Separation of Four Impurities and Degradants by LC: A Case of Bicalutamide

Year 2021, Volume: 41 Issue: 2, 82 - 92, 01.06.2021

Ashu Mittal Alankar Shrivastava

https://doi.org/10.52794/hujpharm.895556

Abstract

Bicalutamide is an antiandrogen preparation primarily indicated for the treatment of treat prostate carcinoma. Although several analytical methods have been described, a liquid chromatography method determination in the presence of impurities (Impurity A, B, C and BIC-2) and degradation products is still unexamined. Thus, a simple chromatography method is illustrated for bicalutamide in the presence of impurities and degradation products under stress conditions. The separation method is reverse phase, with octyl column on Agilent HPLC 1100 series equipment. The mobile phase was combination of phosphate buffer and acetonitrile. The developed method was validated according to International Conference on Harmonisation Guidelines. Bicalutamide and its four process related impurities and degradants were successfully separated by using proposed method. The method was found to be linear between 70 to 130 µg/ml, the regression equation y = 19.647x + 18.645
with correlation coefficient value of 0.9999. The method was found to be accurate and precise enough to be used for analysis. The LOD and LOQ values found were 0.031, 0.031, 0.031, 0.028, 0.029 µg/ml and 0.083, 0.083, 0.103, 0.075, 0.098 µg/ml for impurity A, B, C, BIC-2 and BCL respectively. The proposed analytical methodology is simple, robust, specific and accurate enough for routine analysis of bicalutamide API and its other four process related impurities and degradants.

Keywords

: Analytical methods, Bicalutamide, bicalutamide impurities, method development, analysis

Supporting Institution

NA

Project Number

NA

Separation of Four Impurities and Degradants by LC: A Case of Bicalutamide

Abstract

Bicalutamide is an antiandrogen preparation primarily indicated for the treatment of treat prostate carcinoma. Although several analytical methods have been described, a liquid chromatography method determination in the presence of impurities (Impurity A, B, C and BIC-2) and degradation products is still unexamined. Thus, a simple chromatography method is illustrated for bicalutamide in the presence of impurities and degradation products under stress conditions. The separation method is reverse phase, with octyl column on Agilent HPLC 1100 series equipment. The mobile phase was combination of phosphate buffer and acetonitrile. The developed method was validated according to International Conference on Harmonisation Guidelines. Bicalutamide and its four process related impurities and degradants were successfully separated by using proposed method. The method was found to be linear between 70 to 130 µg/ml, the regression equation y = 19.647x + 18.645 with correlation coefficient value of 0.9999. The method was found to be accurate and precise enough to be used for analysis. The LOD and LOQ values found were 0.031, 0.031, 0.031, 0.028, 0.029 µg/ml and 0.083, 0.083, 0.103, 0.075, 0.098 µg/ml for impurity A, B, C, BIC-2 and BCL respectively. The proposed analytical methodology is simple, robust, specific and accurate enough for routine analysis of bicalutamide API and its other four process related impurities and degradants.

Keywords

Analytical methods, Bicalutamide, bicalutamide impurities, method development, analysis

