CN111574502B - 一种咔唑类荧光衍生试剂的设计合成及其在氟虫腈和氟虫腈代谢物检测中的应用 - Google Patents
一种咔唑类荧光衍生试剂的设计合成及其在氟虫腈和氟虫腈代谢物检测中的应用 Download PDFInfo
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Abstract
本发明涉及食品和农业安全检测领域,具体涉及一种结构新颖的咔唑类荧光衍生试剂的设计合成及其在氟虫腈和氟虫腈代谢物检测中的应用。经试验证明,本发明所设计合成的咔唑类荧光衍生试剂,具有很强的荧光强度,基于该衍生试剂所建立的柱前衍生化测定氟虫腈及其代谢物氟虫腈亚砜的HPLC‑FLD(高效液相色谱‑荧光检测)方法灵敏度高、检测限和定量限低、稳定性和重现性好,将该方法应用于鸡蛋中残留氟虫腈及其代谢物氟虫腈亚砜检测,结果准确、可靠,优于目前报道的HPLC‑MS/MS、GC‑MS方法。本发明所设计合成的咔唑类荧光衍生试剂性能优良,基于其所建立的氟虫腈及其代谢物柱前衍生化检测方法灵敏、可靠、准确,具有很好的应用前景。
Description
技术领域
本发明涉及食品和农业安全检测领域,具体涉及一种咔唑类荧光衍生试剂的设计合成及其在氟虫腈和氟虫腈代谢物检测中的应用。
背景技术
2017年8月,欧洲市场惊现氟虫腈含量超标的“毒鸡蛋”,引起了人们对食品安全的高度关注。同年,在中国香港和中国 台湾等多个地区也出现了这种“毒鸡蛋”。随着事件的发展,形势愈发严峻,“毒鸡蛋”事件波及全球,使人们陷入恐慌之中,该事件敲响预防和控制氟虫腈残留量超标的警钟,氟虫腈残留检测方法的相关研究也因此备受关注。
氟虫腈(英文名:fipronil),是法国普朗克公司于1987年研制的一种新型含氟、氯的苯基吡唑类杀虫剂,我国于1994年将其应用于农业中防治害虫。氟虫腈导致昆虫死亡的主要方式为触杀、胃毒和一定的内吸作用,其作用机制为能与害虫体内一种重要的抑制性神经递质 -γ-氨基丁酸(GABA)受体结合,使其中枢神经系统中氯离子通道关闭,从而影响中枢神经系统正常发挥作用,神经和肌肉过度兴奋,最终麻痹甚至死亡。但氟虫腈半衰期较长,难降解,对环境不友好,可在动物和人体内富集而产生毒副作用,因此对氟虫腈残留进行检测和控制是非常必要的。
目前,食品中氟虫腈及其代谢物的检测方法有高效液相色谱法(HPLC)、高效液相色谱-串联质谱法(HPLC-MS/MS)、气相色谱法 (GC)以及气相色谱-质谱联用法(GC-MS),这些检测方法各有优缺点,尚存在一定的不足,如检测灵敏度高的方法会伴有样品测前处理复杂、检验成本高、需要借助昂贵、精密的仪器、操作较为繁琐等不足,而低成本、方便、快速的检测方法则检测的灵敏度又不太好。因此,开发稳定、灵敏、选择性强、干扰小的氟虫腈及其代谢物残留的检测方法是很有必要的。
研究表明,氟虫腈结构中吡唑环上3位腈基、4位三氟甲基亚砜基及5位游离的氨基可被修饰和改造,可利用这一点来进行荧光衍生试剂的设计和合成。相比较而言,吡唑环上5位氨基更易修饰,因此针对该基团进行特异性反应生成较强荧光强度的氟虫腈衍生物是可行的。
根据上述分析,本发明合成了荧光较强、结构新颖的咔唑类荧光衍生试剂,并基于该衍生试剂建立了的柱前衍生化检测氟虫腈及其代谢物的HPLC-FLD方法。
发明内容
本发明的目的在于提供一种结构新颖的咔唑类荧光衍生试剂 (4-(2-(9-乙基-9H-咔唑-3-基)-1H-菲并[9,10-d]咪唑-1-基)丁酸,编号为L2),并提供该荧光衍生试剂的制备方法,其是以9-乙基咔唑为主要原料,通过化学合成制备得到。本发明还提供了基于上述荧光衍生试剂(L2)所建立的柱前衍生化检测氟虫腈及其代谢物的HPLC-FLD 方法。由于本发明所设计合成的咔唑类荧光衍生试剂性能优良,基于其所建立的氟虫腈及其代谢物柱前衍生化检测方法灵敏、可靠、准确,因此具有很好的应用前景。
