Preparation and in vitro/in vivo evaluation of anastrozole reservoir-type intravaginal ring

This report details the preparation of anastrozole (ATZ) reservoir-type intravaginal ring (IVR) and the detection of the concentration of ATZ in beagle dog plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS). An ATZ reservoir-type IVR which included ATZ silicone elastomer core and a nonactive silicone layer was manufactured by reaction injection moulding at 80°C for 20 min. An in vitro release experiment was performed under sink conditions and the samples were determined by high-performance liquid chromatography. A bioanalytical method was developed and validated for determination of ATZ in beagle dog plasma for IVR development. The analytical method consisted of the extraction of plasma samples and determination of ATZ by LC-MS/MS using buspirone as the internal standard. Separation was achieved on a Kinetex-C₁₈ 110A column (3 × 30 mm, 2.6 μm, Phenomenex) using step-gradient mobile phase and an isocratic flow rate consisting of formic acid. Protonated ions formed by a turboion spray in the positive mode was used to detect the analyte (ATZ) and internal standard. The MS-MS detection was performed on a triple quadrupole mass spectrometer equipped with electrospray ionization source. The mass spectrometer was operated in the multiple reaction monitoring mode. The mass transition ion-pair was followed as m/z from 294.10 to 225.08 for anastrozole and m/z from 386.23 to 122.11 for buspirone. The results proved that the correlation between in vitro and in vivo analyses was relatively good.