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Arzneimittelforschung 2011; 61(10): 587-593
DOI: 10.1055/s-0031-1300557
Antibiotics · Antimycotics · Antiparasitics · Antiviral Drugs · Chemotherapeutics · Cytostatics
Editio Cantor Verlag Aulendorf (Germany)

Determination of fenticonazole enantiomers by LC-ESI-MS/MS and its application to pharmacokinetic studies in female rats

Zhenbin Feng
1   Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, P. R. China
2   Center for Instrumental Analysis, China Pharmaceutical University, Nanjing, P. R. China
,
Qiaogen Zou
3   Biology and Pharmacy Engineer Department, Nanjing University of Technology, Nanjing, P. R. China
,
Xiaoheng Tan
1   Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, P. R. China
2   Center for Instrumental Analysis, China Pharmaceutical University, Nanjing, P. R. China
,
Wenjun Che
3   Biology and Pharmacy Engineer Department, Nanjing University of Technology, Nanjing, P. R. China
,
Zunjian Zhang
1   Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, P. R. China
2   Center for Instrumental Analysis, China Pharmaceutical University, Nanjing, P. R. China
› Author Affiliations
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Publication History

Publication Date:
01 February 2012 (online)

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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 × 2.0 mm, 5 µm) 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 t1/2 ß 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.

Key words

Antifungal agent - Enantiomer - Fenticonazole - Pharmacokinetics - Liquid chromatography/tandem mass spectrometry (LC-MS/MS)
 

  • References

  • 1 Fromting RA. Overview of medically important antifungal azole derivatives. Clin Microbiol Rev. 1988; 1 (2) 187-217
    PubMedSearch in Google Scholar
  • 2 Veraldi S, Milani R. Topical fenticonazole in dermatology and gynaecology: current role in therapy. Drugs. 2008; 68 (15) 2183-94
    CrossrefPubMedSearch in Google Scholar
  • 3 Antonopoulou S, Aoun M, Alexopoulos EC, Baka S, Logothetis E, Kalambokas T et al. Fenticonazole activity measured by the methods of the European committee on antimicrobial susceptibility testing and CLSI against 260 Candida vulvovaginitis isolates from two European regions and annotations on the prevalent genotypes. Antimicrob Agents Chemother. 2009; 53 (5) 2181-4
    CrossrefPubMedSearch in Google Scholar
  • 4 Qian MR, Zeng S. Pharmacokinetics of chiral drugs. Asian J Drug Metab Pharmacokinet. 2003; 3: 99-103
    PubMedSearch in Google Scholar
  • 5 Hong YJ, Gao LB, Zeng S. Enantioselective analytical methods in chiral drug metabolism. J Chin Pharm Sci. 2008; 17: 177-82
    PubMedSearch in Google Scholar
  • 6 Rentsch KM. The importance of stereoselective determination of drugs in the clinical laboratory. J Biochem Biophys Methods. 2002; 54: 1-9
    CrossrefPubMedSearch in Google Scholar
  • 7 Quaglia MG, Donati E, Desideri N, Fanali S, Dauria FD, Tecca M. Chiral discrimination by HPLC and CE and antifungal activity of racemic fenticonazole and its enantiomers. Chirality. 2002; 14: 449-454
    CrossrefPubMedSearch in Google Scholar
  • 8 Speed W, Long JM, Simmonds RJ, Enos TA. The development and validation of a high performance liquid chroma-tography(HPLC)/tandem mass spectrometry assay for fenticonazole in human plasma and comparison with an HPLC-UV method. Rapid Commun Mass Spectrom. 1995; 9: 1452-6
    CrossrefPubMedSearch in Google Scholar
  • 9 FDA, Guidance for Industry, Bioanalytical Method Validation, May 2001.
    PubMed