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超高效液相色谱-三重四极杆质谱联用测定蛇床子素B:应用于蛇床子素B在大鼠血浆中的药代动力学研究

Determination of sparstolonin B by ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry: application to pharmacokinetic study of sparstolonin B in rat plasma.

作者信息

Zou Nuo-Shu, Liang Qiao-Li, Li Ping, Liu Jie, Liu Xiao, Kang An, Deng Hai-Shan

机构信息

Nanjing University of Chinese Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing, 210023, China.

Nanjing University of Chinese Medicine, Jiangsu Key Laboratory of Chinese Medicine Processing, Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, Nanjing, 210023, China.

出版信息

Biomed Chromatogr. 2015 Oct;29(10):1486-91. doi: 10.1002/bmc.3447. Epub 2015 Mar 2.

DOI:10.1002/bmc.3447
PMID:25731641
Abstract

Sparstolonin B (SsnB), a spontaneous isocoumarin compound isolated from the tuber of Scirpus yagara Ohwi. (Cyperaceae), possesses potent anti-inflammatory and antitumor activity. In the present study, a rapid and simple UHPLC/MS/MS method for determination of SsnB in rat plasma was developed and validated. Plasma samples were pretreated by liquid-liquid extraction with ethyl acetate containing rhein as an internal standard and separated on a C18 column at 35 °C, with a gradient mobile phase consisting of acetonitrile and water containing 0.2% (v/v) formic acid within 2.1 min. MS/MS detection was accomplished in multiple reaction monitoring mode with negative electrospray ionization. The precursor-product ion transitions were m/z 266.9 M-H  → m/z 211.0 for SsnB and m/z 283.2 M-H  → m/z 239.0 for IS. The intra- and inter-day precision (RSD) was <8.98% and the accuracy (RE) ranged from -7.40 to 4.50%. The extraction recoveries ranged from 96.28 to 97.30%. The pharmacokinetic parameters were calculated using Win Nonlin53 software. The absolute bioavailability of SsnB was estimated to be 6.98%. The proposed method was successfully applied to a pharmacokinetic study of SsnB in rats after intravenous administration with a dose of 0.5 mg/kg and oral administration at a dose of 5 mg/kg.

摘要

水蓼二醛(SsnB)是一种从水葱(莎草科)块茎中分离出的天然异香豆素化合物,具有强大的抗炎和抗肿瘤活性。在本研究中,开发并验证了一种快速简便的超高效液相色谱/串联质谱法(UHPLC/MS/MS)用于测定大鼠血浆中的SsnB。血浆样品采用含大黄酸作为内标的乙酸乙酯液-液萃取法进行预处理,并在35℃下于C18柱上分离,流动相为乙腈和含0.2%(v/v)甲酸的水,在2.1分钟内进行梯度洗脱。采用负电喷雾电离在多反应监测模式下完成MS/MS检测。SsnB的前体-产物离子跃迁为m/z 266.9 M-H  → m/z 211.0,内标的前体-产物离子跃迁为m/z 283.2 M-H  → m/z 239.0。日内和日间精密度(RSD)<8.98%,准确度(RE)范围为-7.40至4.50%。萃取回收率范围为96.28至97.30%。使用Win Nonlin53软件计算药代动力学参数。SsnB的绝对生物利用度估计为6.98%。所建立的方法成功应用于大鼠静脉注射0.5 mg/kg剂量和口服5 mg/kg剂量后SsnB的药代动力学研究。

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