Pharmacokinetic Study of HRO761 in Rats by Liquid Chromatography Combined With Electrospray Ionization Tandem Mass Spectrometry

IF 1.8 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Jie Shen, Liye Ge, Guowei Jiang, Yongjun Meng, Weina Ma
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引用次数: 0

Abstract

A simple and sensitive liquid chromatography tandem mass spectrometry method was established and validated for determination of HRO761 in rat plasma. After prepared by protein precipitation with acetonitrile, HRO761 and internal standard were separated on a Waters BEH C18 column using acetonitrile containing 0.1% formic acid and 0.1% formic acid in water as mobile phase by gradient elution. The method showed excellent linearity over the range of 5–5000 ng/mL with acceptable intraday and interday precision, accuracy, matrix effect, and recovery. The stability assay indicated that HRO761 was stable during the sample acquisition, preparation, and storage. The method was applied to pharmacokinetic study of HRO761 in rats. The result suggested that after intravenous administration at dose of 1 mg/kg, HRO761 was quickly eliminated from the plasma with the elimination half-life of 1.9 h. After oral administration at doses of 5, 10, and 20 mg/kg, HRO761 was quickly absorbed into plasma and reach the peak concentration (Cmax) of 2598.1–9379.2 ng/mL at 1.0–4.0 h. The exposure increased proportionally with the dose. The oral bioavailability was 79.0%–99.1% over the range of 5–20 mg/kg. This study provides useful information for its further development in clinic.

液相色谱-电喷雾串联质谱联用研究HRO761在大鼠体内的药动学
建立了一种简便、灵敏的液相色谱串联质谱法测定大鼠血浆中HRO761的方法。用乙腈沉淀蛋白制备后,以含有0.1%甲酸的乙腈和0.1%甲酸水溶液为流动相,梯度洗脱,在Waters BEH C18色谱柱上分离HRO761和内标。该方法在5 - 5000ng /mL范围内线性良好,日内、日间精密度、准确度、基质效应和回收率均可接受。稳定性分析表明,HRO761在样品采集、制备和储存过程中都是稳定的。将该方法应用于HRO761在大鼠体内的药动学研究。结果表明,以1 mg/kg剂量静脉给药后,HRO761可迅速从血浆中消除,消除半衰期为1.9 h。经5、10、20 mg/kg剂量口服后,HRO761迅速被血浆吸收,并在1.0 ~ 4.0 h达到峰值浓度(Cmax) 2598.1 ~ 9379.2 ng/mL。暴露量随剂量成比例增加。在5 ~ 20 mg/kg范围内,口服生物利用度为79.0% ~ 99.1%。本研究为其在临床的进一步发展提供了有益的信息。
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来源期刊
Biomedical Chromatography
Biomedical Chromatography 生物-分析化学
CiteScore
3.60
自引率
5.60%
发文量
268
审稿时长
2.3 months
期刊介绍: Biomedical Chromatography is devoted to the publication of original papers on the applications of chromatography and allied techniques in the biological and medical sciences. Research papers and review articles cover the methods and techniques relevant to the separation, identification and determination of substances in biochemistry, biotechnology, molecular biology, cell biology, clinical chemistry, pharmacology and related disciplines. These include the analysis of body fluids, cells and tissues, purification of biologically important compounds, pharmaco-kinetics and sequencing methods using HPLC, GC, HPLC-MS, TLC, paper chromatography, affinity chromatography, gel filtration, electrophoresis and related techniques.
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