title: Determination of fenticonazole enantiomers by LC-ESI-MS/MS and its application to pharmacokinetic studies in female rats.
abstract: 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.
authors.affiliation: Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, PR China.
authors.forename: Zhenbin
authors.initials: Z
authors.lastname: Feng
authors.forename: Qiaogen
authors.initials: Q
authors.lastname: Zou
authors.forename: Xiaoheng
authors.initials: X
authors.lastname: Tan
authors.forename: Wenjun
authors.initials: W
authors.lastname: Che
authors.forename: Zunjian
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007093:Imidazoles / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics*; D007202:Indicators and Reagents; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism
chemical_list: D000935:Antifungal Agents; D007093:Imidazoles; D007202:Indicators and Reagents; C033486:fenticonazole