Simultaneous determination of docetaxel and ketoconazole in rat plasma by liquid chromatography/electrospray ionization tandem mass spectrometry
A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed and validated for simultaneous quantification of docetaxel and ketoconazole in rat plasma with paclitaxel as internal standard (IS). The analytes were extracted from rat plasma by using a liquid...
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Published in | Rapid communications in mass spectrometry Vol. 21; no. 6; pp. 1009 - 1018 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Chichester, UK
John Wiley & Sons, Ltd
01.01.2007
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Subjects | |
Online Access | Get full text |
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Summary: | A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed and validated for simultaneous quantification of docetaxel and ketoconazole in rat plasma with paclitaxel as internal standard (IS). The analytes were extracted from rat plasma by using a liquid‐liquid extraction technique with ethyl acetate and the LC separation was performed on a Cosmosil‐C18 analytical column (150 mm × 2.0 mm i.d., Nacalai Tesque Inc., Japan). The extracted samples were analyzed with LC/MS/MS, operating in selected reaction monitoring (SRM) mode. The SRM transitions of precursor ions to product ions were 830.3→549.1 (m/z) for docetaxel, 531.2→489.3 (m/z) for ketoconazole, and 876.7→307.9 (m/z) for the IS. The calibration curves were linear over the range of 2–500 ng/mL for docetaxel and 50–20 000 ng/mL for ketoconazole, with coefficients of correlation above 0.999. The limits of quantification for docetaxel and ketoconazole were both 2 ng/mL. The limit of detection for each analyte was 1 ng/mL. The intra‐ and inter‐day precision (CV) of analysis were within 7%, and the accuracy ranged from 95 to 110%. The overall recoveries for docetaxel and ketoconazole were about 89.0% and 91.1%, respectively. The total analysis time was only 9.0 min. This quantitation method was successfully applied to the simultaneous determination of docetaxel and ketoconazole in rat plasma and some potential interaction was found in the current coadministration pharmacokinetic study. This established method was also utilized in the in vitro and in vivo drug‐drug interaction study of docetaxel and ketoconazole (to be published). Copyright © 2007 John Wiley & Sons, Ltd. |
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Bibliography: | ArticleID:RCM2903 ark:/67375/WNG-SLM1FMSD-0 Key Lab of Drug Metabolism and Pharmacokinetics of Jiangsu Province - No. BM2001201 National '863' Project - No. 2003AA2Z347A; No. 2005AA2Z3C70 istex:F56DF0EA1B789512C095B9F0AB83DD27AA0FF356 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0951-4198 1097-0231 |
DOI: | 10.1002/rcm.2903 |