title: An LC-MS/MS method for the determination of digitoxigenin in skin samples and its application to skin permeation and metabolic stability studies.
abstract: An LC-MS/MS method was developed for the determination of digitoxigenin in mice skin samples. Chromatographic separation was achieved on an Agilent Poroshell 120 EC-C18 column. Mass spectrometric detection was achieved by a triple-quadrupole mass spectrometer equipped with an ESI interface operating in a positive ionization mode. Quantification was performed using selective reaction monitoring of the precursor-product ion transitions of m/z 375.5→339 for digitoxigenin and m/z 391.5→337 for internal standard (IS). The calibration curves were linear over the concentration range of 1.00-500ng/mL. The intra- and inter-batch precision was no more than 10.6% of the coefficient of variation and the accuracy was within ±8.1% of the actual values. This validated method has been successfully applied to skin permeation and skin metabolic stability studies of digitoxigenin in mice. The steady-state flux and lag time of digitoxigenin permeated across the full-thickness mice skin were 1.86±0.45μg/cm2/h and 0.46±0.18h, respectively. The metabolism of digitoxigenin in the skin was not detected in our study.
authors.affiliation: Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV, USA.
authors.forename: Xinchi
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Turley
authors.affiliation: Marshall Institute for Interdisciplinary Research, Marshall University, Huntington, WV, USA.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Marshall Institute for Interdisciplinary Research, Marshall University, Huntington, WV, USA.
authors.forename: Sandrine V
authors.initials: SV
authors.lastname: Pierre
authors.affiliation: Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV, USA.
authors.forename: Hasan
authors.initials: H
authors.lastname: Koc
authors.affiliation: Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV, USA.
authors.forename: M Omar
authors.initials: MO
authors.lastname: Khan
authors.affiliation: Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV, USA; Marshall Institute for Interdisciplinary Research, Marshall University, Huntington, WV, USA. Electronic address: haoj@marshall.edu.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Hao
mesh_terms: D000818:Animals; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004073:Digitoxigenin / Q000737:chemistry*; D004355:Drug Stability; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012867:Skin / Q000737:chemistry*; D013552:Swine; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004073:Digitoxigenin
keywords: Digitoxigenin; LC–MS/MS; Mice; Permeation; Skin metabolic stability; Skin tissue