title: 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.
abstract: 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(18) 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 m/z 808.5 → 527.5 (docetaxel) and m/z 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-β-cyclodextrin (HP-β-CD), and Taxotere, were administered to rats at a dose of 5 mg/kg. For SID530 and Taxotere, the mean C(0) values were 1494 and 1818 ng/mL, respectively, and the AUC(last) 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.
authors: College of Pharmacy, Seoul National University, Seoul, 151-742, Republic of Korea.
authors: Tae Kon
authors: TK
authors: Kim
authors: In Sook
authors: IS
authors: Kim
authors: Hye Hyun
authors: HH
authors: Yoo
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D019540:Area Under Curve; D002853:Chromatography, Liquid / Q000379:methods; D000077143:Docetaxel; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods; D043823:Taxoids / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D047392:beta-Cyclodextrins / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: C574494:SID530; D043823:Taxoids; D047392:beta-Cyclodextrins; D000077143:Docetaxel; D000073738:2-Hydroxypropyl-beta-cyclodextrin