Publications by authors named "Chandrasekar Kuppan"

2 Publications

  • Page 1 of 1

Impurity profiling and stability-indicating method development and validation for the estimation of assay and degradation impurities of midostaurin in softgel capsules using HPLC and LC-MS.

Biomed Chromatogr 2021 Jul 31:e5222. Epub 2021 Jul 31.

Department of Science and Humanities, JMJ College for Women, Tenali, India.

Midostaurin (MDS) is used for the treatment of acute myeloid leukemia, myelodysplastic syndrome, and advanced systemic mastocytosis. MDS softgel capsule samples were subjected to stress testing per International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines for impurity profiling study. MDS underwent extensive degradation under stress testing (acid, alkaline, oxidative, photolytic, thermolytic, and hydrolysis conditions) and formed four degradation products (DPs). MDS and its DPs were separated well from one another with good resolution using reserved-phase HPLC using an Inertsil ODS-3V column (250 × 4.6 mm, 5 μm) and a mobile phase of ammonium formate (40 mM) and acetonitrile. The stability-indicating characteristic of the newly developed method was proven for the estimation of MDS assay, and its organic impurities were free from interference. The validated method exhibited excellent linearity, accuracy, precision, specificity, detection limit, and quantitation limit within 25 min run time. Stress testing, robustness, and solution stability were performed to ensure the continuous performance of the developed method. The peak fractions of DPs formed under stress testing were isolated and characterized using LC-MS, H and C NMR, IR, and UV-Vis. The structure of the major DPs was predicted as DP1 based on the spectral data. The proposed method is effectively used for MDS in bulk drug and finished formulations in the pharmaceutical industry.
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http://dx.doi.org/10.1002/bmc.5222DOI Listing
July 2021

[Impurity profile of macitentan in tablet dosage form using a stability-indicating high performance liquid chromatography method and forced degradation study].

Se Pu 2019 Jan;37(1):100-110

Department of Science and Humanities, VIGNAN's Foundation for Science, Technology & Research(VFSTR), Vadlamudi, Guntur(Dist.)522213, India.

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 tablets using a binary solvent-based gradient elution method using reversed phase-high performance liquid chromatography. 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 ≥ 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) HO, 80℃/15 min, thermolysis:at 105℃/16 h and photolysis:UV light at 200 Wh/m; 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 impurity determination, which is applicable to the pharmaceutical industry.
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http://dx.doi.org/10.3724/SP.J.1123.2018.06032DOI Listing
January 2019
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