UPLC-MS/MS分析瓜蒌子中3,29-二苯甲酰基栝楼仁三醇在大鼠体内的组织分布情况

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目的:探讨瓜蒌子的有效成分3,29-二苯甲酰基栝楼仁三醇口服给药后在大鼠体内的组织分布情况。方法:取健康SD雄性大鼠,灌胃给药后分别于时间点0.5,1,3,6 h取大鼠的胃、心、肝、脾、肺、肾组织,将组织匀浆及预处理。采用ZORBAX C18色谱柱(2.1 mm×50 mm,3.5μm),流动相含0.1%甲酸的10 mmol·L~(-1)乙酸铵溶液(A)-甲醇(B)梯度洗脱(0~0.01 min,50%A;0.01~1.0 min,50%~2%A;1.0~4.0 min,2%A;4.0~4.1 min,2%~50%A;4.1~5.0 min,50%A),流速0.5 m L·min~(-1),进样量10μL,选择电喷雾离子化三重四极杆串联质谱,以多反应监测(MRM)方式进行正离子模式检测,用于定量分析二级碎片离子分别为m/z 684.7~527.6(3,29-二苯甲酰基栝楼仁三醇)和m/z 472.4~436.4(特非那定)。结果:大鼠灌胃给药3,29-二苯甲酰基栝楼仁三醇后,在肺组织中0.5 h时药物质量分数达峰值,在心、肝、脾、肾中1.0 h时药物质量分数达峰值,而胃中在3.0 h时药物质量分数达峰值。胃和肺中药物分布较大,在胃中3.0 h时药物质量分数达最大值(405.8±114.8)ng·g~(-1);药物在肺中的分布速度最快,0.5 h时即可达到峰值(338.8±85.5)ng·g~(-1),在心、肝、脾和肾脏的分布较低,6 h时各脏器的药物质量分数已显著降低。结论:大鼠灌胃给予3,29-二苯甲酰基栝楼仁三醇后,能分布到各脏器组织,其中在胃和肺分布的浓度较高,且在3 h后仍能保持较高水平,而在心、肝、脾、肾分布浓度相对较低,这可能与该成分本身性质和作用特点有关。 OBJECTIVE: To investigate the tissue distribution in rats after orally administered 3,29-dibenzoyl triclosan, the active ingredient of melon seeds. Methods: Male Sprague-Dawley (SD) male SD rats were given intragastric administration of stomach, heart, liver, spleen, lung and kidney at 0.5, 1, 3 and 6 h after the intragastric administration. The tissues were homogenized and pretreated . The mobile phase was eluted with gradient elution of 10 mmol·L -1 ammonium acetate (A) -methanol (B) with 0.1% formic acid on a ZORBAX C18 column (2.1 mm × 50 mm, 3.5 μm) min, 50% A; 0.01-1.0 min, 50% -2% A; 1.0-4.0 min, 2% A; 4.0-4.1 min, 2-50% A; 0.5 m L · min -1, and 10 μL injection volume. Electrospray ionization triple quadrupole tandem mass spectrometry (ESI-MS / MS / MS) was used to detect the positive ions in multiple reaction monitoring (MRM) Respectively m / z 684.7 ~ 527.6 (3,29-dibenzoyl triclosan) and m / z 472.4 ~ 436.4 (terfenadine). Results: After administration of 3,29-dibenzoyl triclosan in rats, the drug mass fraction peaked at 0.5 hour in lung tissue, Up to the peak value, while the peak value of the drug mass fraction in the stomach at 3.0 h. The distribution of drugs in stomach and lungs was quite large. The drug mass fraction reached the maximum (405.8 ± 114.8) ng · g -1 at 3.0 h in the stomach, and the fastest in the lungs at 0.5 h Reached the peak of (338.8 ± 85.5) ng · g -1, with a low distribution in the heart, liver, spleen and kidney. The drug quality scores of various organs were significantly decreased at 6 h. Conclusion: After administration of 3,29-dibenzoyl triclosan, intragastric administration of 3,29-dibenzoyl triclosan could distribute to tissues of various organs, with a higher concentration in the stomach and lung, and remained stable after 3 h High level, while in the heart, liver, spleen and kidney distribution is relatively low concentration, which may be related to the nature of the composition itself and the role of characteristics.
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