本发明的上述目的采用以下技术方案来实现:
本发明提供一种咔唑类荧光衍生试剂(L2),包括4-(2-(9-乙基 -9H-咔唑-3-基)-1H-菲并[9,10-d]咪唑-1-基)丁酸,其结构式如下:
本发明还提供一种制备上述咔唑类荧光衍生试剂的方法,包括以下步骤:
(1)甲酰化反应:将式(II)化合物9-乙基咔唑与三氯氧磷进行反应制备得到中间体式(Ⅲ)化合物,其反应式如下:
(2)环合反应:将中间体式(Ⅲ)化合物与式(Ⅳ)化合物菲醌反应制备得到中间体式(Ⅴ)化合物,其反应式如下:
(4)卤代反应:中间体式(Ⅴ)化合物与式(Ⅵ)化合物4-溴丁酸乙酯反应制备得到式(Ⅶ)化合物,反应式如下:
(4)水解反应:式(Ⅶ)化合物与氢氧化钠反应制备得到式(I) 化合物,反应式如下:
本发明的一个优选方案,步骤(1)所述反应的反应溶剂为DMF,反应温度为98℃。
本发明的一个优选方案,步骤(2)所述反应的反应溶剂为冰醋酸,加入乙酸铵,反应温度为130℃。
本发明的一个优选方案,步骤(3)所述反应的反应溶剂为DMF,催化剂为碳酸铯,反应温度为48℃。
本发明的一个优选方案,步骤(4)所述反应的反应溶剂为甲醇水溶液,加入氢氧化钠,反应温度为30℃。
本发明还提供了一种咔唑类荧光衍生试剂在检测氟虫腈及其代谢物中的应用。
本发明的一个优选方案,所述应用具体为:采用基于具有式(I) 结构的咔唑类荧光衍生试剂建立的柱前衍生化检测氟虫腈及其代谢物的HPLC-FLD方法实现。
本发明的优选方案,基于具有式(I)结构的咔唑类荧光衍生试剂柱前衍生化氟虫腈的方法为:DCC/DMAP为催化缩合剂,二氯甲烷为溶剂,氟虫腈与荧光衍生试剂L2的摩尔浓度比为1:11,55℃水浴反应60min。
本发明的优选方案,基于具有式(I)结构的咔唑类荧光衍生试剂柱前衍生化氟虫腈所形成的产物的HPLC-FLD主要检测条件为: C18色谱柱;等度洗脱;流动相:乙腈/水(85:15);流速:1.0mL/min;λex=310nm,λem=398nm;进样量10μL;柱温40℃。
本发明的优选方案,基于具有式(I)结构的咔唑类荧光衍生试剂柱前衍生化氟虫腈代谢物的方法为:EDC/DMAP为催化缩合剂,二氯甲烷为溶剂,氟虫腈代谢物与咔唑类荧光衍生试剂L2的摩尔浓度比为1:8,在45℃水浴中反应75min。
本发明的优选方案,基于具有式(I)结构的咔唑类荧光衍生试剂柱前衍生化氟虫腈代谢所形成的产物的HPLC-FLD主要检测条件为:C18色谱柱;等度洗脱;流动相:乙腈/水=80:20;流速:1.0mL/min;λex=310nm,λem=404nm;进样量20μL;柱温40℃。
本发明的有益效果:
本发明所设计合成的具有式(I)结构的咔唑类荧光衍生试剂,结构新颖,具有很强的荧光强度,基于该衍生试剂所建立的柱前衍生化测定氟虫腈及其代谢物氟虫腈亚砜的HPLC-FLD(高效液相色谱- 荧光检测)方法灵敏度高、检测限和定量限低、稳定性和重现性好,将该方法应用于鸡蛋中残留氟虫腈及其代谢物氟虫腈亚砜检测,结果准确、可靠,优于目前报道的HPLC-MS/MS、GC-MS方法。本发明所设计合成的咔唑类荧光衍生试剂性能优良,基于其所建立的氟虫腈及其代谢物柱前衍生化检测方法灵敏、可靠、准确,具有很好的应用前景。
具体实施方式
