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

• Published in: Journal of pharmaceutical and biomedical analysis 2014-11, Vol.100, p.50-57
• Main Authors: Taevernier, Lien, Veryser, Lieselotte, Vandercruyssen, Kirsten, D’Hondt, Matthias, Vansteelandt, Stijn, De Saeger, Sarah, De Spiegeleer, Bart
• Format: Article
• Language: English
• Subjects: Adsorption; Beauvericin; Bioanalytical UHPLC-MS/MS method; Calibration; Chromatography, High Pressure Liquid - methods; Chromatography, High Pressure Liquid - standards; Depsipeptides - chemistry; Depsipeptides - metabolism; Diffusion Chambers, Culture; Drug Stability; Enniatins; 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; Transdermal Franz diffusion cell
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2014.07.021

•We developed a high-throughput bioanalytical UHPLC-MS/MS method for BEA and ENNs.•Significant adsorption to glass occurs, depending on solvent composition.•BEA and ENNs are chemically stable under in vitro transdermal test conditions. 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%.