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目的建立测定大鼠血浆中F1含量的LC-MS/MS方法,研究F1在大鼠体内的药动学和生物利用度。方法大鼠分别经灌胃(10 mg·kg~(-1))、静脉注射(5 mg·kg~(-1))给药后,运用所建立的LC-MS/MS测定其血药浓度,选用DAS2.0软件求算药动学参数,根据灌胃、静脉注射给药药-时曲线下面积和给药剂量,计算F1的绝对生物利用度。结果灌胃和静脉注射后ACU_(0-t)分别为(27.052±10.068)和(153.878±88.777)ng·h·mL~(-1);AUC_(0-∞)分别为(31.425±9.261)和(179.054±116.794)ng·h·mL~(-1);MRT_(0-t)分别为(10.722±4.335)和(2.398±1.344)h;MRT_(0-∞)分别为(15.651±5.917)和(6.925±7.013)h;t_(1/2)分别为(4.294±1.534)和(6.052±3.633)h;ρ_(max)分别为(18.394±17.856)和(219.079±142.207)ng·mL~(-1)。F1在大鼠体内的绝对生物利用度为8.79%。结论建立了可用于测定大鼠血浆中F1的含量的方法,实验结果能指导F1进行结构优化,改善F1在体内的药动学特性,为提高F1的生物利用度提供实验依据。
Objective To establish a LC-MS / MS method for the determination of F1 content in rat plasma and study the pharmacokinetics and bioavailability of F1 in rats. Methods The rats were administered intragastrically (10 mg · kg -1) and intravenous injection of 5 mg · kg -1 (-1) respectively, and their plasma concentrations were determined by LC-MS / MS , The use of software DAS2.0 calculated pharmacokinetic parameters, according to gavage, intravenous administration of drug-time curve under the area and dose, calculate the absolute bioavailability of F1. Results The ACU_ (0-t) were (27.052 ± 10.068) and (153.878 ± 88.777) ng · h · mL -1 after intragastric and intravenous injection respectively. The AUC_ (0-∞) were (31.425 ± 9.261) And MRT_ (0-t) were (10.722 ± 4.335) and (2.398 ± 1.344) h, respectively; and MRT_ (0-∞) were (15.651 ± 5.917 and 179.054 ± 116.794 ng · h · mL -1, ) And (6.925 ± 7.013) h respectively; t 1/2 was (4.294 ± 1.534) and (6.052 ± 3.633) h respectively; ρ max was (18.394 ± 17.856) and (219.079 ± 142.207) ng · mL ~ (-1). The absolute bioavailability of F1 in rats was 8.79%. Conclusion The method for determining the content of F1 in rat plasma was established. The experimental results could guide the structural optimization of F1, improve the pharmacokinetics of F1 in vivo and provide experimental evidence for improving the bioavailability of F1.