为使本发明实施例的目的、技术方案和优点更加清楚,下面将对本发明实施例中的技术方案进行清楚、完整地描述。实施例中未注明具体条件者,按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者,均为可以通过市售购买获得的常规产品。本发明的己知的起始原料可以采用或按照本领域已知的方法来合成。
以下结合实施例对本发明的特征和性能作进一步的详细描述。
实施例1:具有式(I)结构的咔唑类荧光衍生试剂L2(4-(2-(9- 乙基-9H-咔唑-3-基)-1H-菲并[9,10-d]咪唑-1-基)丁酸)的制备
(1)具有式(Ⅲ)结构的中间体的制备
称取9-乙基咔唑(5.86g,30mmol)溶解于50mL DMF溶液中, 0℃冰浴下,逐滴加入三氯氧磷(7mL,75mmol),30min内滴加完即可。随后升温至98℃,回流搅拌,TLC检测反应进程。待反应结束后冷却至室温,加150mL水稀释,二氯甲烷萃取(3×100mL),合并有机相,无水硫酸钠干燥,脱溶,硅胶拌样,柱层析纯化分离(洗脱剂为石油醚:乙酸乙酯=15:1,v/v),制得中间体式(Ⅲ)化合物,为黄色固体,产率79.4%。结构表征数据如下:1H NMR(500MHz,DMSO)δ10.05(s,1H),8.72(s,1H),8.26(d,J=7.7Hz,1H),7.97(d,J =8.5Hz,1H),7.71(d,J=8.5Hz,1H),7.64(d,J=8.2Hz,1H),7.52(t,J =7.7Hz,1H),7.29(t,J=7.5Hz,1H),4.44(q,J=7.1Hz,2H),1.30(t,J =7.1Hz,3H).13C NMR(126MHz,DMSO)δ191.67,142.95,140.25, 128.20,126.62,126.52,123.86,122.29,122.25,120.73,120.00,109.71,109.40,37.24,13.55.HRMS(ESI)m/z[M+H]+:calcd for C15H13NO: 223.0997,found223.0978.
(2)具有式(Ⅴ)结构的中间体的制备
分别将具有式(Ⅲ)结构的中间体化合物(0.446g,2mmol)与菲醌(0.5g,2.4mmol)溶解于30mL冰醋酸溶液中,加入乙酸铵(3.08 g,40mmol),在130℃下回流搅拌反应,TLC检测反应进程。待反应结束后冷却至室温,向反应溶液加氨水调节其pH至碱性,生成大量沉淀。静置过夜,抽滤,水洗涤,真空干燥,得到的固体为具有式(Ⅴ) 结构的中间体。所制得的中间体化合物为浅黄色固体,产率89.3%。结构表征数据如下:1H NMR(500MHz,DMSO)δ9.09(d,J=0.8Hz, 1H),8.86(d,J=8.3Hz,2H),8.65(d,J=7.9Hz,2H),8.47(dd,J=8.6,1.3Hz,1H),8.29(d,J=7.7Hz,1H),7.84(d,J=8.6Hz,1H),7.76(t,J= 7.4Hz,2H),7.70–7.60(m,3H),7.52(t,J=7.6Hz,1H),7.30(t,J=7.4 Hz,1H),4.52(q,J=7.1Hz,2H),1.38(t,J=7.2Hz,3H).13C NMR(126 MHz,DMSO)δ170.22,150.47,140.11,140.05,127.39,126.94,126.16, 124.90,124.40,123.82,122.38,122.21,121.83,121.36,120.35,119.30, 118.26,109.44,59.66,37.13,13.70.HRMS(ESI)m/z[M+H]+:calcd for C29H21N3:411.1735,found 411.1700.
