CN104965035B - 固相支撑液液萃取‑色质联用筛查样本中毒性物质的方法 - Google Patents
固相支撑液液萃取‑色质联用筛查样本中毒性物质的方法 Download PDFInfo
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- CN104965035B CN104965035B CN201510201463.9A CN201510201463A CN104965035B CN 104965035 B CN104965035 B CN 104965035B CN 201510201463 A CN201510201463 A CN 201510201463A CN 104965035 B CN104965035 B CN 104965035B
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Abstract
本发明提供一种固相支撑液液萃取‑色质联用筛查样本中毒性物质的方法。该方法包括如下步骤:采用水溶性有机溶剂和去离子水的混合溶液对样本进行提取,对提取后的提取液进行离心,收取上清液并除去上清液中的有机溶剂,制得样本液;将所述样本液加入经活化的固相支撑液液萃取柱中,静置,随后采用洗脱液进行洗脱,收集洗脱液;对所述洗脱液进行色谱‑质谱分析。本发明的方法能够对样本中多种结构不同的毒性物质进行快速、有效检出,特别是一次检测即可实现对150种以上毒性物质的筛查,检测效率高,特别适用于法庭科学等领域,具有良好的实际应用价值。
Description
技术领域
本发明属于分析化学与材料科学领域,具体涉及一种固相支撑液液萃取-色质联用筛查样本中毒性物质的方法。
背景技术
法庭科学领域通常需要对新鲜器官组织、血液、体液、腐尸、腐泥等多种样本中的众多毒性物质进行检测,毒性物质范围包括农药、鼠药、医源性药物(例如安眠镇静药物、镇痛药物、麻醉药物、抗生素等)、毒品、食品添加剂、中草药等。然而,这些样本成分较为复杂,特别是所含有的油脂、色素、蛋白质、酶等杂质易对毒性物质的检测产生干扰,因此如何有效去除样本中的杂质、高效提取样本中的目标毒物成为需要研究的课题之一。
固相支撑液液萃取(supported liquid-liquid extraction,简称SLE)是以传统液液萃取原理为基础,以一种吸附性高、惰性、比表面积大的多孔填料为固相支撑体,实现相分离和目标物的萃取净化,集固相萃取技术、液液萃取技术优点于一体,具有操作简便、有机溶剂用量、快速、高通量样品处理,克服了传统液液萃取(liquid-liquid extraction,简称LLE)操作繁琐、费时、易出现乳化现象、不易实现自动化和高通量等问题。尽管SLE法已被广泛用于血浆和尿液中药物及代谢产物、酒中多酚类物质、地表水中农药残留物检测和药物成分的分离提取,然而其所针对的对象通常为某种或某类毒性物质。
此外,即便能够实现对样本中的多种结构不同的毒性物质的分离提取,由于样本的复杂性、检测目标的不确定性以及检测范围的广泛性,也很难做到有针对性地对样本中的多种毒性物质进行检测,因此样本中毒性物质的筛查至关重要。然而,各种毒性物质的理化性质、结构特点、色谱行为等性质各异,所要求的分析检测条件各异,因此如何在同一条件下对样本中的多种毒性物质进行有效分离、灵敏检测成为目前法庭科学领域毒物筛查与分析的难点及研究热点。
发明内容
本发明提供一种固相支撑液液萃取-色质联用筛查样本中毒性物质的方法,用于解决现有技术方法无法对样本中多种不同结构的毒性物质进行快速筛查等技术缺陷。
本发明提供一种采用固相支撑液液萃取-气质联用筛查样本中毒性物质的方法,包括如下步骤:
采用水溶性有机溶剂和去离子水的混合溶液对样本进行提取,对提取后的提取液进行离心,收取上清液并除去上清液中的有机溶剂,制得样本液;
将所述样本液加入经活化的固相支撑液液萃取柱中,静置,随后采用洗脱液进行洗脱,收集洗脱液;
对所述洗脱液进行色谱-质谱分析。
在一实施方式中,所述水溶性有机溶剂为丙酮,并且所述混合溶液中水溶性有机溶剂与去离子水的体积比为4∶1。本发明人经大量研究发现:采用体积比为4∶1的丙酮和去离子水的混合溶液对样本进行提取时,不仅可以有效地去除样本中的油脂、色素、蛋白等多种杂质,从而排除其对检测的不利影响,此外还能够在最大范围内使大量结构不同的目标检测物质溶出,从而在检测目标不确定、检测范围广泛时能够实现对样本中的多种毒性物质的快速筛查。混合溶液中有机溶剂体积过少可能会导致某些目标检测物质无法溶出,而体积过大不利于对后续对有机溶剂的去除,较佳的体积比为4∶1。
本发明对所述样本不作严格限制,特别是可以为器官组织、血液、体液、腐尸、腐泥等生物样本。在一实施方式中,所述样本可以为体液或血液等液态样本,并且可以控制所述混合溶液与所述样本的体积比为(1.5-2.5)∶1;此外,本发明对所述提取的温度和时间不作严格限制,其可以根据样本的种类、目标检测物质等进行确定,提取温度例如可以为室温,提取时间例如可以为1-10min。
