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Research Article

Enhanced oral bioavailability of levormeloxifene and raloxifene by nanoemulsion: simultaneous bioanalysis using liquid chromatography-tandem mass spectrometry

    Divya Chauhan

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India

    Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, India

    ,
    Debalina Maity

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India

    ,
    Pavan K Yadav

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India

    Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, India

    ,
    Sachin Vishwakarma

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India

    ,
    Arun Agarwal

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India

    ,
    Manish K Chourasia

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India

    Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, India

    &
    Jiaur R Gayen

    *Author for correspondence:

    E-mail Address: jr.gayen@cdri.res.in

    Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India

    Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, India

    Published Online:https://doi.org/10.2217/nnm-2024-0023

    Aim & objective: Levormeloxifene (L-ORM) and raloxifene (RAL) are selective estrogen receptor modulators used in the treatment of postmenopausal osteoporosis and breast cancer. Here, we developed and validated a liquid chromatography-tandem mass spectrometry (LC–MS/MS) method for the simultaneous estimation of both drugs. Materials & methods: A quality-by-design (QbD) approach was used for the optimization of the nanoemulsion, and US FDA guidelines were followed for method validation. Results: Multiple reaction monitoring transitions were used for L-ORM (459.05→98.50), RAL (475.00→112.02) and internal standard (180.10→110.2). Analytes were resolved in a C18 column with 80:20 v/v% acetonitrile (ACN), 0.1% formic acid in triple-distilled water as a mobile phase. The developed method was linear over a concentration range of 1–600 ng/ml. Pharmacokinetic results of free L-ORM–RAL and the L-ORM–RAL nanoemulsion showed Cmax of free L-ORM – 70.65 ± 16.64, free RAL 13.53 ± 2.72, L-ORM nanoemulsion 65.07 ± 14.0 and RAL-nanoemulsion 59.27 ± 17.44 ng/ml. Conclusion: Future findings will contribute to the treatment of postmenopausal osteoporosis and breast cancer using L-ORM and RAL.

    Graphical abstract

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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