(3)具有式(Ⅶ)结构的中间体的制备
将具有式(Ⅴ)结构的中间体化合物(0.38g,1mmol)、4-溴丁酸乙酯(2mL,4.25mmol)溶解于30mL DMF溶液中,加入碳酸铯 (0.84g,2.5mmol),在48℃条件下搅拌反应,TLC检测反应进程。待反应结束,脱溶,硅胶拌样,柱层析纯化分离(洗脱剂为石油醚:乙酸乙酯=5:1,v/v),制得具有式(Ⅶ)结构的中间体化合物,白色固体,产率89.5%。结构表征数据如下:1H NMR(500MHz,DMSO)δ9.00 (d,J=8.2Hz,1H),8.89(d,J=8.4Hz,1H),8.64(d,J=7.4Hz,1H), 8.60(s,1H),8.54(d,J=8.2Hz,1H),8.33(d,J=7.7Hz,1H),7.90–7.82(m,2H),7.80(t,J=7.5Hz,1H),7.70(qd,J=15.0,7.1Hz,4H), 7.54(t,J=7.6Hz,1H),7.27(t,J=7.4Hz,1H),4.88(t,J=6.8Hz,2H), 4.56(q,J=6.9Hz,2H),3.69(q,J=7.1Hz,2H),2.14(d,J=6.1Hz,2H), 2.10–2.02(m,2H),1.40(t,J=7.1Hz,3H),0.90(t,J=7.1Hz,3H).13C NMR(126MHz,DMSO)δ171.75,153.83,140.04,139.82,137.30, 128.08,127.59,127.42,127.34,127.20,126.90,126.25,125.59,125.44, 124.88,124.48,123.54,122.97,122.25,122.19,121.92,121.14,120.85, 119.20,109.38,109.18,59.76,45.70,37.15,29.74,24.89,13.73, 13.67.HRMS(ESI)m/z[M+H]+:calcd for C35H31N3O2:525.2416,found 525.2335.
(4)具有式(I)结构的目标物-咔唑类荧光衍生试剂L2的制备
称取0.53g具有式(Ⅶ)结构的中间体化合物、2.4g氢氧化钠溶解于40mL甲醇/水溶液中(甲醇/水=1:1,v/v),添加适量的四氢呋喃,30℃下搅拌反应,TLC检测反应进程。待反应结束后,向反应溶液中滴加盐酸调节pH至中性,静置,抽滤,水洗涤,真空干燥,得固体为具有式(I)结构的目标产物L2。目标产物L2为白色固体,产率94.3%。结构表征数据如下:1HNMR(500MHz,DMSO)δ12.19 (bs,1H),9.08(d,J=8.3Hz,1H),8.99(d,J=8.1Hz,1H),8.79–8.68(m, 2H),8.66(d,J=8.2Hz,1H),8.31(d,J=7.7Hz,1H),7.96(q,J=8.6Hz, 2H),7.88(t,J=7.5Hz,1H),7.79(ddd,J=21.7,15.9,8.0Hz,4H),7.58 (t,J=7.7Hz,1H),7.32(t,J=7.4Hz,1H),4.92(t,J=7.1Hz,2H),4.59 (d,J=6.9Hz,2H),2.30–2.21(m,2H),2.17(dd,J=20.5,13.4Hz,2H), 1.41(t,J=7.0Hz,3H).HRMS(ESI)m/z[M+H]+:calcd forC33H27N3O2: 497.2103,found 497.2065.
