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

<b>Aim &amp; objective: </b>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<b>/</b>MS) method for the simultaneous estimation of both drugs. <b>Materials &amp; methods: </b>A quality-by-design (QbD) approach was used for the optimization of the nanoemulsion, and US FDA guidelines were followed for method validation. <b>Results: </b>Multiple reaction monitoring transitions were used for L-ORM (459.05<b>→</b>98.50), RAL (475.00<b>→</b>112.02) and internal standard (180.10<b>→</b>110.2). Analytes were resolved in a C18 column with 80:20 v<b>/</b>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<b>/</b>ml. Pharmacokinetic results of free L-ORM–RAL and the L-ORM–RAL nanoemulsion showed Cmax of free L-ORM – 70.65 <b> </b><b>} </b>16.64, free RAL 13.53 <b> </b><b>} </b>2.72, LORM nanoemulsion 65.07 <b> </b><b>} </b>14.0 and RAL-nanoemulsion 59.27 <b> </b><b>} </b>17.44 ng<b>/</b>ml. <b>Conclusion: </b>Future findings will contribute to the treatment of postmenopausal osteoporosis and breast cancer using L-ORM and RAL.