Journal: Journal of Pharmacy Research

Article Id: JPRS-PA-0000115
Title: LC and LC/MS approach for quantification of everolimus and its degradants and application in stress analysis
Category: Pharmaceutical Analysis
Section: Research Article
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    Objective: Everolimus is the 40-O-(2-hydroxyethyl) derivative of sirolimus and a potent inhibitor of mammalian target of Rapamycin (mTOR). It is used as an immunosuppressant to prevent organ rejection, treatment of renal carcinoma and as restenotic inhibitor in drug eluting coronary stents. The objective of the present study is to develop an LC and LC/MS method for quantification and structural elucidation of everolimus and its degradants in various stress conditions and strategize the stability issues in various applications. Method: Everolimus was subjected to different ICH prescribed stress conditions of thermal stress, hydrolysis and photolysis. Quantification and further structural elucidation was done by a rapid and systematic strategy based liquid chromatography–mass spectrometry (LC–MS) and liquid chromatography–tandem mass spectrometry (LC–MS–MS) sub structural technique. An acceptable separation of degradants was achieved using a C -18 column with mobile phase comprising of 70:30 acetonitrile: water with 0.1% glacial acetic acid, pH 5.4 held isocratic for 10 min.. The PDA detection wavelength was from 200nm to 800nm. The scanning range of mass was set at 100 to 1030Daltons with capillary and cone voltages at 4.0 kV and 70.0V respectively. The source temperature was set at 1000C and desolvation temperature at 3500C. ESI micro mass quadrapole detector and data management software - Mass Lynx ver. 4.1 were used. Result: Subjecting everolimus to different stress conditions resulted in degradants of different molecular weights. Molecular weights of the degradants are found to be 634, 559, 507, 437,309 Daltons (Da) in basic condition 707, 633, 549, 431, 298 Da in acidic condition and 633, 559, 429, 780, 707 Da under accelerated conditions of temperature. Conclusion: The results indicate that everolimus is highly sensitive to acid, base, light and temperature. The present method developed helped in proposing structures of degradants and further provide base for future work involving the analysis of everolimus.

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    Author(s) Name:

    Spandana K, Srinivas P, Prashanth S, Anil Kumar A, Madhu B, Divya P, Vidya Sagar J*

    Affiliation(s) Name:

    Bio Analytical, Research and Development Division, Relisys Medical Devices Ltd (RMDL), Hyderabad-501 510, Andhra Pradesh,India.

     

    *Corresponding author.
    Dr. J. Vidya Sagar
    Chief Scientist
    Bio Analytical, Research and Development Division,
    Relisys Medical Devices Ltd (RMDL),
    Hyderabad-501 510,
    Andhra Pradesh. India.

    Email: sagar@relisysmedicaldevices.org


    Received on:21-11-2013; Revised on: 08-12-2013; Accepted on:11-12-2013

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    Author:

    Spandana K, Srinivas P, Prashanth S, Anil Kumar A, Madhu B, Divya P, Vidya Sagar J*

    Title:LC and LC/MS approach for quantification of everolimus and its degradants and application in stress analysis
    Journal:Journal of Pharmacy Research
    Vol(issue):8 (February)
    Year:2014
    Page No: (152-161)
  • Experimental Methods Keywords

    Methodology:LC and LC/MS
    Research Materials:everolimus and its degradants

Keywords

Degradants Everolimus Immunosuppressant Stress analysis.

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