实施例2:具有式(I)结构的咔唑类荧光衍生试剂柱前衍生化检测氟虫腈方法的建立
(1)氟虫腈柱前衍生化反应产物的制备
氟虫腈柱前衍生化反应如下图所示:
分别将荧光衍生试剂L2(0.16g,1mmol)和二氯甲烷(40mL)加入 100mL茄形瓶中,35℃搅拌下依次加入DMAP(0.12g,3mmol)、DCC (0.23g,1.5mmol)和氟虫腈(0.07g,0.5mmol),继续搅拌反应, TLC检测反应进程。待反应结束后,依次用20mL饱和食盐水洗2次,20mL水洗1次,水层用二氯甲烷萃取(3×50mL),无水硫酸钠干燥,脱溶,硅胶柱层析纯化分离(洗脱剂为正己烷:乙酸乙酯=3:1,v/v),得白色固体状的柱前衍生化目标产物,产率为75.8%。结构表征数据如下:1H NMR(400MHz,DMSO)δ8.99(d,J=8.1Hz,1H),8.88(d,J =8.4Hz,1H),8.64(dd,J=7.9,1.2Hz,1H),8.57(dd,J=7.8,4.8Hz, 2H),8.33(d,J=7.7Hz,1H),8.02(d,J=7.8Hz,1H),7.90–7.61(m, 7H),7.53(t,J=7.7Hz,1H),7.27(t,J=7.4Hz,1H),4.82(d,J=6.3Hz, 2H),4.54(q,J=7.0Hz,2H),3.77(t,J=11.7Hz,1H),3.26(ddd,J= 18.3,9.0,5.6Hz,1H),2.13(s,4H),1.79–0.97(m,5H).
(2)优化的氟虫腈柱前衍生化反应条件
优化后的氟虫腈柱前衍生化反应主要条件如下:以DCC/DMAP 为催化缩合剂,二氯甲烷为反应溶剂,氟虫腈与荧光衍生试剂L2的摩尔浓度比为1:11,55℃水浴中反应60min,柱前衍生化反应即完全,生成的衍生化产物为N-(3-氰基-1-(2,6-二氯-4-(三氟甲基)苯基)-4-((三氟甲基)亚磺酰基)-1H-吡唑-5-基)-4-(2-(9-乙基-9H-咔唑-3-基)-1H-菲并[9,10-d]咪唑-1-基)丁酰胺(SF2)。
(3)氟虫腈柱前衍生化产物的HPLC-FLD检测方法
氟虫腈柱前衍生化产物的HPLC-FLD检测方法如下:Symmetry C18色谱柱:4.6×250mm,5μm;柱温为40℃;流速为1.0mL/min;进样量为10μL;流动相A:100%纯乙腈,流动相B:超纯水;等度洗脱:A:85%,B:15%,时间为20min;激发波长和发射波长分别为310nm 和398nm。
结果表明:所建立的氟虫腈柱前衍生化检测方法的检测限为 0.007μg/L,定量限为0.025μg/L,精密度、稳定性及重现性的保留时间RSD<0.1%,峰面积RSD<1.5%。
实施例3:具有式(I)结构的咔唑类荧光衍生试剂柱前衍生化检测氟虫腈代谢物方法的建立
(1)氟虫腈代谢物(氟虫腈亚砜)柱前衍生化反应
氟虫腈代谢物(氟虫腈亚砜)柱前衍生化反应主要条件如下:以 EDC/DMAP为催化缩合剂,二氯甲烷为溶剂,氟虫腈亚砜与L2的摩尔浓度比为1:8,45℃水浴中反应75min,柱前衍生化反应完全,衍生产物为N-(3-氰基-1-(2,6-二氯-4-(三氟甲基)苯基)-4-((三氟甲基)硫代)-1H-吡唑-5-基)-4-(2-(9-乙基-9H-咔唑-3-基)-1H-菲并[9,10-d]咪唑-1-基)丁酰胺(DX1),具有较强的荧光强度。
(2)氟虫腈代谢物(氟虫腈亚砜)柱前衍生化HPLC-FLD检测条件
