 47:178-183.
29. Roy C, Chakrabarty J. Stability-indicating validated novel RP-HPLC method for simultaneous estimation of methylparaben, ketoconazole, and mometasone furoate in topical pharmaceutical dosage formulation. Int Sch Res Notices 2013; 342794.
30. Singh M, Charde R, Charde MM. Determination of Calcipotriene, its forced degradation and impurity analysis by HPLC. Int J Pharm Life Sci 2015; 6: 4631-4641.
31. Roy C, Chakrabarty J, Ratti RR. Development and validation of a stability-indicating NP-HPLC method for simultaneous determination of betamethasone dipropionate and calcipotriene in topical dosage form. Appl Sci Res 2013; 5:15-24.
32. Badilli U, Amasya G, Özkan S, Tarimci N. Simultaneous determination of clobetasol propionate and calcipotriol in a novel fixed dose emulgel formulation by LC-UV. Chromatographia 2013; 76:133-140.
33. Ayers PW, Parr RG. Variational principles for describing chemical reactions: the Fukui function and chemical hardness revisited. J Am Chem Soc 2000; 122:2010-2018.
34. Rignall A. ICHQ1A (R2) stability testing of new drug substance and product and ICHQ1C stability testing of new dosage forms. ICH quality guidelines: an implementation guide. 2017; 3: 214-220.
35. Mohamed EH, Lotfy HM, Hegazy MA, Mowaka S. Different applications of isosbestic points, normalized spectra and dual wavelength as powerful tools for resolution of multicomponent mixtures with severely overlapping spectra. Chem Cent J 2017; 11:1-15.
36. Ganorkar A, Gupta K. Analytical Quality by Design: A mini review. Biomed J Sci Tech Res 2017; 1:1555-8.
37. Guideline ICH. Validation of analytical procedures: Text and Methodology. Q2 (R1). 2005; 1:05.
38. Kumar P, Nagarajan A, Uchil PD. Analysis of cell viability by the alamarBlue assay. Cold Spring Harbor Protocols 2018; pdb. prot095489.
39. Salinas F, Nevado JB, Mansilla AE. A new spectrophotometric method for quantitative multicomponent analysis resolution of mixtures of salicylic and salicyluric acids. Talanta 1990; 37:347-351. 
40. Sahasranaman S, Issar M, Toth G, Horváth G, Hochhaus G. Characterization of degradation products of mometasone furoate. Die Pharmazie-An Inter J Pharm Sci 2004; 59:367-373.
41. Vichare V, Choudhari VP, Reddy MV. 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. Curr Pharm Anal 2019; 15:592-603.
42. Iqbal J, Gupta A, Husain A. Photochemistry of clobetasol propionate, a steroidal anti-inflammatory drug. Arkivoc 2006; 11:91-98.
43. Simonsen L, Høy G, Didriksen E, Persson J, Melchior N, Hansen J. Development of a new formulation combining calcipotriol and betamethasone dipropionate in an ointment vehicle. Drug Dev Ind Pharm 2004; 30:1095-1102.
44. Li X, Wang J, Li G, Lin C, Zhang X, Sun Y, et al. Evaluation of calcipotriol transdermal permeation through pig, rat and mouse skin using liquid chromatography–tandem mass spectrometry. Biomed Chromatogr 2013; 27:1714-1719.
45. Napoli JL, Koszewski NJ, Horst RL. (14) Isolation and identification of vitamin D metabolites. Meth Enzymol 1986; 123:127-140.
46. Harvey D. Modern analytical chemistry: McGraw-Hill New York; 2000.
47. Mahmoodani F, Perera CO, Fedrizzi B, Abernethy G, Chen H. Degradation studies of cholecalciferol (vitamin D3) using HPLC-DAD, UHPLC-MS/MS and chemical derivatization. Food chemistry 2017; 219:373-381.
48. Bundgaard H, Hansen J. Studies on the stability of corticosteroids VI. Kinetics of the rearrangement of betamethasone-17-valerate to the 21-valerate ester in aqueous solution. Int. J. Pharm. 1981; 7:197-203.
49. Foe K, Cheung HA, Tattam BN, Brown KF, Seale JP. Degradation products of beclomethasone dipropionate in human plasma. Drug metabolism and disposition 1998; 26:132-137.
50. Yip Y, Po ALW, Irwin W. Kinetics of decomposition and formulation of hydrocortisone butyrate in semiaqueous and gel systems. J Pharm Sci 1983; 72:776-781.
51. Mori M, Pimpinelli N, Giannotti B. Topical corticosteroids and unwanted local effects. Drug safety 1994; 10:406-412.
52. Zhang F, Nunes M, Segmuller B, Dunphy R, Hesse RH, Setty SKS. Degradation chemistry of a Vitamin D analogue (ecalcidene) investigated by HPLC–MS, HPLC–NMR and chemical derivatization. J Pharm Biomed Anal 2006; 40:850-863.
53. Bhogadi R, Satyanarayana A, Rao NS, Arutla S, Reddy AM. Stability indicating RP-HPLC method for estimation of impurities of vitamin D 3 analogue and corticosteroid used as antipsoriatic drugs. An attempt to characterize pre-calcipotriene. Am J Analyt Chem 2015; 6:1050-1058.
Iranian Journal of Basic Medical Sciences
Volume 26, Issue 1
January 2023
Pages 37-47

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