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LC–MS–MS Study of the Pharmacokinetics of a 9-β-Dihydro-9,10-O-acetal Derivative of Docetaxel in Rats and Beagle Dogs

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An Erratum to this article was published on 03 June 2008

Abstract

SHR110008 is a representative 9-β-dihydro-9,10-O-acetal taxane with greater anticancer activity and less toxicity than docetaxel. To support a preclinical study of its pharmacokinetics and to predict the effect of 9-β-dihydro-9,10-O-acetal modification on its pharmacokinetic properties, we have developed a sensitive and rapid liquid chromatographic–tandem mass spectrometric method for quantitative analysis of SHR110008 in rat and dog plasma. Plasma was extracted with ethyl acetate. The analytes were separated on a 150 × 4.6 mm i.d., 5 μm particle, reversed-phase C18 column with 90:10 (v/v) methanol–0.1% formic acid as mobile phase at a flow rate of 0.3 mL min−1. Detection was performed by triple-quadrupole tandem mass spectrometry in selected reaction monitoring (SRM) mode with an electrospray ionization source. The precursor-to-product ion transition m/z 933 → 142 was used. The method was validated for accuracy and precision, and linearity in the two matrices was good. Lower limits of quantification (LLOQ) in rat and dog plasma were 5 and 2 ng mL−1, respectively. There were no stability-related problems in the procedure for analysis of SHR110008. The method was successfully used in a preclinical study of the pharmacokinetics of SHR110008 in rats and beagle dogs. The pharmacokinetics of SHR110008 were non-linear in rats and dogs. The elimination half-life ranged from 5.18 to 7.32 h for the rats and from 6.42 to 8.42 h for the dogs.

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Acknowledgments

We gratefully thank Professor Sun Fenzhi and Dr. Hao Haiping for kind assistance in the revision of the paper. This research was supported by the National High Technology Foundation of China (‘863’ Project, No. 2003AA2Z347A, 2005AA2Z3C70).

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Authors and Affiliations

  1. Key Laboratory of  Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24 Tong Jia Xiang Street, Box 210, Nanjing, Jiangsu, 210009, People’s Republic of China

    Xiaoling Hu, Jianguo Sun, Guangji Wang, Xiaoyan Zhu & Gang Hao

  2. Auckland Cancer Society Research Centre, Faculty of  Medical and Health Sciences, The University of Auckland, Auckland, New Zealand

    Yongchuan Gu & Frederik B. Pruijn

Authors
  1. Xiaoling Hu
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  2. Jianguo Sun
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  3. Guangji Wang
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  4. Xiaoyan Zhu
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  5. Gang Hao
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  6. Yongchuan Gu
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  7. Frederik B. Pruijn
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Correspondence to Xiaoling Hu.

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An erratum to this article can be found at http://dx.doi.org/10.1365/s10337-008-0680-9

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Hu, X., Sun, J., Wang, G. et al. LC–MS–MS Study of the Pharmacokinetics of a 9-β-Dihydro-9,10-O-acetal Derivative of Docetaxel in Rats and Beagle Dogs. Chroma 67, 883–892 (2008). https://doi.org/10.1365/s10337-008-0638-y

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  • DOI: https://doi.org/10.1365/s10337-008-0638-y

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