Determination of docetaxel in rat plasma and its application in the comparative pharmacokinetics of Taxotere and SID530, a novel docetaxel formulation with hydroxypropyl‐β‐cyclodextrin. (27th July 2012)

• Record Type: Journal Article
• Authors: Kim, Tae Kon; Kim, In Sook; Yoo, Hye Hyun
• Is Part Of: Biomedical chromatography. Volume 27:Number 3(2013:Mar.)
• Page Start: 306
• Page End: 310
• Publication Date: 2012-07-27
• Subjects: Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.2792
• Languages: English
• ISSNs: 0269-3879

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>In this study, a sensitive, simple and reliable method for the quantification of docetaxel in rat plasma was developed and validated using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). The plasma samples were prepared by protein precipitation, and paclitaxel was used as an internal standard (IS). Chromatographic separation was achieved using a Gemini C<sub>18</sub> column (2.0 × 150 mm, 5 µm) with a mobile phase consisting of 0.1% formic acid–acetonitrile (30:70, v/v). The precursor–product ion pairs used for multiple reaction monitoring were <italic>m/z</italic> 808.5 → 527.5 (docetaxel) and <italic>m/z</italic> 854.2 → 286.5 (IS, paclitaxel). A calibration curve for docetaxel was constructed over the range 1–1000 ng/mL. The developed method was specific, precise and accurate, and no matrix effect was observed. The validated method was applied in a comparative pharmacokinetic study in which two docetaxel formulations, SID530, a new parenteral formulation of docetaxel with hydroxypropyl‐<italic>β</italic>‐cyclodextrin (HP‐<italic>β</italic>‐CD), and Taxotere, were administered to rats at a dose of 5 mg/kg. For SID530 and Taxotere, the mean <italic>C</italic><sub>0</sub> values were 1494 and 1818 ng/mL, respectively, and the AUC<sub>last</sub> values were 837 and 755 h ng/mL, respectively. These two formulations did not show any statistical differences with regard to the pharmacokinetic parameters, thus establishing that the SID530 and Taxotere products are pharmacokinetically comparable in male rats. Copyright © 2012 John Wiley & Sons, Ltd.</p> </abstract>