Home >Current Issue
Volume: 9, Issue: 8, August, 2019
Identification and quantitation of related substances of super potent steroid in its topical combination drug product with vitamin D3 analogueAuthor Affiliations
Clobetasol propionate is an internationally accepted common name for 21-chloro-9-fluoro-11beta,17-dihydroxy- 16beta-methylpregna-1,4-diene-3,20-dione 17-propionate. The combination of calcipotriol (vitamin D3 analogue) and clobetasol propionate (super potent steroid) is being used as a topical formulation for the treatment of psoriasis from several years. In this work, an ultra-high performance liquid chromatography equipped with photodiode array detector and a mass compatible mobile phase in a gradient elution is employed for the separation of five related substances in presence of calcipotriol and its two impurities with a last eluting impurity in less than 11 minutes. A simple and efficient sample extraction procedure was developed to achieve the highest sensitivity as of today with limit of detection and limit of quantitation of 0.03% and 0.10%, respectively, as required by industry for drug product of clobetasol propionate and its combination products. Stationary phase with fused core particle technology is employed for the separation of impurities. Precision of the method is found to be less than 1.0% Relative standard deviation (RSD). The correlation coefficient is >0.999. Accuracy of method is ranged from 93.3% to 108.0%. This is the first reported Ultra high performance liquid chromatography (UHPLC) method for the estimation of five related substances of clobetasol propionate in its combination product with calcipotriol.
Copyright: The Author(s). This is an open access article distributed under the Creative Commons Attribution Non-Commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Amr MB, Abd El-aziz BA, Abd El-Alim, Ahmed SS. Stability-indicating spectro-photometric methods for determination of Clobetasol propionate in the presence of its alkaline degradation product by derivative spectrophotometric techniques. Drug Test Anal, 2010; 2: 130-6.
Angelo T, Cunha-Filho MS, Gelfuso GM, Gratieri T. Chromatographic method for clobetasol propionate determination in hair follicles and in different skin layers. Biomed Chromatogr, 2017; 31(2):1-7. https://doi.org/10.1002/bmc.3804
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; 76:133-40. https://doi.org/10.1007/s10337-012-2380-8
Bassuoni YF, Elzanfaly ES, Essam HM, Zaazaa HE. Development and validation of stability indicating TLC densitometric and spectrophotometric methods for determination of Clobetasol propionate. Bull Fac Pharm Cairo Univ, 2016; 54:165-74. https://doi.org/10.1016/j.bfopcu.2016.05.001
Bhuyian M, Rashid DH, Islam A, Tareque M. Development and validation of method for determination of clobetasol propionate and salicylic acid from pharmaceutical dosage form by HPLC. Br J Pharm Res, 2015; 7:375-85. https://doi.org/10.9734/BJPR/2015/18494
Fauzee AF, Walker RB. Forced degradation studies of clobetasol 17-propionate in methanol, propylene glycol, as bulk drug and cream formulations by RP-HPLC. J Sep Sci, 2013; 36:849-56. https://doi.org/10.1002/jssc.201200969
FDA. Available via https://www.fda.gov/downloads/Drugs/ Guidances/UCM386366.pdf (Accessed 26 February 2019).
Fontana MC, Bastos MO, Beck R. Development and validation of a fast RP-HPLC method for the determination of clobetasol propionate in topical nanocapsule suspensions. J Chromatogr Sci, 2010; 48:637-40. https://doi.org/10.1093/chromsci/48.8.637
Gagliardi L, De Orsi D, Manna F, Tonelli D. HPLC determination of clobetasol propionate in cosmetic products. J Liq Chromatogr Relat Technol, 2000; 23:355-62. https://doi.org/10.1081/JLC-100101456
Gordon ML. The role of clobetasol propionate emollient 0.05% in the treatment of patients with dry, scaly, corticosteroid-responsive dermatoses. J Clin Ther, 1988; 20:26-38. https://doi.org/10.1016/S0149-2918(98)80032-5
Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet, 2007; 370:263-71. https://doi.org/10.1016/S0140-6736(07)61128-3
ICH. Available via https://www.ich.org/fileadmin/Public_Web_ Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline. pdf (Accessed 26 February 2019).
