LC—MS/MS Studies for the Identification and Characterization of Degradation Products of Fenofibrate and Their Degradation Pathways

• Autorzy: Mulgund S. V. , Anbazhegan S. , Gabhe S. Y.
• Języki publikacji: EN

Abstrakty

EN

In the present study, the degradation behavior of Fenofibrate under different International Conference on Harmonization (ICH) suggested conditions was studied. Characterization of degradation products by liquid chromatography–tandem mass spectrometry (LC–MS/MS) studies in solution form was done, and the possible mechanism for the formation of degradants is discussed. Fenofibrate was subjected to different hydrolytic stress conditions and thermal stress condition (in solid form). Successful separation of drug from degradants was achieved on a C18 column using water–acetonitrile (25:75 v/v) as the mobile phase. Other high-performance liquid chromatography (HPLC) parameters were: flow rate, 1 mL min−1; detection wavelength, 286 nm; column temperature, 25 °C; and injection volume, 20 μL. The method was validated for linearity, precision, accuracy, robustness, and specificity and was stability-indicating one, based on the specificity studies. The drug degraded under acidic, basic, and oxidative hydrolytic stress while it was relatively stable towards neutral hydrolysis and thermal stress. The stressed samples were subjected to LC–MS/MS analysis. On the basis of spectral data, the structures of four degradation products and one interaction product were suggested. Degradation products were characterized to be isopropyl acetate, 2-[4-(4-chlorobenzoyl)phenoxy]-2-methyl propanoic acid, 4-hydroxy benzoic acid, and benzoic acid. The structure of one interaction product was proposed as methyl 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoate.

Słowa kluczowe

EN

Fenofibrate; stress studies; RP-HPLC; degradation; LC–MS/MS; characterization

• Wydawca: University of Silesia in Katowice ; Akademiai Kiado
• Czasopismo: Acta Chromatographica
• Rocznik: 2016
• Tom: Vol. 28, no. 2
• Strony: 159--173
• Opis fizyczny: Bibliogr. 37 poz., rys., tab.

Twórcy

autor

Mulgund S. V.

• Department of Quality Assurance Techniques, Sinhgad College of Pharmacy, Pune, Maharashtra, 411041, India and Jawaharlal Nehru Technological University, Hyderabad, India

autor

Anbazhegan S.

• Surya School of Pharmacy, Surya Nagar, GST Road, Vikravandi, Villupuram, Tamil Nadu, 605652, India

autor

Gabhe S. Y.

• Center for Advanced Research in Pharmaceutical Sciences, Poona College of Pharmacy, Bharati Vidyapeeth University, Pune, Maharashtra, 411038, India