氟虫腈代谢物(氟虫腈亚砜)柱前衍生化HPLC-FLD检测主要条件如下:C18色谱柱;等度洗脱;流动相:乙腈/水(80:20);流速: 1.0mL/min;λex=310nm,λem=404nm;进样量20μL,柱温40℃。
结果表明:氟虫腈代谢物(氟虫腈亚砜)柱前衍生化HPLC-FLD 检测可在20min内完成,检测限为0.033μg/L,定量限为0.092μg/L;精密度、稳定性及重现性的保留时间RSD<0.1%,峰面积RSD<2.1%。
实施例4:具有式(I)结构的咔唑类荧光衍生试剂柱前衍生化检测鸡蛋中的残留氟虫腈
(1)鸡蛋中残留氟虫腈的提取和前处理
将样品鸡蛋去壳,以匀浆机充分混合均匀;准确称量5g鸡蛋匀浆液(精确至0.01g),置于50mL离心管,加入20mL色谱纯乙腈溶液;手动振荡混合1min,再以恒温振荡器振荡5min;随后向离心管中依次添加2g氯化钠和6g无水硫酸钠,手动振荡混合1min,4000r/min下离心10min;取其上清液待测。
(2)氟虫腈提取液柱前荧光衍生化反应的方法和条件
向2mL安瓿瓶中顺次加入300μL DCM、90μL DCC(0.1mol/L)、 90μL DMAP(0.2mol/L)、30μL氟虫腈提取液和660μL荧光衍生试剂L2(5.0×10-4mol/L),密封。充分混匀后置于55℃水浴中振荡反应 60min。随后取出冷却至室温,乙腈定容至10mL,待测。
(3)氟虫腈柱前荧光衍生化产物的HPLC-FLD检测条件
HPLC-FLD检测的主要条件如下:Symmetry C18色谱柱:4.6×250 mm,5μm;柱温为40℃;流速为1.0mL/min;进样量为10μL;等度洗脱,流动相A为100%纯乙腈,流动相B为超纯水,A相在流动相中的比例为85%,B相为15%;激发波长和发射波长分别为310nm 和398nm。
(5)鸡蛋中残留氟虫腈柱前衍生化HPLC-FLD检测方法的加标回收率、检测限和定量限
设定如下表所示的三个氟虫腈添加量进行提取、衍生化反应和检测,各个添加量平行测定三次,结果(如下表)表明,平均加标回收率均在85%以上,重现性好。鸡蛋中氟虫腈的检测限达到了0.025 μg/kg,定量限为0.082μg/kg。
(6)市售鸡蛋中残留氟虫腈的HPLC-FLD检测结果
采用上述方法,对不同地区市售鸡蛋中残留的氟虫腈进行了检测,结果如下表所示。
实施例5:具有式(I)结构的咔唑类荧光衍生试剂柱前衍生化检测鸡蛋中的残留氟虫腈代谢物
(1)鸡蛋中残留氟虫腈代谢物的提取和前处理
将样品鸡蛋去壳,以匀浆机充分混合均匀;准确称量5g鸡蛋匀浆液(精确至0.01g),置于50mL离心管,加入20mL色谱纯乙腈溶液;手动振荡混合1min,再以恒温振荡器振荡5min;随后向离心管中依次添加2g氯化钠和6g无水硫酸钠,手动振荡混合1min,4000r/min下离心10min;取其上清液待测。
(2)氟虫腈代谢物提取液柱前荧光衍生化反应的方法和条件
向2mL安瓿瓶中顺次加入600μL DCM、200μL EDC(0.1mol/L)、 200μL DMAP(0.2mol/L)、60μL氟虫腈代谢物提取液、960μL荧光衍生试剂L2(5.0×10-4mol/L),密封;充分混匀后置于45℃水浴中振荡反应75min;随后取出冷却至室温,乙腈定容至10mL,待测。
(3)氟虫腈代谢物(氟虫腈亚砜)柱前荧光衍生化产物的 HPLC-FLD检测条件
