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Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

Development and Validation of Novel UPLC-MS/MS Method for the Analysis of Macitentan in Pharmaceutical Formulations

Author(s): Mevlut Albayrak* and Alptug Atila

Volume 15, Issue 5, 2019

Page: [554 - 559] Pages: 6

DOI: 10.2174/1573412915666190314142531

Price: $65

Abstract

Introduction: Macitentan is an endothelin receptor antagonist drug used in the treatment of pulmonary arterial hypertension.

Materials and Methods: A new, sensitive, simple, accurate and rapid ultra-performance liquid chromatography in combination with tandem triple quadruple mass spectrometry (UPLC-MS/MS) method has been developed and validated for the determination of macitentan in pharmaceutical formulations. Macitentan and bosentan which are used as internal standard (IS) were detected using atmospheric pressure chemical ionization (APCI) in positive ion, multiple reaction monitoring (MRM) mode by monitoring mass transitions (precursor to product) m/z 589.1→203.3 and 552.6→311.5, respectively. Chromatographic separation was carried out on reverse phase C18 column (5 µm, 4.6 * 150 mm). Water containing 0.2 % acetic acid in acetonitrile (10:90, v/v) was used as the mobile phase in the isocratic elution. The system was optimized with injection volume of 10 µL, column temperature of 35 °C and flow rate of 1 mL min-1 Retention times were 1.97 min for macitentan and 1.72 min for IS.

Results and Discussion: The calibration curve with a high correlation coefficient (0.9997) was linear range 0.5-500 ng mL-1. The lower limit of quantitation (LLOQ) and average recovery values were determined as 0.5 ng mL-1 and 99.7 %, respectively. The developed novel method has been successfully applied for the determination of macitentan in pure form and pharmaceutical formulations.

Conclusion: The present method is the first study developed and validated for the determination of macitentan from the pharmaceutical preparations and pure form by UPLC-MS/MS method in the literature.

Keywords: Macitentan, pulmonary arterial hypertension, UPLC-MS/MS, validation, pharmaceutical formulations, specificity.

