Determination of fenticonazole enantiomers by LC-ESI-MS/MS and its application to pharmacokinetic studies in female rats
| Autor: | Zhenbin Feng, Xiao-Heng Tan, Wen-Jun Che, Qiaogen Zou, Zunjian Zhang |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Quality Control
Spectrometry Mass Electrospray Ionization Antifungal Agents Electrospray ionization Mass spectrometry Tandem mass spectrometry High-performance liquid chromatography Rats Sprague-Dawley Fenticonazole Drug Discovery medicine Protein precipitation Animals Chromatography High Pressure Liquid Chromatography Chemistry Imidazoles Reproducibility of Results Stereoisomerism Reference Standards Triple quadrupole mass spectrometer Rats Area Under Curve Female Indicators and Reagents Enantiomer medicine.drug |
| Zdroj: | Arzneimittel-Forschung. 61(10) |
| ISSN: | 0004-4172 |
| Popis: | A simple, rapid, and specific high-performance liquid chromatograph coupled with a tandem mass spectrometry method has been developed and validated for the determination of fenticonazole (CAS 72479-26-6) enantiomers in rat plasma. Simple protein precipitation by acetonitrile was utilized for extracting analytes from the plasma samples. Chromatography separation was performed on a C18 analytical column (150 mm x 2.0 mm, 5 microm) with a mobile phase consisting of methanol-10 mM aqueous ammonium acetate (adjusted to pH 3.5 with acetic acid) (90:10, v/v) at a flow rate of 0.2 ml/min. Detection was carried out on a triple quadrupole mass spectrometer equipped with electrospray ionization (ESI) source, and operated in multiple-reaction monitoring (MRM) mode. The calibration curves were linear over the range 0.5 -200 ng/ml (r > 0.99). The relative recoveries of R-(-)-fenticonazole and its enantiomer were better than 85%. The intra- and inter-day precisions (R.S.D.%) and deviations of the assay accuracies were less than 10%. This newly developed and validated method was successfully applied to pharmacokinetic studies after administration at a single dose of 20 mg/ kg R-(-)-fenticonazole nitrate and its enantiomer to female rats per vagina. The Cmax value of S-(+)-fenticonazole was greater than that of R-(-)-fenticonazole by 1.36-fold, whereas, the t(1/2) beta and MRT values of R-(-)-fenticonazole were longer than those of its enantiomer by 1.95- and 1.24-fold. The results indicated that S-(+)-fenticonazole was faster in absorption and elimination in female rat. But, the Tmax and AUC(0-12) values for each of fenticonazole enantiomers were not significantly different. |
| Databáze: | OpenAIRE |
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