title: Determination of arotinoid acid in human plasma by liquid chromatography-tandem mass spectrometry.
abstract: Arotinoid acid (Ro 13-7410) is the third generation of synthetic retinoid, which was developed for the treatment of psoriasis and other hyperkeratotic skin disorders. The therapeutically active dose is less than 0.5microg/kg body weight/day. To investigate the pharmacokinetics of arotinoid acid, a sensitive and selective liquid chromatographic-tandem mass spectrometric method (LC-MS/MS) for the determination of arotinoid acid in human plasma was developed and validated. The sample processing was carried out in the dark to minimize photodegradation of the analytes. Arotinoid acid and the internal standard (IS), acitretin, were extracted from plasma samples using solid phase extraction with Oasis HLB cartridges. Chromatographic separation was achieved on a Zorbax Extend C(18) column (150mmx4.6mm, i.d., 5microm) using methanol:acetonitrile:5mM ammonium acetate (48:32:20, v/v/v) as the mobile phase at a flow rate of 0.8mL/min. The detection was carried out in multiple reaction monitoring (MRM) mode via negative electrospray ionization (ESI) interface. The lower limit of quantification (LLOQ) achieved was 37.1pg/mL with intra-day and inter-day precision (RSD) of 8.7% and 8.5%, and accuracy (RE) of 2.0%. Inter-day and intra-day RSD for three quality control levels (QCs) across validation runs were less than 11.0% and the accuracy ranged from 1.9% to 3.3%. The validated LC-MS/MS method was applied to a phase I clinical pharmacokinetic study after a single oral administration of 40microg arotinoid trometamol to healthy subjects.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 646 Songtao Road, Shanghai 201203, PR China.
authors.forename: Pan
authors.initials: P
authors.lastname: Deng
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chen
authors.forename: Yunbiao
authors.initials: Y
authors.lastname: Tang
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Wang
authors.forename: Hongwen
authors.initials: H
authors.lastname: Zhang
authors.forename: Dafang
authors.initials: D
authors.lastname: Zhong
mesh_terms: D017255:Acitretin / Q000032:analysis; D001565:Benzoates / Q000097:blood* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D015203:Reproducibility of Results; D012176:Retinoids / Q000097:blood* / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D001565:Benzoates; D012176:Retinoids; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid; D017255:Acitretin