title: Evaluation of calcipotriol transdermal permeation through pig, rat and mouse skin using liquid chromatography-tandem mass spectrometry.
abstract: A rapid and sensitive liquid chromatography-tandem mass spectrometric method to evaluate the permeation and retention of calcipotriol in excised samples of pig, rat and mouse skin after application of a calcipotriol ointment has been developed and validated. After sample preparation of ointment, skin homogenate and receptor medium by liquid-liquid extraction, chromatography was performed on an Extend-C18 column using isocratic elution. Detection was by electrospray ionization in the negative ion mode using multiple-reaction monitoring of the precursor to product ion transitions of calcipotriol at m/z 411.1 → 393.5, and of lovastatin (internal standard) at m/z 403.2 → 101.2. The assay was linear in all matrices with LLOQs of 1, 0.5 and 40 ng/mL for skin homogenate, receptor medium and ointment samples respectively. In terms of the permeation profiles, it was found that calcipotriol permeated through all skins to only a limited extent over 20 h after application but was efficiently retained in all skins at a level at 20 h of between 40% (pig) and 60% (rat and mouse) of the applied dose. This indicates that calcipotriol ointment has the potential to provide sustained therapeutic benefit in the treatment of psoriasis with minimal systemic side effects.
authors.affiliation: Clinical Pharmacology Center, Research Institute of Translational Medicine, The First Bethune Hospital of Jilin University, Dongminzhu Street, Changchun, 130061, People's Republic of China; College of Life Science, Jilin University, Qianjin Street, Changchun, 130012, People's Republic of China; Phase I Clinical Trial Unit, The First Hospital of Jilin University, China-Frontage USA, Yunhe Street, Changchun, 130061, People's Republic of China.
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Guoqing
authors.initials: G
authors.lastname: Li
authors.forename: Changqing
authors.initials: C
authors.lastname: Lin
authors.forename: Xueju
authors.initials: X
authors.lastname: Zhang
authors.forename: Yantong
authors.initials: Y
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Jingkai
authors.initials: J
authors.lastname: Gu
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D012867:Skin / Q000737:chemistry / Q000378:metabolism*; D012869:Skin Absorption; D013552:Swine; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C055085:calcipotriene; D002117:Calcitriol
keywords: LC-MS/MS; calcipotriol; in vitro; psoriasis; skin permeation