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[1]
Hoeper, M.M. Definition, classification, and epidemiology of pulmonary arterial hypertension. in Seminars in respiratory and critical care medicine. 2009. © Thieme Medical Publishers
[2]
Montani, D.; Gunther, S.; Dorfmuller, P.; Perros, F.; Girerd, B.; Garcia, G.; Jais, X.; Savale, L.; Artaud-Macari, E.; Price, L.C. Pulmonary arterial hypertension. Orphanet J. Rare Dis., 2013, 8(1), 97-125.
[3]
Bruderer, S.; Hopfgartner, G.; Seiberling, M.; Wank, J.; Sidharta, P.N.; Treiber, A.; Dingemanse, J. Absorption, distribution, metabolism, and excretion of macitentan, a dual endothelin receptor antagonist, in humans. Xenobiotica, 2012, 42(9), 901-910.
[4]
Steriade, A.; Seferian, A.; Jais, X.; Savale, L.; Jutant, E.; Parent, F.; Sitbon, O.; Humbert, M.; Simonneau, G.; Montani, D. The potential for macitentan, a new dual endothelin receptor antagonist, in the treatment of pulmonary arterial hypertension. Ther. Adv. Respir. Dis., 2014, 8(3), 84-92.
[5]
Pulido, T.; Adzerikho, I.; Channick, R.N.; Delcroix, M.; Galiè, N.; Ghofrani, H.; Jansa, P.; Jing, Z.; Le Brun, F.; Mehta, S. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N. Engl. J. Med., 2013, 369(9), 809-818.
[6]
Yu, L.; Zhou, Y.; He, X.; Li, H.; Chen, H.; Li, W. Simultaneous determination of macitentan and its active metabolite in human plasma by liquid chromatography-tandem mass spectrometry. J. Chromatogr. B , 2015, 1002, 358-363.
[7]
de Kanter, R.; Sidharta, P.; Delahaye, S.; Gnerre, C.; Segrestaa, J.; Buchmann, S.; Kohl, C.; Treiber, A. Physiologically-based pharmacokinetic modeling of macitentan: prediction of drug–drug interactions. Clin. Pharmacokinet., 2016, 55(3), 369-380.
[8]
Enderle, Y.; Witt, L.; Wilkens, H.; Grunig, E.; Haefeli, W.; Burhenne, J. Simultaneous quantification of endothelin receptor antagonists and phosphodiesterase 5 inhibitors currently used in pulmonary arterial hypertension. J. Pharm. Biomed. Anal., 2017, 143, 291-298.
[9]
Purushothaman, M.; Subramanian, R. Bioanalytical method validation for determination of macitentan in K2EDTA human plasma by LC-MS/MS. Int. J. Chemtech Res., 2017, 10(10), 752-761.
[10]
Patel, C.D.; Guttikar, S.; Patel, B.H. Development and validation of bioanalytical method for macitentan in human plasma using liquid chromatography-tandem mass spectrometry. Int. J. Pharm. Chem. Biol. Sci., 2018, 8(1), 43-52.
[11]
Issac, M.; Dingemanse, J.; Sidharta, P.N. Pharmacokinetics of macitentan in patients with pulmonary arterial hypertension and comparison with healthy subjects. J. Clin. Pharmacol., 2017, 57(8), 997-1004.
[12]
Ahn, L.; Kim, S.; Yi, S.; Dingemanse, J.; Lim, K.; Jang, I.; Yu, K. Pharmacokinetic–pharmacodynamic relationships of macitentan, a new endothelin receptor antagonist, after multiple dosing in healthy Korean subjects. Am. J. Cardiovasc. Drugs, 2014, 14(5), 377-385.
[13]
Kummer, O.; Haschke, M.; Hammann, F.; Bodmer, M.; Bruderer, S.; Regnault, Y.; Dingemanse, J.; Krahenbuhl, S. Comparison of the dissolution and pharmacokinetic profiles of two galenical formulations of the endothelin receptor antagonist macitentan. Eur. J. Pharm. Sci., 2009, 38(4), 384-388.
[14]
Sidharta, P.N.; van Giersbergen, P.L.M.; Dingemanse, J. Safety, tolerability, pharmacokinetics, and pharmacodynamics of macitentan, an endothelin receptor antagonist, in an ascending multiple‐dose study in healthy subjects. J. Clin. Pharmacol., 2013, 53(11), 1131-1138.
[15]
Landge, S.B. Development and validation of stability indicating rp-hplc method on core shell columnfor determination of degradation and process related impurities of macitentan-anti-hypertension drug. Int. J. Scientific Res. Sci. Technol., 2017, 3(10), 105-117.
[16]
Thummar, M.; Swain, D.; Gananadhamu, S. Separation and characterization of new forced degradation products of macitentan: A dual endothelin receptor antagonist. Chromatographia, 2018, 81(3), 525-531.
[17]
Manzoor, A.; Deepak, B.M.; Satishkumar, S.A.; Kuppast, I.J.; Anilkumar, S.M.; Ravi, M.C. RP-HPLC method development and validation for estimation of macitentan in tablet dosage form. WJPPS, 2014, 4(1), 881-887.
[18]
Unnisa, A.; Ali, S.S.; Kumar, S.S. Development and validation of rp-hplc-pda method for the estimation of macitentan in bulk and tablet dosage forms. Indo Am. J. Pharmaceut. Res., 2014, 4(9), 3836-3843.
[19]
Lakshmi, D. Quality by Design Based HPLC method development of macitentan and its related compounds in bulk drugs. JPDDR, 2016, 5(6), 1-5.
[20]
FDA, Food and Drug Administration, US Department of Health and Human Services, Guidance for industry, bioanalytical method validation. https://www.fda.gov/downloads/drugs/guidances/ucm070107.pdf2018.

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