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Quantitative determination of paclitaxel and its metabolites, 6α‐hydroxypaclitaxel and p‐3′‐hydroxypaclitaxel,in human plasma using column‐switching liquid chromatography/tandem mass spectrometry
Authors:Hiroaki Yamaguchi  Asuka Fujikawa  Hajime Ito  Nobuaki Tanaka  Ayako Furugen  Kazuaki Miyamori  Natsuko Takahashi  Jiro Ogura  Masaki Kobayashi  Takehiro Yamada  Nariyasu Mano  Ken Iseki
Affiliation:1. Faculty of Pharmaceutical Sciences, Hokkaido University, , Sapporo, 060‐0812 Japan;2. Graduate School of Medicine, Hokkaido University, , Sapporo, 060‐8638 Japan;3. Department of Pharmacy, Hokkaido University Hospital, , Sapporo, 060‐8648 Japan;4. Department of Pharmaceutical Sciences, Tohoku University Hospital, , Sendai, 980‐8574 Japan
Abstract:A column‐switching liquid chromatography/electrospray ionization tandem mass spectrometry to determine paclitaxel and its metabolites, 6α‐hydroxypaclitaxel and p‐3′‐hydroxypaclitaxel, in human plasma was developed. The analytical system had a Shim‐Pack MAYI‐ODS (10 × 4.6 mm i.d.) trapping column with deproteinization ability that concentrates analytes and removes water‐soluble components. This method covered a linearity range of 5–5000 ng/mL of concentrations in plasma for paclitaxel, a range of 0.87–870 ng/mL for 6α‐hydroxypaclitaxel and a range of 0.87–435 ng/mL for p‐3′‐hydroxypaclitaxel. The intra‐day precision and inter‐day precision of analysis were less than 11.1%, and the accuracy was within ±14.4% at concentrations of 5, 50, 500 and 5000 ng/mL for paclitaxel, 0.87, 8.7, 87 and 870 ng/mL for 6α‐hydroxypaclitaxel, and 0.87, 8.7, 87 and 435 ng/mL for p‐3′‐hydroxypaclitaxel. The total run time was 30 min. Our method was successfully applied to clinical pharmacokinetic investigation. Copyright © 2012 John Wiley & Sons, Ltd.
Keywords:paclitaxel  metabolite  human plasma  column‐switching
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