| 红景天苷在比格犬体内绝对生物利用度研究 |
| 投稿时间：2020-12-01 修订日期：2021-01-05 点此下载全文 |
| 引用本文：黄彪,单晓菊,赵鑫,曹永兵,周婷婷,范国荣.红景天苷在比格犬体内绝对生物利用度研究[J].药学实践杂志,2021,39(1):62~67,96 |
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| 中文摘要:目的 建立比格犬血浆中的红景天苷的HPLC-MS/MS测定方法，研究红景天苷在比格犬体内的绝对生物利用度。方法 以天麻素为内标，血浆样品经蛋白沉淀后，经Symmetry RP18 (100 mm×4.6 mm, 3.5 μm)柱分离，使用体积分数0.1%甲酸溶液（A）-含0.1%甲酸和20%乙腈的甲醇溶液（B）作为流动相，进行等度洗脱（35% B），流速为0.4 ml/min，柱温40 ℃，进样量2 μl；通过电喷雾电离源(ESI)，以多反应监测(MRM)模式进行负离子检测，红景天苷、天麻素的MRM离子对分别为m/z 299.1→118.9、m/z 285.1→122.9。比格犬分别以口服和静注两种给药方式给予红景天苷原料药，在不同时间点取血，样品采用HPLC-MS/MS法测定，研究红景天苷的药动学及绝对生物利用度。结果 红景天苷的质量浓度在10～10 000 ng/ml内线性关系良好(r>0.998 6)，最低定量浓度为10.0 ng/ml。方法回收率为89.5%～91.8%，日内精密度（RSD）<9.7%，日间精密度（RSD）<7.3%。单剂量口服15 mg/kg或静注1.5 mg/kg红景天苷原料药后，cmax分别为（9 680±3 725）和（9 310±1 645）ng/ml；tmax分别为（1.25±0.67）和（0.011±0.017）h，AUC0−t分别为（20 535.4±5 200.0）和（4 646.7±720.5）ng·h/ml，AUC0-∞分别为（20 607.9±5 266.2）和（4 691.6±715.2）ng·h/ml；t1/2分别为（1.31±0.63）和（0.98 ±0.13）h。结论 该方法简便快速、灵敏可靠，可用于红景天苷体内过程研究。红景天苷在比格犬体内的绝对生物利用度为（43.9±11.2）%。 |
| 中文关键词:红景天苷 液相-串联质谱 药动学 绝对生物利用度 |
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| Absolute bioavailability of salidroside in Beagle dog |
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| Abstract:Objective To develop a HPLC-MS/MS method for the absolute bioavailability study of salidroside in Beagle dogs.Methods Gastrodin was used as internal standard. Plasma samples were treated by protein precipitation and separated by Symmetry RP18 column (100 mm×4.6 mm, 3.5 μm). 0.1% formic acid in water(A) and 0.1% formic acid in acetonitrile: methanol (20 : 80, V/V) (B) were used as the mobile phase for isocratic elution with 35% mobile phase B. The flow rate was 0.4 ml/min. Column temperature was 40 ℃. Injection volume was 2 μl. By electrospray ionization source (ESI) and multi-reaction monitoring (MRM) mode, the MRM ion pairs of salidroside and gastrodin were identified as m/z 299.1→118.9 and m/z 285.1→122.9, separately. Blood samples were collected at different time points after oral or intravenous administration of salidroside. The harvested plasma samples were analyzed by HPLC-MS/MS method to assess the pharmacokinetics and absolute bioavailability of salidroside.Results Excellent linearity(r>0.998 6) was found in the concentration range of 10−10 000 ng/ml for salidroside and the lowest quantitative concentration was 10 ng/ml. The recovery was 89.5%−91.8%. The intra-day precision (RSD) was less than 9.7%, and the inter-day precision (RSD) was less than 7.3%. After a single oral dose of 15 mg/kg or an intravenous injection of 1.5 mg/kg of salidroside, cmax was (9 680±3725) and (9 310±1 645) ng/ml; tmax was (1.25±0.67) and (0.011±0.017) h, AUC0−t was (20 535.4±5 200.0) and (4 646.7±720.5) ng·h/ml, AUC0−∞ was (20 607.9±5 266.2) and (4 691.6±715.2) ng·h/ml; t1/2 was (1.31±0.63) and (0.98±0.13) h, respectively.Conclusion The LC-MS/MS method established in this study was simple, rapid, sensitive and reliable. It meets the regulatory requirements of biological analysis for pharmacokinetic properties of salidroside in Beagle dogs. The absolute bioavailability of salidroside in Beagle dogs is (43.9±11.2)%. |
| keywords:salidroside HPLC-MS/MS pharmacokinetics absolute bioavailability |
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