Project Number

NA

References

• 1. Sadeghi-Gandomani HR, Yousefi MS, Rahimi S, Yousefi SM, Karimi-Rozveh A, Hosseini S, Mahabadi AA, Abarqui HF, Borujeni NN, Salehiniya H. The incidence, risk factors, and knowledge about the prostate cancer through worldwide and Iran. World J Cancer Res. 2017; 4 (4): e972.
• 2. Hassanipour-Azgomi S, Mohammadian-Hafshejani A, Ghoncheh M, Towhidi F, Jamehshorani S, Salehiniya H. Incidence and mortality of prostate cancer and their relationship with the Human Development Index worldwide. Prostate Int. 2016 Sep;4(3):118-24. DOI: 10.1016/j.prnil.2016.07.001.
• 3. Shen HC, Balk SP. Development of androgen receptor antagonists with promising activity in castration-resistant prostate cancer. Cancer Cell. 2009 Jun 2;15(6):461-3. DOI: 10.1016/j.ccr.2009.05.005.
• 4. PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 2375, Bicalutamide; [cited 2020 Oct. 30]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Bicalutamide.
• 5. Eric S. Bicalutamide. xPharm: The Comprehensive Pharmacology Reference 2007, pp. 1-5. DOI: https://doi.org/10.1016/B978-008055232-3.62975-7
• 6. Folake AO, Amy EM, McEwan IJ. Androgen Receptor Ligands: Agonists and Antagonists. Reference Module in Biomedical Sciences. Encyclopedia of Reproduction (Second Edition). vol 1; 2018: 234-241.
• 7. Parihar JS, Kim IY. Second-Line Hormonal for Castrate-Resistant Prostate Cancer. Prostate Cancer (Second Edition). Science and Clinical Practice. 2016; 533-540.
• 8. Reddy VP. Organofluorine Compounds as Anticancer Agents. Organofluorine Compounds in Biology and Medicine. 2015; 265-300. DOI: https://doi.org/10.1016/B978-0-444-53748-5.00009-5.
• 9. Piotrowski Z, Greenberg RE. Antiandrogen Monotherapy in the Treatment of Prostate Cancer. Prostate Cancer (Second Edition). Science and Clinical Practice. 2016, 515-521. DOI: https://doi.org/10.1016/B978-0-12-800077-9.00055-4.
• 10. Sancheti PP, Vyas VM, Shah M, Karekar P, Pore YV. Spectrophotometric estimation of Bicalutamide in tablets. Indian J Pharm Sci. 2008; 70(6): 810–812. DOI: 10.4103/0250-474X.49131.
• 11. Balaram VM, Rao JV, Khan MMA, Sharma JVC, Sreedevi K. Visible spectrophotometric determination of Bicalutamide in bulk drug and pharmaceutical formulations. Int J Chem Sci.: 7(3), 2009, 1606-1612.
• 12. Smith A, Manavalan R, Kannan K, Rajendiran N. Spectrofluorimetric Determination of Bicalutamide in Formulation and Biological Fluids. Asian J Chem. 21(1);2009: 459-466.
• 13. Ventura E, Gadaj A, Monteith G, Ripoche A, Healy J, Botrè F, Sterk S, Buckley T, Mooney MH. Development and validation of a semi-quantitative ultra-high performance liquid chromatography-tandem mass spectrometry method for screening of selective androgen receptor modulators in urine. J Chromatogr A, 2019;1600:183–196. DOI: https://doi.org/10.1016/j.chroma.2019.04.050.
• 14. Suresh PS, Kumar SV, Kumar A, Mullangi R. Development of an LC-MS/MS method for determination of bicalutamide on dried blood spots: application to pharmacokinetic study in mice. Biomed. Chromatogr. 2015; 29: 254–260. DOI 10.1002/bmc.3268.
• 15. Sadutto D, Ferretti R, Zanitti L, Casulli A, Cirilli R. Analytical and semipreparative high performance liquid chromatography enantio separation of bicalutamide and its chiral impurities on an immobilized polysaccharide-based chiral stationary phase. J Chromatogr A, 2016. DOI: http://dx.doi.org/doi:10.1016/j.chroma.2016.04.011
• 16. Ramarao NT, Vidyadhara S, Sasidhar RLC, Deepti B, Surendra Yadav R. Development and Validation of LC-MS/MS Method for the Quantification of Chiral Separated R-Bicalutamide in Human Plasma. Ame J Analy Chem, 2013; 4: 63-76. DOI: http://dx.doi.org/10.4236/ajac.2013.42009.
• 17. Ventura E, Gadaj A, Buckley T, Mooney MH. Development of a multi-residue high-throughput UHPLC-MS/MS method for routine monitoring of SARM compounds in equine and bovine blood. Drug Test Anal. 2020;12:1373–1379. DOI: 10.1002/dta.2875.
• 18. Gadaj A, Ventura E, Ripoche A, Mooney MH. Monitoring of selective androgen receptor modulators in bovine muscle tissue by ultra-high performance liquid chromatography-tandem mass spectrometry. Food Chem X. 2019 ;4:100056. DOI: 10.1016/j.fochx.2019.100056.
