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Determination of arotinoid acid in human plasma by liquid chromatography-tandem mass spectrometry.
J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Oct 01; 877(27):2983-8.JC

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.

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Authors+Show Affiliations

Deng P
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 646 Songtao Road, Shanghai 201203, PR China.
Chen X
No affiliation info available
Tang Y
No affiliation info available
Wang Y
No affiliation info available
Zhang H
No affiliation info available
Zhong D
No affiliation info available

MeSH

AcitretinBenzoatesChromatography, LiquidDrug StabilityHumansLeast-Squares AnalysisMaleReproducibility of ResultsRetinoidsSensitivity and SpecificitySolid Phase ExtractionTandem Mass Spectrometry

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19632163

Citation

Deng, Pan, et al. "Determination of Arotinoid Acid in Human Plasma By Liquid Chromatography-tandem Mass Spectrometry." Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, vol. 877, no. 27, 2009, pp. 2983-8.
Deng P, Chen X, Tang Y, et al. Determination of arotinoid acid in human plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2009;877(27):2983-8.
Deng, P., Chen, X., Tang, Y., Wang, Y., Zhang, H., & Zhong, D. (2009). Determination of arotinoid acid in human plasma by liquid chromatography-tandem mass spectrometry. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 877(27), 2983-8. https://doi.org/10.1016/j.jchromb.2009.07.017
Deng P, et al. Determination of Arotinoid Acid in Human Plasma By Liquid Chromatography-tandem Mass Spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Oct 1;877(27):2983-8. PubMed PMID: 19632163.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Determination of arotinoid acid in human plasma by liquid chromatography-tandem mass spectrometry. AU - Deng,Pan, AU - Chen,Xiaoyan, AU - Tang,Yunbiao, AU - Wang,Yongqing, AU - Zhang,Hongwen, AU - Zhong,Dafang, Y1 - 2009/07/17/ PY - 2009/03/09/received PY - 2009/05/25/revised PY - 2009/07/10/accepted PY - 2009/7/28/entrez PY - 2009/7/28/pubmed PY - 2009/12/30/medline SP - 2983 EP - 8 JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JO - J Chromatogr B Analyt Technol Biomed Life Sci VL - 877 IS - 27 N2 - 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. SN - 1873-376X UR - https://www.unboundmedicine.com/medline/citation/19632163/Determination_of_arotinoid_acid_in_human_plasma_by_liquid_chromatography_tandem_mass_spectrometry_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1570-0232(09)00533-9 DB - PRIME DP - Unbound Medicine ER -