Joseph JK, Stephanie AS, William LJ, Barry EB. Fused-core particle technology in high-performance liquid chromatography: an overview. J Pharm Anal, 2013; 3:303-12. https://doi.org/10.1016/j.jpha.2013.02.005
Manoharan G. Development and validation of a stability-indicating RP-HPLC method for the estimation of clobetasol propionate in bulk and ointment dosage form. Eur J Pharm Med Res, 2017; 4:119-26.
Marika K, Katherine F, Jianmin L, Mike CG, Debra F. A sensitive high-throughput HPLC assay for simultaneous determination of everolimus and clobetasol propionate. J Chromatogr Sci, 2008; 46:23-9. https://doi.org/10.1093/chromsci/46.1.23
Michael ES. UPLC: an introduction and review. J Liq Chromatogr Relat Technol, 2005; 28:1253-63. https://doi.org/10.1081/JLC-200053046
Mostafa AA, Bebawy LI, Refaat HH. Spectrophotometric determination of clobetasol propionate, halobetasol propionate, quinagolide hydrochloride, through charge transfer complexation. J Pharm Biomed Anal, 2002; 27:889-99. https://doi.org/10.1016/S0731-7085(01)00581-7
Mrunali RP, Rashmin BP, Jolly RP, Bharat GP. HPTLC method for estimation of Clobetasol propionate in topical gel formulations and in vitro study. Anal Methods, 2010; 2:275-81. https://doi.org/10.1039/b9ay00240e
Nam YS, Kwon IK, Lee KB. Monitoring of clobetasol propionate and betamethasone dipropionate as undeclared steroids in cosmetic products manufactured in Korea. Forensic Sci Int, 2011; 210:144-8. https://doi.org/10.1016/j.forsciint.2011.02.027
Neelam D, Sunil K, Sunny R, Jagbir G , Sheefali M, Rekha R. Development and validation of UV spectrophotometric method for quantitative estimation of clobetasol 17-propionate. Asian J Chem Pharm Sci, 2016; 1:36-40 https://doi.org/10.18311/ajcps/2016/7726
Nidhi P, Pooja P, Dhananjay M. Development and validation for RP-HPLC method simultaneous estimation of nadifloxacin and clobetasol propionate in its pharmaceutical dosage form. Am J PharmTech Res, 2016; 6(5):289-304.
Reepmeyer JC, Revelle LK, Vidavsky I. Detection of clobetasol propionate as an undeclared steroid in zinc pyrithione formulations by high-performance liquid chromatography with rapid-scanning ultraviolet spectroscopy and mass spectrometry. J Chromatogr A, 1998; 828:239-46. https://doi.org/10.1016/S0021-9673(98)00786-9
Sparidans RW, van Velsen SGA, de Roos MP, Schellens JHM, Bruijnzeel-Koomen CA, Beijnen JH. Liquid chromatography-tandem mass spectrometric assay for clobetasol propionate in human serum from patients with atopic dermatitis. J Chromatogr B, 2010; 878:2150-4. https://doi.org/10.1016/j.jchromb.2010.06.011
Turabi ZM, Khatatbeh OA. Simultaneous determination of clobetasol (as propionate) and chlorocresol in cream by stability indicating RP-HPLC method. Int J Pharm Sci Drug Res, 2014; 6:140-4.
Van Velsen SGA, De Roos MP, Haeck IM, Sparidans RW, Bruijnzeel-Koomen CA. The potency of clobetasol propionate: Serum levels of clobetasol propionate and adrenal function during therapy with 0.05% clobetasol propionate in patients with severe atopic dermatitis. J Dermatol Treat, 2012; 23:16-20. https://doi.org/10.3109/09546634.2010.534127
Wenling Y, Xiaomei Y, Fanghua S, Zhigang L, Yongkun L, Liangzhong Y, Ruixun W, Qing L, Kaishun B. Qualitative and quantitative assessment of related substances in the compound ketoconazole and clobetasol propionate cream by HPLC-TOF-MS and HPLC. J Pharm Anal, 2019; 9:156-162. https://doi.org/10.1016/j.jpha.2018.08.006
Whan BK, Dana J, Jensen Y. Diagnosis and management of psoriasis. Can Fam Physician, 2017; 63:278-85.