Development and validation of a LC-MS assay for the quantification of ikh12 a novel anti-tumor candidate in rat plasma and tissues and its application in a pharmacokinetic study

IKH12 is a novel histone deacetylase 6 selective inhibitor. A rapid and sensitive liquid chromatography tandem mass spectrometry method was developed and validated for the quantification of IKH12 in rat plasma and tissue with kendine 91 as internal standard (IS). The samples were prepared by liquid–...

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Bibliographic Details
Published in:	Biomedical chromatography Vol. 29; no. 8; pp. 1249 - 1258
Main Authors:	Otaegui, Dorleta, Masdeu, Carme, Aldaba, Eneko, Vara, Yosu, Zubia, Aizpea, San Sebastian, Eider, Alcalá, Maria, Villafruela, Sergio, Cossío, Fernando P., Rodriguez-Gascón, Alicia
Format:	Journal Article
Language:	English
Published:	England Blackwell Publishing Ltd 01-08-2015
Subjects:	analytical validation Animals Antineoplastic Agents - blood Chromatography, High Pressure Liquid - methods histone deacetylase inhibitor Histone Deacetylase Inhibitors - blood Hydroxamic Acids - blood IKH12 Limit of Detection liquid chromatography Liquid-Liquid Extraction - methods Male mass spectrometry Methyl Ethers - chemistry pharmacokinetics Proline - analogs & derivatives Proline - blood Rats, Wistar selective inhibitor Spectrometry, Mass, Electrospray Ionization - methods Tandem Mass Spectrometry - methods IKH12 analytical validation histone deacetylase inhibitor pharmacokinetics selective inhibitor liquid chromatography mass spectrometry
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Summary:	IKH12 is a novel histone deacetylase 6 selective inhibitor. A rapid and sensitive liquid chromatography tandem mass spectrometry method was developed and validated for the quantification of IKH12 in rat plasma and tissue with kendine 91 as internal standard (IS). The samples were prepared by liquid–liquid extraction with tert‐butyl methyl ether. The chromatographic separation was accomplished by using a Zorbax Extend C18 4.6 × 150 mm, 5 µm column, with a mobile phase consisting of methanol and 0.1% formic acid (75:25 v/v). Multiple reaction monitoring, using electrospray ionization in positive ion mode, was employed to quantitatively detect IKH12 and IS. The monitored transitions were set at m/z 418 → 252 and 444 → 169 for IKH12 and kendine 91, respectively. The calibration curve was linear over the concentration range 2–1000 ng mL−1. The intra‐ and inter‐assay precision and accuracy of the quality controls and the limit of quantification were satisfactory in all cases (according to European Medicines Agency guidelines). Stability studies showed that plasma samples were stable in the chromatography rack for 24 h and at −80 °C for 2 months and also after three freeze–thaw cycles. This method was successfully applied to a pharmacokinetic study of IKH12 in rat. Copyright © 2015 John Wiley & Sons, Ltd.
Bibliography:	istex:EC98DBCB15DD1901469BB3DF28971F1B57E22E7D ark:/67375/WNG-XQJLV9CJ-T ArticleID:BMC3414 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0269-3879 1099-0801
DOI:	10.1002/bmc.3414