夏 天 刘德鼎 石力夫 胡晋红. LC-MS/MS法研究氢溴酸东莨菪碱口腔速崩微囊片在比格犬体内的药代动力学J. 药学学报, 2011,46(8): 951-954.
引用本文: 夏 天 刘德鼎 石力夫 胡晋红. LC-MS/MS法研究氢溴酸东莨菪碱口腔速崩微囊片在比格犬体内的药代动力学J. 药学学报, 2011,46(8): 951-954.
JIA Tian, Liu-De-Ding, Dan-Li-Fu, Hu-Jin-Gong. Pharmacokinetics of scopolamine hydrobromide oral disintegrative microencapsule tablets in Beagle dogs determined with LC-MS/MSJ. 药学学报, 2011,46(8): 951-954.
Citation: JIA Tian, Liu-De-Ding, Dan-Li-Fu, Hu-Jin-Gong. Pharmacokinetics of scopolamine hydrobromide oral disintegrative microencapsule tablets in Beagle dogs determined with LC-MS/MSJ. 药学学报, 2011,46(8): 951-954.

LC-MS/MS法研究氢溴酸东莨菪碱口腔速崩微囊片在比格犬体内的药代动力学

Pharmacokinetics of scopolamine hydrobromide oral disintegrative microencapsule tablets in Beagle dogs determined with LC-MS/MS

  • 摘要:

    研究氢溴酸东莨菪碱口腔速崩微囊片在比格犬体内的药代动力学和生物等效性。液相色谱分离采用C18 (100 mm × 3.0 mm, 3.5 μm), 甲醇 − 2 mmol·L−1甲酸铵溶液 (2575) 为流动相; 质谱检测采用ESI离子源, 正离子MRM方式检测。将6只比格犬随机分成2, 分别单剂量灌服氢溴酸东莨菪碱口腔速崩微囊片 (受试制剂) 和氢溴酸东莨菪碱普通片 (参比制剂) 0.6 mg, 定时采集血样, 测定比格犬体内的血药浓度并计算药代动力学参数。受试制剂和参比制剂的Cmax分别为 (8.16 ± 0.67)(3.54 ± 0.64) ng·mL−1; t1/2分别为 (2.83 ± 0.45)(3.85 ± 0.82) h; tmax分别为 (1.25 ± 0.27)(0.42 ± 0.09) h; AUC0−12 h分别为 (25.06 ± 3.75)(9.59 ± 1.02) h·ng·mL−1; AUC0−∞分别为 (26.30 ± 3.92)(10.80 ± 1.45) h·ng·mL−1; MRT0−12 h分别为 (3.38 ± 0.34)(3.86 ± 0.26) h; MRT0−∞分别为 (3.98 ± 0.63)(5.37 ± 1.00) h。受试制剂和参比制剂在AUC和吸收速率方面具有显著差异, 受试制剂的生物利用度明显高于参比制剂。

     

    Abstract:

    The study aims to elucidate the characteristics of pharmacokinetics of scopolamine hydrobromide oral disintegrative microencapsule tablets in healthy Beagle dogs.  Chromatographic separation was performed on a C18 column (100 mm × 3.0 mm, 3.5 μm) with methanol 2 mmol·L−1 ammonium formate (2575) as the mobile phase.  A trip-quadrupole tandem mass spectrum with the electrospray ionization (ESI) source was applied and positive ion multiple reaction monitoring mode was operated.  Six Beagle dogs were randomly devided into two groups.  They received oral single dose of scopolamine hydrobromide oral disintegrative microencapsule tablets 0.6 mg (test tablet) or scopolamine hydrobromide normal tablets (reference tablet).  Plasma samples were collected at designed time.  Plasma concentration of scopolamine hydrobromide was determined by LC-MS/MS and pharmacokinetic parameters were calculated.  The pharmacokinetic parameters of test tablet vs reference tablet were as follows: Cmax: (8.16 ± 0.67) ng·mL−1 vs (3.54 ± 0.64) ng·mL−1; t1/2: (2.83 ± 0.45) h vs (3.85 ± 0.82) h; tmax: (1.25 ± 0.27) h vs (0.42 ± 0.09) h; AUC0−12 h: (25.06 ± 3.75) h·ng·mL−1 vs (9.59 ± 1.02) h·ng·mL−1; AUC0−∞: (26.30 ± 3.92) h·ng·mL−1 vs (10.80 ± 1.45) h·ng·mL−1; MRT0−12 h: (3.38 ± 0.34) h vs (3.86 ± 0.26) h; MRT0−∞: (3.98 ± 0.63) h vs (5.37 ± 1.00) h.  The absorption rate and AUC of test tablet is different from that of reference tablet.  The bioavailability of test tablet is better than those of reference tablet.

     

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