Evaluation of Deuterium-Labeled Internal Standard for the Measurement of Venetoclax by HPLC-ESI -Tandem Mass Spectrometry

    Published on:September 2018
    Journal of Young Pharmacists, 2018; 10(4):392-398
    Original Article | doi:10.5530/jyp.2018.10.87
    Authors:

    Srikanth Inturi*1,2, Ratna Kumari Yejerla2, Naga Suresh kumar Jujjuru2, Prameela Rani Avula1

    1Department of Pharmaceutical Sciences, University College of Pharmaceutical Sciences, Acharya Nagarjuna University, Guntur, Andhra Pradesh, INDIA.

    2Department of Pharmaceutical Sciences, Narasaraopeta Institute of Pharmaceutical Sciences, Narasaraopet, Guntur, Andhra Pradesh, INDIA.

    Abstract:

    Objective: Venetoclax is a selective, potent, first-in-class BCL-2 inhibitor that restores apoptosis in cancer cells and has demonstrated clinical efficacy in a variety of haematological malignancies. There is no reported evidence for its measurement in human plasma. Method: A simple, sensitive and specific high-throughput HPLC-ESI-Tandem Mass Spectrometric method was developed for the estimation of Venetoclax (VX) in human plasma using Venetoclax-D8 (VXD8) as an internal standard (IS). Chromatographic separation was performed on Zorbax SB-C18, 75 x 4.6 mm, 3.5 mm, 80 Å column with an isocratic mobile phase composed of Methanol and 5mM Ammonium acetate in the ratio of (70:30 v/v), at a flow-rate of 0.6 mL/min. The proton adducts of VX and VXD8 were detected at m/z 868.12 ®321.54 and 876.9®329.7 respectively, using multiple reaction monitoring (MRM) positive mode respectively. The Liquid-Liquid extraction method was used to extract the analyte and IS. Results: The method was successfully validated over linearity concentration range of 10.0-10000.0 pg/mL with the correlation coefficient (r2) ≥ 0.9997. This method demonstrated intra and inter-day precision within 5.7 to 7.7 and 5.95 to 8.5 and % Accuracy within 96.3 to 98.7 and 98 to 100.4 %. Venetoclax was found to be stable throughout freeze-thawing cycles, bench top, postoperative stability studies. Conclusion: The method was suitable and conveniently applicable to pharmacokinetic and bioavailability studies for estimation of Venetoclax in biological matrices by HPLC-MS/MS.

    Key words: Deuterium, Pharmacokinetic, Plasma, Proton adduct, Venetoclax.

     

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