UHPLC-MS/MS method for the determination of the cyclic depsipeptide mycotoxins beauvericin and enniatins in in vitro transdermal experiments

J Pharm Biomed Anal. 2014 Nov:100:50-57. doi: 10.1016/j.jpba.2014.07.021. Epub 2014 Jul 29.

Abstract

Currently, dermal exposure data of cyclic depsipeptide mycotoxins beauvericin and enniatins are completely absent with a lack of local skin and systemic kinetics, despite their widespread skin contact and intrinsic hazard. Therefore a sensitive and specific bioanalytical high-throughput UHPLC-MS/MS method was developed for the quantitative and simultaneous determination of cyclic depsipeptide mycotoxins beauvericin and enniatins (A, A1, B, B1, D, E, C/F) in human skin Franz diffusion cell samples. The limits of detection ranged between 10 and 17pg/ml, while the total run time was only 4.5min. There was no significant effect of endogenous skin compounds on the mycotoxin MS signal observed, and the accuracy (0.68-24.68% bias) and precision (0.57-10.70% RSD) were considered acceptable for our purposes. Moreover, it was demonstrated that these cyclic depsipeptides are stable for at least 7 days when formulated in different organic or aqueous mixtures. Finally, adsorption to glass did occur: at least 50% ethanol or acetonitrile is required to prevent significant adsorption effects, which could be as high as 45%.

Keywords: Adsorption; Beauvericin; Bioanalytical UHPLC-MS/MS method; Cyclic depsipeptide mycotoxins; Enniatins; Transdermal Franz diffusion cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Calibration
  • Chromatography, High Pressure Liquid / methods*
  • Chromatography, High Pressure Liquid / standards
  • Depsipeptides / chemistry
  • Depsipeptides / metabolism*
  • Diffusion Chambers, Culture
  • Drug Stability
  • Glass / chemistry
  • High-Throughput Screening Assays / methods*
  • High-Throughput Screening Assays / standards
  • Humans
  • Kinetics
  • Limit of Detection
  • Linear Models
  • Permeability
  • Reference Standards
  • Skin / metabolism*
  • Skin Absorption*
  • Spectrometry, Mass, Electrospray Ionization* / standards
  • Tandem Mass Spectrometry* / standards

Substances

  • Depsipeptides
  • enniatins
  • beauvericin