RP-HPLC METHOD DEVELOPMENT AND VALIDATION OF MACITENTAN WITH ITS KNOWN AND UNKNOWN DEGRADATION IMPURITIES IN ITS TABLET DOSAGE FORM
Objective: To develop and validate macitentan with its known and unknown degradation impurities in its tablet dosage form.
Methods: The RP-HPLC method for macitentan and its impurities was developed and three potential degradation impurities MCA-02, MCA-01 and degradation impurity and N-propyl derivative and N-N dimethyl derivative process impurities were separated. Chromatographic separation was achieved within 70 min on Inertsil C8 (250*4.6 mm, 5 Âµm) column, Using mobile phase A [Ammonium acetate (ph 4.5 adjusted with glacial acetic acid)] and mobile phase B acetonitrile in gradient elution. Other hplc parameter which was optimized flow rate 1.5 ml/min, detection wavelength 266 nm, column oven temperature 30 Â° C and injection volume 20Î¼l. macitentan was subjected to forced degradation also known as stress testing. It was validated as per ICH guidelines.
Results: The drug showed extensive degradation in acidic and basic conditions, a slight degradation in oxidative condition. The developed method was statistically validated for linearity (0.45-2.25 ppm). The result of precision (%RSD<5), robustness, LOD(0.15 ppm) and LOQ(0.45 ppm) are well within limits.% Recovery at LOQ, 50%, 100% and 150% was found to be within limit 80-120 %.
Conclusion: RP-HPLC method was successfully developed with satisfactory separation of macitentan and its impurities. The proposed method was found to be specific, accurate, precise and robust can be used for estimation of macitentan and its impurities and can be successfully employed in the routine analysis of macitentan.
2. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med 2004;351:1425.
3. Satoskar RS, Bhandarkar SD, Ainapure SS. Pharmacology and pharmacotherapeutics. 16th ed. Mumbai: Popular prakashan; 2003. p. 401.
4. Chopra S, Badyal DK, Baby PC, Cherian D. Pulmonary arterial hypertension-advances in pathophysiology and management. Indian J Pharmacol 2012;44:4-11.
5. Patel MM, Patel CJ, Mishra S. Development and stability indicating chromatographic method for simultaneous of sacubitril and valsartan in pharmaceutical dosage form. Int J Appl Pharm 2017;9:1-8.
6. Ahmed M, Deepak BM, Shetty SA, Vijaya KC, Aradhya. Development andvalidation of first order derivative Spectrophotometric method for estimation ofmacitentan in bulk and tablet dosage form. Int J Universal Pharm BioSci 2015;4:269-75.
7. Ahmed M, Deepak BM, Shetty SA, Kuppast IJ, Anilkumar SM, MC Ravi. RP-HPLC method development and validation for estimation of macitentanintablet dosage form. J Pharm Pharm Sci 2014;4:881.
8. Lixiu Yu, Ying Zhou. Simultaneous determination of macitentan and its metabolite in human plasma by liquid chromatography tandem mass spectrometry J. Chromatography B 2015;1002:358.
9. D Lakshmi, P Hitesh Kumar, M Praveen, Reddy Praksh TVS, G Manish, J Jayachandran. Quality by design based HPLC method development of macitentan and its related compound in bulk drugs. J Pharma Drug Deilvery 2016;5:1.
10. Quality Assurance of Pharmaceuticals, A compendium of guidelines and related materials; WHO, Geneva; 1997. p. 119:24.
11. ICH Q3A and Q3B (R2). Impurities in New Drug Substances and Drug Products, 2006. International Conference on Harmonization (ICH) (2005) Harmonized Tripartite Guideline on, Topic Q2(R1), Validation of Analytical Procedures: Text and Methodology, Geneva; 2005;1:13.
12. ICH Q2 (R1) Validation of Analytical Procedure; 2005. p. 14.
13. Ahmed M, Deepak BM, Shetty SA, Kuppast IJ, Anilkumar SM, Ravi MC. RP-HPLC method development and validation for estimation of macitentan in tablet dosage form. J Pharm Pharma Sci 2015;4:887.