氟虫腈代谢物(氟虫腈亚砜)柱前荧光衍生化产物HPLC-FLD 检测的主要条件如下:Symmetry C18色谱柱:4.6×250mm,5μm;柱温为40℃;流速为1.0mL/min;进样量为20μL;流动相:A相为100%纯乙腈,B相为超纯水;等度洗脱:A相在流动相中的比例为80%, B相为20%;激发波长和发射波长分别为310nm和404nm。
(4)鸡蛋中残留氟虫腈代谢物(氟虫腈亚砜)柱前衍生化 HPLC-FLD检测方法的加标回收率、检测限和定量限
设定如下表所示的三个氟虫腈代谢物(氟虫腈亚砜)添加量进行提取、衍生化反应和检测,各个添加量平行测定三次,结果(如下表) 表明,平均加标回收率均在84%以上,重现性好。鸡蛋中氟虫腈亚砜的检测限达到了0.052μg/kg,定量限为0.132μg/kg。
(5)市售鸡蛋中残留氟虫腈代谢物(氟虫腈亚砜)的HPLC-FLD 检测结果
采用上述方法,对不同地区市售鸡蛋中残留的氟虫腈代谢物(氟虫腈亚砜)进行了检测,结果如下表所示。
以上所描述的实施例是本发明一部分实施例,而不是全部的实施例。本发明的实施例的详细描述并非旨在限制要求保护的本发明的范围,而是仅仅表示本发明的选定实施例。基于本发明中的实施例,本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
Claims (10)
3.根据权利要求2所述的制备方法,其特征在于,步骤(1)所述反应的反应溶剂为DMF,反应温度为98℃。
4.根据权利要求2所述的制备方法,其特征在于,步骤(2)所述反应的溶剂为冰醋酸,加入乙酸铵,反应温度为130℃。
5.根据权利要求2所述的制备方法,其特征在于,步骤(3)所述反应的溶剂为DMF,催化剂为碳酸铯,反应温度为48℃。
6.根据权利要求2所述的制备方法,其特征在于,步骤(4)所述反应的溶剂为甲醇水溶液,加入氢氧化钠,反应温度为30℃。
7.根据权利要求1所述的一种咔唑类荧光衍生试剂在检测氟虫腈及其代谢物中的应用。
8.根据权利要求7所述的一种咔唑类荧光衍生试剂在检测氟虫腈及其代谢物中的应用,其特征在于,具体为:采用基于咔唑类荧光衍生试剂建立的柱前衍生化检测氟虫腈及其代谢物的HPLC-FLD方法。
9.根据权利要求8所述的一种咔唑类荧光衍生试剂在检测氟虫腈及其代谢物中的应用,其特征在于,所述基于咔唑类荧光衍生试剂建立的柱前衍生化检测氟虫腈的HPLC-FLD方法包括:
柱前衍生化具体为:DCC/DMAP为催化缩合剂,二氯甲烷为溶剂,氟虫腈与荧光衍生试剂的摩尔浓度比为1:11,55℃水浴反应60min;
HPLC-FLD主要检测条件为:C18色谱柱;等度洗脱;流动相:乙腈/水=85:15;流速:1.0mL/min;λex=310nm,λem=398nm;进样量10μL;柱温40℃。
10.根据权利要求8所述的一种咔唑类荧光衍生试剂在检测氟虫腈及其代谢物中的应用,其特征在于,所述基于咔唑类荧光衍生试剂建立的柱前衍生化检测氟虫腈代谢物的HPLC-FLD方法包括:
柱前衍生化具体为:EDC/DMAP为催化缩合剂,二氯甲烷为溶剂,氟虫腈代谢物与咔唑类荧光衍生试剂的摩尔浓度比为1:8,在45℃水浴中反应75min;
主要检测条件为:C18色谱柱;等度洗脱;流动相:乙腈/水=80:20;流速:1.0mL/min;λex=310nm,λem=404nm;进样量20μL;柱温40℃。
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