• 19. Gomes FP, Garcia PL. Development and validation of a simple and sensitive high performance liquid chromatographic method for the simultaneous determination of anastrozole, bicalutamide, tamoxifen, and their synthetic impurities. Talanta. 2012;101:495-503. DOI: 10.1016/j.talanta.2012.10.004.
• 20. Kim B, Hwa J, Seunghwan S, Lee LS, Yoon SH. Liquid Chromatography Tandem Mass Spectrometry Determination of Bicalutamide in Human Plasma and Application to a Bioequivalence Study. J Bioanal Biomed 3: 098-102. DOI:10.4172/1948-593X.1000051.
• 21. Rao RN, Raju AN, Nagaraju D. An improved and validated LC method for resolution of bicalutamide enantiomers using amylose tris-(3,5-dimethylphenylcarbamate) as a chiral stationary phase. J Pharma Biomed Analy 2006;42: 347–353.
• 22. Rao R N, Narasa RA, Narsimha R. Isolation and characterization of process related impurities and degradation products of bicalutamide and development of RP-HPLC method for impurity profile study. J Pharm Biomed Anal. 2008;46(3):505-19.
• 23. Raman Nanduri VVSS, Prasad Adapa VSS, Kura RR. Development and Validation of Stability-Indicating HPLC and UPLC Methods for the Determination of Bicalutamide, J Chromatogr Sci, 2012;50(4): 316–323, DOI: https://doi.org/10.1093/chromsci/bms010.
• 24. Pandit UJ, Khan I, Wankar S, Raj KK, Limaye SN. Development of an electrochemical method for the determination of bicalutamide at the SWCNT/CPE in pharmaceutical preparations and human biological fluids. Anal Methods, 2015;7:10192-10198. DOI: https://doi.org/10.1039/C5AY02025E.
• 25. Saravanan G, Rao BM, Ravikumar M, Suryanarayana MV, Someswararao N, Acharyulu PVR. A Stability-Indicating LC Assay Method for Bicalutamide. Chroma 2007;66: 219–222. DOI: https://doi.org/10.1365/s10337-007-0280-0.
• 26. Sharma K, Pawar GV, Giri S, Rajagopal S, Mullangi R. Development and validation of a highly sensitive LC-MS/MS-ESI method for the determination of bicalutamide in mouse plasma: application to a pharmacokinetic study. Biomed Chromatogr, 2012;26(12): 1589-95. DOI: https://doi.org/10.1002/bmc.2736.
• 27. Singh AK, Chaurasiya A, Jain GK, Awasthi A, Asati D, Mishra G, Khar RK, Mukherjee R. High performance liquid chromatography method for the pharmacokinetic study of bicalutamide SMEDDS and suspension formulations after oral administration to rats. Talanta. 2009 Jun 15;78(4-5):1310-4. DOI: 10.1016/j.talanta.2009.01.058.
• 28. Subramanian GS, Karthik A, Baliga A, Musmade P, Kini S. High-performance thin-layer chromatographic analysis of bicalutamide in bulk drug and liposomes. J Planar Chromatography. Modern TLC. 2009;22(4):273-276. DOI: https://doi.org/10.1556/JPC.22.2009.4.6.
• 29. Raghu K, Chandrasekar A, Sankaran KR. Electrochemical behavior and differential pulse voltametric determination of an antineoplastic drug bicalutamide and pharmaceuticals formulations using glassy carbon electrode. Inter J Chem Res, 2010;2:5-16. DOI: http://dx.doi.org/10.9735/0975-3699.2.2.5-16.
• 30. Hua-Bin L, Xiang-Rong X, Feng C. Determination of Iodine in Seawater: Methods and Applications. Comprehensive Handbook of Iodine Nutritional, Biochemical, Pathological and Therapeutic Aspects. 2009, Pages 2-13.
• 31. M. Sargent (Ed.), Guide to achieving reliable quantitative LC-MS measurements, RSC Analytical Methods Committee, 2013. ISBN 978-0-948926-27-3.
• 32. Boers J, Venema CM, de Vries EFJ, Hospers GAP, Boersma HH, Rikhof B, Dorbritz C, Glaudemans AWJM, Schröder CP. Serial [18F]-FDHT-PET to predict bicalutamide efficacy in patients with androgen receptor positive metastatic breast cancer. Eur J Cancer. 2021 Feb;144:151-161. doi: 10.1016/j.ejca.2020.11.008.
• 33. Kandil SB, McGuigan C, Westwell AD. Synthesis and Biological Evaluation of Bicalutamide Analogues for the Potential Treatment of Prostate Cancer. Molecules. 2020 Dec 24;26(1):56. doi: 10.3390/molecules26010056.
• 34. Boers J, Venema CM, de Vries EFJ, Hospers GAP, Boersma HH, Rikhof B, Dorbritz C, Glaudemans AWJM, Schröder CP. Serial [18F]-FDHT-PET to predict bicalutamide efficacy in patients with androgen receptor positive metastatic breast cancer. Eur J Cancer. 2021 Feb;144:151-161. doi: 10.1016/j.ejca.2020.11.008.
• 35. Malinowski B, Wiciński M, Musiała N, Osowska I, Szostak M. Previous, Current, and Future Pharmacotherapy and Diagnosis of Prostate Cancer-A Comprehensive Review. Diagnostics (Basel). 2019 Oct 25;9(4):161. doi: 10.3390/diagnostics9040161.