Stability-indicating validation of acitretin and isoacitretin in human plasma by LC-ESI-MS/MS bioanalytical method and its application to pharmacokinetic analysis

LC‐ ESI‐ MS/MS simultaneous bioanalytical method was developed to determine acitretin and its metabolite isoacitretin in human plasma using acitretin‐d3 used as the internal standard for both analytes. The compounds were extracted using protein precipitation coupled with liquid–liquid extraction wit...

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Bibliographic Details
Published in:	Biomedical chromatography Vol. 25; no. 6; pp. 680 - 688
Main Authors:	Kumar, Ajay, Monif, Tausif, Khuroo, Arshad, Sasmal, Dinakar, Goswami, Dipanjan, Lahkar, Vijay Kumar
Format:	Journal Article
Language:	English
Published:	Chichester, UK John Wiley & Sons, Ltd 01-06-2011
Subjects:	Acitretin - blood Acitretin - pharmacokinetics acitretin-isoacitretin: LC-ESI-MS/MS Area Under Curve Chromatography, Liquid - methods Drug Stability Humans Least-Squares Analysis Male method validation Photolysis Reproducibility of Results Sensitivity and Specificity Tandem Mass Spectrometry - methods
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Summary:	LC‐ ESI‐ MS/MS simultaneous bioanalytical method was developed to determine acitretin and its metabolite isoacitretin in human plasma using acitretin‐d3 used as the internal standard for both analytes. The compounds were extracted using protein precipitation coupled with liquid–liquid extraction with flash freezing technique. Negative mass transitions (m/z) of acitretin, isoacitretin and acitretin‐d3 were detected in multiple reactions monitoring (MRM) mode at 325.4 → 266.3, 325.2 → 266.1 and 328.3 → 266.3, respectively, with a turbo ion spray interface. The chromatographic separation was achieved on an Ascentis‐RP amide column (4.6 × 150 mm, 5 µm) with mobile phase delivered in isocratic mode. The method was validated over a concentration range of 1.025–753.217 ng/mL for acitretin and 0.394–289.234 ng/mL for isoacitretin with a limit of quantification of 1.025 and 0.394 ng/mL. The intra‐day and inter‐day precisions were below 8.1% for acitretin and below 13.8% for isoacitretin, while accuracy was within ±7.0 and ±10.6% respectively. For the first time, the best possible conditions for plasma stability of acitretin and isoacitretin are presented and discussed with application to clinical samples. Copyright © 2010 John Wiley & Sons, Ltd.
Bibliography:	istex:BACBD29890BFE1A0E13508044711BBBF955735E2 ark:/67375/WNG-56KWPPKB-S ArticleID:BMC1503 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0269-3879 1099-0801
DOI:	10.1002/bmc.1503