title: A UHPLC-UV Method to Quantify Skin Deposition and Transdermal Permeation of Tizanidine Hydrochloride.
abstract: Tizanidine hydrochloride is an α2-adrenergic agonist used for the symptomatic relief of spasticity associated with multiple sclerosis or with spinal cord injury or disease. The objective of this study was to develop an isocratic, robust and sensitive ultra-high performance liquid chromatography method using UV detection for use in a project to develop a transdermal therapeutic system to deliver tizanidine across the skin. Isocratic separation was achieved using a C18 column and a mobile phase comprising a 80:20 mixture of 0.004% trifluoroacetic acid in water and MeCN (pH* 3.2) at a flow rate of 0.2 mL min(-1) Tizanidine eluted at 1.499 min and the total run time was 2 min. The method was specific, robust and the response was accurate, precise and linear from 17.4 to 290 ng mL(-1) In contrast to existing methods, the method developed here was validated over a concentration range so as to include the low concentrations frequently observed in transdermal permeation studies and in samples extracted from the cutaneous matrix. Its suitability for use in transdermal permeation studies was subsequently tested and confirmed in preliminary experiments using porcine skin in vitro.
authors.affiliation: Departamento de Farmacia, Facultad de Ciencias de la Salud, Instituto de Ciencias Biomédicas, Universidad CEU Cardenal Herrera, C/Del Pozo S/N 46115, Valencia, Spain School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, 30 Quai Ernest Ansermet 1211, Geneva, Switzerland.
authors.forename: Sergio
authors.initials: S
authors.lastname: del Río-Sancho
authors.affiliation: Centro de Reconocimiento Molecular y Desarrollo Tecnológico, Centro Mixto Universidad Politécnica de Valencia, Universidad de Valencia, Valencia, Spain Departamento de Farmacia y Tecnología Farmacéutica, Universidad de Valencia, Valencia, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Merino
authors.affiliation: Departamento de Farmacia, Facultad de Ciencias de la Salud, Instituto de Ciencias Biomédicas, Universidad CEU Cardenal Herrera, C/Del Pozo S/N 46115, Valencia, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: López-Castellano
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, 30 Quai Ernest Ansermet 1211, Geneva, Switzerland yogi.kalia@unige.ch.
authors.forename: Yogeshvar N
authors.initials: YN
authors.lastname: Kalia
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003000:Clonidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D057230:Limit of Detection; D010539:Permeability; D015203:Reproducibility of Results; D012867:Skin / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
chemical_list: C023754:tizanidine; D003000:Clonidine