Bibliografia

• [1] ICH, Q1A(R2), Stability Testing of New Drug Substances and Products, International Conference on Harmonization, IFPMA, Geneva, February, 2003
• [2] ICH, Q3A(R2), Impurities in New Drug Substances, International Conference on Harmonization, Draft, IFPMA, Geneva, October, 2006
• [3] ICH, Q3B(R2), Impurities in New Drug Products, International Conference on Harmonization, Draft, IFPMA, Geneva, June, 2006
• [4] A.K. Basak et. al., Adv. Drug Del. Rev., 59, 64–72 (2007)
• [5] D.K. Jain, P. Patel, S. Rajawat, and H.S. Chandel, Int. J. Pure Appl. Chem., 7(2), 139–2012 (2012)
• [6] European Pharmacopoeia, The Director for the Quality of Medicine of the Council of Europe, Strasbourg cedex, France, 2004, pp. 1581–1583
• [7] British Pharmacopoeia, The Medicine and Healthcare Products Regulatory Agency, British Pharma Commission Office, London, 2007, pp. 854–855
• [8] F.M.M. Salamaa, M.W.I. Nassarl, M.M.K. Sharaf, and A.M. Attia, Am. J. Anal. Chem., 2(3), 332–2011 (2011)
• [9] S.D. Kumara, M. Gupta, and R.P. Rao, Int. J. Biol. Pharm. Res., 1(2), 131–2010 (2010)
• [10] P.N. Dhabale and D.S. Gharge, Int. J. ChemTech Res., 2(1), 325–328 (2010)
• [11] R.R. Sevda, A.S. Ravetkar, and P.J. Shirote, Int. J. ChemTech Res., 3(2), 629–2011 (2011)
• [12] S. Sharma and P. Bhandari, J. Pharm. Res., 5, 2311–2314 (2012)
• [13] A. Karunakaran, V. Subhash, R. Chinthala, and J. Muthuvijayan, Stamford J. Pharm. Sci., 4, 58–63 (2011)
• [14] D. Nagavalli, S. Vijayashanthi, S. Jagan, and R. Lakshmisundram, Int. Res. J. Pharm., 2, 146–149 (2011)
• [15] B.G. Choudhari, J. Pharm. Sci. Innovation, 1, 44–48 (2012)
• [16] P.C. Bhamare, S.B. Bari, S. Natarajan, A.A. Patil, S.H. Patil, and P.T. Shirole, Asian J. Biochem. Pharm. Res., 2, 115–128 (2011)
• [17] S.V. Kutty, S.C. Eapen, M. Shameer, and P.P. Faizal, Int. J. Pharm. Sci. Drug Res., 4, 74–76 (2012).
• [18] S.V. Kutty, S.C. Eapen, A. Baby, and V.G. Prashanth, Int. J. Pharm. Res. Biosci., 1(1), (2012).
• [19] D. Nagavalli, B. Srinivas, and K. Chakravarthi, J. Pharm. Biomed. Sci., 4, 1–6. (2010)
• [20] G.V. Suresh Kumar and Y. Rajendraprasad, Int. J. PharmTech Res., 2, 2016–2021 (2010)
• [21] P.C. Bhamare, S.B. Bari, S. Natarajan, A.A. Patil, S.H. Patil, and P.T. Shirole, Int. J. PharmTech Res., 3, 505–515 (2011)
• [22] D.K. Jain, S. Rajawat, N. Jain, and H.S. Chandel, Search Res., 2, 131–133 (2011)
• [23] S.D. Bhinge, S.M. Malipatil, A. Jondhale, R. Hirave, and A.S. Savali, E-J. Chem., 9, 1223–1229 (2012)
• [24] A. Karunakaran, V. Subhash, R. Chinthala, and J. Muthuvijayan, Stamford J. Pharm. Sci., 4, 58–63 (2011)
• [25] A. Ajmeraa, B.S. Deshpande, P. Patela, K. Patela, S. Solankia, and K. Rathod, Int. J. Pharm. Pharm. Sci., 4, 206–209 (2012)
• [26] G.S. Devika, M. Sudhakar, and J.V. Rao, Int. J. Pharm. Pharm. Sci., 3, 311–315 (2011)
• [27] E. Kublin, E. Malanowicz, B. Kaczmarska-graczyk, and A.P. Mazurek, Acta Pol. Pharm. - Drug Res., 69, 139–143 (2012)
• [28] T. Deepan and P.K. Ambedkar, Eur. J. Appl. Sci., 3, 35–39 (2011)
• [29] El-A. Gindy, S. Emara, M.K. Mesbah, and G.M. Hadad, II Farmaco, 60, 425–438 (2005)
• [30] N. Jain, R. Raghuwanshi R, and D. Jain, Ind. J. Pharm. Sci., 70, 263–265 (2008)
• [31] N. Jain, R. Jain, S. Jain, and D.K. Jain, J. Pharm. Res., 2, 16–20 (2011)
• [32] M. Sudheer, M. Siva Prakash, G. Rajashekar, K.V. Hima Vani, P. Ramalingam, and Y. Reddy Padmanabha, J. Pharm. Res., 4, 3033–3039 (2011)
• [33] A.A. Kadav and D.N. Vora, J. Pharm. Biomed. Anal., 48, 120–126 (2008)
• [34] Z.A. Elsherif, S.S. Abas, M.H. Abdelwahab, and S.El. Weshahy, Int. J. Pharm. Pharm. Sci., 5, 886–896 (2013)
• [35] J. Santiago, A. Agüera, M. del Mar Gómez-Ramos, A.R. Fernández Alba, E.G. Calvo, R. Rosal, J. Hazard. Mater., 194, 30–41 (2011)
• [36] P.M. Lacroix, B.A. Dawson, R.W. Sears, D.B. Black, T.D. Cyr, and J.C. Ethier, J. Pharm. Biomed. Anal., 18, 383–402 (1998)
• [37] ICH, Q2 (R1), Validation of Analytical Procedures: Text and Methodology, International Conference on Harmonization, Geneva, November, 2005

Uwagi

PL

Opracowanie ze środków MNiSW w ramach umowy 812/P-DUN/2016 na działalność upowszechniającą naukę.