色谱2019，Vol.37Issue(1)：100-110,11.DOI:10.3724/SP.J.1123.2018.06032
Impurity profile of macitentan in tablet dosage form using a stability-indicating high performance liquid chromatography method and forced degradation study
Narasimha S LAKKA 1Chandrasekar KUPPAN 2Parthasarathy RANGASAMY1
作者信息
- 1. Department of Science and Humanities,VIGNAN's Foundation for Science,Technology &Research (VFSTR),Vadlamudi,Guntur (Dist.)522213,India
- 2. Department of Analytical Research &Development,Sinotherapeutics Inc.,Shanghai 201210,China
- 折叠
摘要
Abstract
Macitentan (MAC)is a pulmonary arterial hypertension (PAH)drug marketed as a tablet and often has stability issues in the final dosage form. Quantitative determination of MAC and its associated impurities in tablet dosage form has not been previously reported. This study quantified impurities present in Macitentan tab-lets using a binary solvent-based gradient elution method using reversed phase-high performance liquid chroma-tography. The developed method was validated per International Conference on Harmonization (ICH)guidelines and the drug product was subjected to forced degradation studies to evaluate stability. The developed method efficiently separated the drug and impurities (48 min)without interference from solvents,excipients,or other impurities. The developed method met all guidelines in all characteristics with recoveries ranging from 85％-115％,linearity with r2≥0. 9966,and substantial robustness. The stability-indicating nature of the method was evaluated using stressed conditions (hydrolysis:1 N HCl at 80 ℃/15 min;1 N NaOH at 25 ℃/45 min;humidity stress (90％ relative humidity)at 25 ℃ for 24 h,oxidation:at 6％(v/v)H2 O2 ,80 ℃/15 min,thermolysis:at 105 ℃/16 h and photolysis:UV light at 200 Wh/m2;Fluorescent light at 1. 2 million luxh). Forced degradation experiments showed that the developed method was effective for impurity profiling. All stressed samples were assayed and mass balance was>96％. Forced degradation results indicated that MAC tablets were sensitive to hydrolysis (acid and alkali)and thermal conditions. The developed method is suitable for both assay and impu-rity determination,which is applicable to the pharmaceutical industry.关键词
reverse phase-high performance liquid chromatography (RP-HPLC)/stability-indicating method/forced degradation study/binary solvent gradient/endothelin receptor antagonist (ERA)/pulmonary arterial hypertension (PAH)/macitentan (MAC)/impurity profilingKey words
reverse phase-high performance liquid chromatography (RP-HPLC)/stability-indicating method/forced degradation study/binary solvent gradient/endothelin receptor antagonist (ERA)/pulmonary arterial hypertension (PAH)/macitentan (MAC)/impurity profiling分类
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Narasimha S LAKKA,Chandrasekar KUPPAN,Parthasarathy RANGASAMY..[J].色谱,2019,37(1):100-110,11.
