Development of stability-indicating LC method assisted by Design of Experiment for fenticonazole cream analysis in presence of degradation product

Fenticonazole is an antifungal drug widely used in a cream formulation including as a generic medicine. Stability studies of fenticonazole in a cream formulation are very scarce. In this research, we intent to contribute to generic medicines quality control and provide reliable data seeking for insertion of fenticonazole monograph in official compendia. Therefore, in this work it was studied the behavior of fenticonazole under several conditions and developed a stability-indicating LC method to separate the degradation products and quantify the drug in presence of them, using the Design of Experiments (DoE) as tool to achieve robust and easy transferable method. Fenticonazole stability was evaluated under aqueous, alkaline (0.1 M NaOH), acidic (0.1 M HCL) and oxidative (3% v/v, H2O2) at ambient temperature and heating at 90°C, over 6 hours. The drug shows to be unstable under all stressed test conditions. It was completely degraded under acid medium with arising of degradation products. The robust and stability indicating LC method was validated. It is able to reveal the fenticonazole instability and to separate its degradation product with accuracy and precision (CV ˂ 2%) and without any placebo interferences.(AU)

Determination of fenticonazole in human plasma by HPLC-MS/MS and its application to pharmacokinetic studies / 药物分析学报

Two simple and sensitive high performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) methods were developed and validated for the determination of fenticonazole in human plasma after percutaneous and intravaginal administration. Mifepristone was used as an internal standard (IS), and simple protein precipitation by acetonitrile containing 2%acetic acid was utilized for extracting the analytes from the plasma samples. Chromatographic separation was performed on a Kinetex XB-C18 column. The quantitation was performed by a mass spectrometer equipped with an electrospray ionization source in multiple reactions monitoring (MRM) positive ion mode using precursor-to-product ion transitions of m/z 455.2–199.1 for fenticonazole and m/z 430.2–372.3 for mifepristone. The validated linear ranges of fenticonazole were 5–1000 pg/mL and 0.1–20 ng/mL in plasma for the methods A and B, respectively. For the two methods, the accuracy data ranged from 85% to 115%, the intra- and inter-batch precision data were less than 15%, the recovery data were more than 90%, and no matrix interference was observed. The methods A and B were successfully validated and applied to the pharmacokinetic studies of fenticonazole gel in Chinese healthy volunteers after percutaneous and intravaginal administration, respectively.

Determination of Residual Organic Solvents in Fenticonazole Nitrate by Headspace Gas Chromatography / 中国药师

Objective:To establish a method for the determination of dichloromethane, methanol and ethanol in fenticonazole ni-trate. Methods:The samples were detected by headspace GC. The column was OV-1301(30 m × 0. 53 mm,3. 0 μm), the detector was FID with nitrogen as the carrier gas, the detector temperature was 250 ℃ and the injector temperature was 200 ℃. Results:The linear range of dichloromethane, methanol and ethanol was 2. 436-21. 924(r=0. 998 8), 12. 268-110. 412(r=0. 999 5) and 20. 052-180. 468 μg·ml-1(r=0. 996 9) with the average recovery of 99. 30% (RSD=2. 36%), 100. 21%(RSD=1. 07%) and 100. 15%(RSD=1. 21%)(n=9), respectively. Conclusion:The detection method is sensitive, accurate and reliable, and can be used in the quality control of fenticonazole nitrate.