中国血吸虫病防治杂志 ›› 2018, Vol. 30 ›› Issue (3): 317-321,345.

• 论著 • 上一篇    下一篇

新型抗血吸虫杂环化合物UPLC?QTOF?MS 分析方法的建立

叶扬|惠人杰|冯柏年*   

  1. 江南大学药学院药物合成与分析实验室(无锡214000)
  • 出版日期:2018-07-02 发布日期:2018-07-02
  • 通讯作者: 冯柏年
  • 作者简介:叶扬|女|硕士研究生。研究方向:药物分析

Development of a novel method for UPLC-QTOF-MS analysis of anti-schistosomiasis heterocyclic compounds

YE Yang| HUI Ren-jie| FENG Bai-nian*   

  1. Laboratory of Drug Synthesis and Analysis| School of Pharmacy| Jiangnan University| Wuxi 214000| China
  • Online:2018-07-02 Published:2018-07-02
  • Contact: FENG Bai?nian

摘要: 目的 建立新型抗血吸虫杂环化合物噁二唑?2?氧化物杂环类似物F?2015?14的超高效液相色谱?四级杆飞行时间质谱(UPLC?QTOF?MS)分析方法。方法 小鼠血浆及组织样品经乙酸乙酯萃取,以C18色谱柱进行色谱分离,再经流动相为10%乙腈?0.1%(体积分数)甲酸溶液,梯度洗脱分离,采用超高效液相色谱?四级杆飞行时间质谱检测F?2015?14。 结果 小鼠血浆中F?2015?14在12.5 ~ 250 mg/mL范围内线性关系良好,相关系数为0.990,检出限为8.8 mg /mL;小鼠肝匀浆中F?2015?14在12.5 ~ 250 mg/mL范围内线性关系良好,相关系数为0.992,检出限为5.6 mg/mL。在加样量为12.5 mg/mL的小鼠血浆和肝匀浆样品中,UPLC?QTOF?MS的准确度和基质效应均在80% ~ 120%,日间、日内精密度均< 20%;在加样量为100、200 mg/mL的小鼠血浆和肝匀浆样品中,UPLC?QTOF?MS的准确度和基质效应均在85% ~ 115%,日间、日内精密度均< 15%。 结论 UPLC?QTOF?MS检测新型抗血吸虫杂环化合物噁二唑?2?氧化物(F?2015?14)具有较好的灵敏度及重复性,为抗血吸虫新药的研发奠定了基础。

关键词: 血吸虫病;噁二唑?2?氧化物;杂环化合物;超高效液相色谱?四级杆飞行时间质谱法

Abstract: Objective To develop an ultra?performance liquid chromatography/quadrupole?time of flight mass spectrometry (UPLC?QTOF?MS) method for the determination of an oxadiazole?2?oxide heterocyclic compound F?2015?14. Methods Mouse plasma and liver homogenate specimens were extracted with ethyl acetate and chromatographed on a Waters CORTECS column (C18, 1.6 μm, 2.1 mm × 150 mm) by using a mobile phase of 10% acetonitrile?0.1% formic acid with by a volume fractionation by gradient elution. Then, UPLC?QTOF?MS was performed to determine F?2015?14 in mouse plasma and liver homogenate specimens. Results The linearity of F?2015?14 in plasma ranged from 12.5 to 250 mg/mL with a correlation coefficient of 0.990 and a detection limit of 8.8 mg/mL. F?2015?14 in liver homogenates ranged from 12.5 to 250 mg/mL. The linearity was good with a correlation coefficient of 0.992 and a limit of detection of 5.6 mg/mL. If the concentration of plasma and liver homogenate specimens was 12.5 mg/mL, the accuracy and the matrix effect were 80% to 120%, and the inter?day and intra?day precision was within 20%. If the concentrations of plasma and liver homogenate specimens were 100 mg/mL and 200 mg/mL, the accuracy and the matrix effect were 85% to 115%, and the inter?day and intra?day precision was within 15%. Conclusion The UPLC?QTOF?MS established in this study has a high sensitivity and good reproducibility for the determination of F?2015?14, which provides bases for the development of novel anti?schistosomiasis drugs.

Key words: Schistosomiasis; Oxadiazole?2?oxide; Heterocyclic compound; Ultra?performance liquid chromatography/quadrupole?time of flight mass spectrometry

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