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Evaluation of calcipotriol transdermal permeation through pig, rat and mouse skin using liquid chromatography–tandem mass spectrometry
Author(s) -
Li Xiaojiao,
Wang Jing,
Li Guoqing,
Lin Changqing,
Zhang Xueju,
Sun Yantong,
Yang Yan,
Gu Jingkai
Publication year - 2013
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.2984
Subject(s) - calcipotriol , chemistry , chromatography , permeation , liquid chromatography–mass spectrometry , mass spectrometry , high performance liquid chromatography , electrospray ionization , transdermal , extraction (chemistry) , tandem mass spectrometry , elution , electrospray , membrane , psoriasis , pharmacology , dermatology , biochemistry , medicine
ABSTACT 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‐C 18 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. Copyright © 2013 John Wiley & Sons, Ltd.