Tags

Type your tag names separated by a space and hit enter

Quantitative determination of talatisamine and its pharmacokinetics and bioavailability in mouse plasma by UPLC-MS/MS.

Abstract

Talatisamine, as the efficacy ingredient of Aconitum, was known as a novel specific blocker for the delayed rectifier K+ channels in rat hippocampal neurons. In this study, a rapid, selective and reproducible UPLC-MS/MS separation method was established and fully validated for the quantitative determination of talatisamine levels in ICR (Institute of Cancer Research) mouse blood. A total of 24 healthy male ICR mice were divided into four groups that was administered talatisamine via intravenous at a dose of 1 mg/kg and oral administration of three doses (2, 4, 8 mg/kg). All blood samples were protein precipitate by using acetonitrile with an internal standard (IS) deltaline. The effective chromatographic separation was carried out through an UPLC BEH C18 analytical column (2.1 mm × 50 mm, 1.7 μm) with an initial mobile phase that consisted of acetonitrile and 10 mmol/L ammonium acetate aqueous solution (containing 0.1% formic acid) with a gradient elution pumped at a flow rate of 0.4 mL/min. Also, an electrospray ionization (ESI) was applied to quantify the talatisamine in the positive ions mode. The method validation demonstrated good linearity over the range of 1-1000 ng/mL (r2 ≥ 0.9993) for talatisamine in mouse blood with a lower limit of quantification (LLOQ) at 1 ng/mL. The accuracy values of the method were within 89.4% to 113.3%, and the matrix effects were between 103.2% and 106.3%. The mean extraction recoveries for talatisamine obtained from four concentrations of QC blood samples were exceeded 71.7%, and the relative standard deviation (RSD) both of intra- and inter-day precision values for replicate quality control samples did not exceed 15% respectively for all analytes during the assay validation. This method was successfully applied to the evaluation of the pharmacokinetic of talatisamine, regardless of intragastric or intravenous administration in mice. Based on the pharmacokinetics data, the bioavailability of talatisamine in mice was >65.0% after oral administration, exhibiting an excellent oral absorption.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China.

    ,

    The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China.

    ,

    Analytical and Testing Centre, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. Electronic address: lankywang@163.com.

    The Laboratory of Clinical Pharmacy, The People's Hospital of Lishui, Lishui 323000, China. Electronic address: zyf2808@126.com.

    Source

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31207562

    Citation

    Chen, Mengchun, et al. "Quantitative Determination of Talatisamine and Its Pharmacokinetics and Bioavailability in Mouse Plasma By UPLC-MS/MS." Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, vol. 1124, 2019, pp. 180-187.
    Chen M, Chen Y, Wang X, et al. Quantitative determination of talatisamine and its pharmacokinetics and bioavailability in mouse plasma by UPLC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2019;1124:180-187.
    Chen, M., Chen, Y., Wang, X., & Zhou, Y. (2019). Quantitative determination of talatisamine and its pharmacokinetics and bioavailability in mouse plasma by UPLC-MS/MS. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 1124, pp. 180-187. doi:10.1016/j.jchromb.2019.06.015.
    Chen M, et al. Quantitative Determination of Talatisamine and Its Pharmacokinetics and Bioavailability in Mouse Plasma By UPLC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Aug 15;1124:180-187. PubMed PMID: 31207562.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Quantitative determination of talatisamine and its pharmacokinetics and bioavailability in mouse plasma by UPLC-MS/MS. AU - Chen,Mengchun, AU - Chen,Yijie, AU - Wang,Xianqin, AU - Zhou,Yunfang, Y1 - 2019/06/08/ PY - 2019/03/01/received PY - 2019/05/17/revised PY - 2019/06/07/accepted PY - 2019/6/18/pubmed PY - 2019/6/18/medline PY - 2019/6/18/entrez KW - Bioavailability KW - Mice KW - Pharmacokinetics KW - Talatisamine KW - UPLC-MS/MS SP - 180 EP - 187 JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JO - J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. VL - 1124 N2 - Talatisamine, as the efficacy ingredient of Aconitum, was known as a novel specific blocker for the delayed rectifier K+ channels in rat hippocampal neurons. In this study, a rapid, selective and reproducible UPLC-MS/MS separation method was established and fully validated for the quantitative determination of talatisamine levels in ICR (Institute of Cancer Research) mouse blood. A total of 24 healthy male ICR mice were divided into four groups that was administered talatisamine via intravenous at a dose of 1 mg/kg and oral administration of three doses (2, 4, 8 mg/kg). All blood samples were protein precipitate by using acetonitrile with an internal standard (IS) deltaline. The effective chromatographic separation was carried out through an UPLC BEH C18 analytical column (2.1 mm × 50 mm, 1.7 μm) with an initial mobile phase that consisted of acetonitrile and 10 mmol/L ammonium acetate aqueous solution (containing 0.1% formic acid) with a gradient elution pumped at a flow rate of 0.4 mL/min. Also, an electrospray ionization (ESI) was applied to quantify the talatisamine in the positive ions mode. The method validation demonstrated good linearity over the range of 1-1000 ng/mL (r2 ≥ 0.9993) for talatisamine in mouse blood with a lower limit of quantification (LLOQ) at 1 ng/mL. The accuracy values of the method were within 89.4% to 113.3%, and the matrix effects were between 103.2% and 106.3%. The mean extraction recoveries for talatisamine obtained from four concentrations of QC blood samples were exceeded 71.7%, and the relative standard deviation (RSD) both of intra- and inter-day precision values for replicate quality control samples did not exceed 15% respectively for all analytes during the assay validation. This method was successfully applied to the evaluation of the pharmacokinetic of talatisamine, regardless of intragastric or intravenous administration in mice. Based on the pharmacokinetics data, the bioavailability of talatisamine in mice was >65.0% after oral administration, exhibiting an excellent oral absorption. SN - 1873-376X UR - https://www.unboundmedicine.com/medline/citation/31207562/Quantitative_determination_of_talatisamine_and_its_pharmacokinetics_and_bioavailability_in_mouse_plasma_by_UPLC-MS/MS L2 - https://linkinghub.elsevier.com/retrieve/pii/S1570-0232(19)30344-7 DB - PRIME DP - Unbound Medicine ER -