新型抗血吸虫杂环化合物UPLC-QTOF-MS分析方法的建立  

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

作　　者：叶扬 惠人杰 冯柏年 YE Yang, HUI Ren-fie, FENG Bai-nian(Laboratory of Drug Synthesis and Analysis, School of Pharmacy, Jiangnan University, Wuxi 214000, Chin)

机构地区：[1]江南大学药学院药物合成与分析实验室,无锡214000

出　　处：《中国血吸虫病防治杂志》2018年第3期317-321,345,共6页Chinese Journal of Schistosomiasis Control

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12.5~250mg/mL范围内线性关系良好,相关系数为0.990,检出限为8.8mg/mL;小鼠肝匀浆中F-2015-14在12.5~250mg/mL范围内线性关系良好,相关系数为0.992,检出限为5.6mg/mL。在加样量为12.5mg/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、200mg/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。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 μm） 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 speci- mens. Results The linearity of F-2015-14 in plasma ranged from 12.5 to 250 μg/mL with a correlation coefficient of 0.990 and a detection limit of 8.8 μg/mL. F-2015-14 in liver homogenates ranged from 12.5 to 250 μg/mL. The linearity was good with a cor- relation coefficient of 0.992 and a limit of detection of 5.6 μg/mL. If the concentration of plasma and liver homogenate specimens was 12.5 μg/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 μg/mL and 200 μg/mL, the accuracy and the ma- trix effect were 85% to 115%, and the inter-day and intra-day precision was within 15%. Conclusion The UPLC-QTOF-MS es- tablished 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.

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 

分 类 号：R532.21[医药卫生—内科学]