在另一实施方式中,所述样本还可以为器官组织等固态样本,所述提取为超声波提取,超声波提取有利于固态样本中目标检测物质的释放和溶出;并且可以控制所述混合溶液与所述样本的体积/质量比为(1.5-2.5)∶1,例如样本质量为1g时,混合溶液的体积为1.5-2.5mL。此外,超声波提取的温度可以为室温,提取时间可以为20-40min。
本发明对上清液中有机溶剂的去除方式不作严格限定,例如可以采用温度为40-60℃气体流除去上清液中的有机溶剂,所述气体流为空气流或氮气流,优选为45℃的氮气流。进一步地,可以控制除去有机溶剂后的上清液的体积与样本的质量或体积比为(0.5-1)∶1,例如样本体积为2mL时,除去有机溶剂后的上清液的体积可控制在1-2mL,较佳的为1mL,从而保证无有机溶剂残留而影响目标毒性物质的检测。
本发明所述固相支撑液液萃取柱中所填装的填料可以为本领域的常规填料,例如硅藻土、中性氧化铝等,固相支撑液液萃取柱例如可以为ISOLUTE SLE萃取柱,该萃取柱在使用前可以采用甲醇进行活化。进一步地,将所述样本液的pH值调至6后加入经活化的固相支撑液液萃取柱中,所述静置的时间可以为1-10min,例如5min;此外,所述洗脱液可以为二氯甲烷、乙酸乙酯或二氯甲烷/异丙醇,优选为二氯甲烷;所述洗脱时洗脱液的流速可以为0.4-0.6mL/min,例如0.5mL/min。
在一实施方式中,所述色谱-质谱分析可以为气相色谱-质谱分析,色谱条件为:HP-5MS、HP-1MS或HP-35MS色谱柱,30m×0.25mm×0.25μm;进样口温度280℃;柱温:起始温度80℃,保持2min,以20℃/min的速率升至280℃,保持16.5min;载气为氦气,流速1mL/min,分流比20∶1;质谱条件为:传输线温度250℃;四极杆温度200℃;检测器电压1.1kV;离子化方式:EI源;溶剂延迟时间3min;扫描模式:全扫描模式,扫描质量范围50-600m/z。
研究表明:柱温起始温度过低时毒性物质的检测灵敏度降低,起始温度过高时部分毒性物质保留时间短,易受干扰而不易准确检出,较佳的起始温度为80℃。特别是,在上述气相色谱和质谱条件下进行检测有利于同时在最大范围内检出大量结构不同的目标检测物质,并且提高检测的灵敏度,从而有利于实现对样本中多种不同结构的毒性物质的快速筛查。
在另一实施方式中,所述色谱-质谱分析还可以为液相色谱-质谱分析,色谱条件为:ACQUITY UPLC HSS C18色谱柱,2.1mm×150mm,1.8μm;流动相:A为0.1%甲酸乙腈,B为5mM的甲酸铵,用0.1%的甲酸调节pH值至3.5;梯度洗脱条件:0min:13%A,87%B;10min:50%A,50%B;10.75min:95%A,5%B;12.5min:13%A,87%B;柱温:35℃;流速:0.4mL/min;质谱条件为:电离模式:电喷雾电离;毛细管电压:3.0kV;离子源温度:150℃;雾化气流速:1000L/h;扫描模式:正离子扫描,扫描质量范围50-1000m/z。
研究表明:采用乙腈作为作为有机相进行液相色谱分析时峰形良好,并且在乙腈中加入0.1%乙酸或0.1%甲酸有利于化合物的离子化,并提高离子化效率,而采用其它有机相(例如甲醇)存在峰形宽、伴有峰分叉等不良现象,不利于多种毒性物质的同时检出。此外,鉴于流动相若不使用缓冲盐体系则色谱峰形易受样品及环境的pH值影响,因此需要加入少量挥发性盐类,挥发性盐类可降低进入质谱雾化室内雾化液滴的表面张力,使目标化合物容易形成带电电荷,然而过高浓度的挥发性盐类不仅会竞争电离,从而抑制目标物的电离信号,还可能使得色谱分离时在色谱柱中出现盐析出,造成色谱柱的堵塞,柱子分离效果降低;通过对150多种毒性物质的质谱信号的影响的研究,结果表明在流动相中加入5mmol/L的甲酸铵溶液,可获得较理想的质谱响应信号,继续增大缓冲盐浓度对目标化合物的电离抑制很大,信号响应值降低。因此,本发明采用0.1%甲酸乙腈和5mM的甲酸铵作为流动相。进一步地,ACQUITY UPLC HSS C18色谱柱能够更好地实现150多种结构不同的毒性物质的同时分离,而ACQUITY μPLC BEH C18、HSTC18以及HSS C18柱的分离效果相对较差,部分毒性物质无法实现分离。
此外,在上述质谱条件中,待测物多以准分子离子峰形式存在,在一定范围内增大毛细管电压,可以优化带电离子在质量器内传输,但过大的毛细管电压会使的带电离子在质量传输的过程发生源内裂解,因此需要优化毛细管电压以使目标化合物产生最大响应信号且生成最少的碎片离子。鉴于150多种毒性物质的化学结构和性质差异较大,大部分药物采用正离子扫描模式可得较好响应值,以地西泮、阿普唑仑等物质为代表,以各电压下每种物质的信号响应值占其所有电压下响应值的比例对毛细管电压进行优化,结果发现毛细管电压与各目标化合物的极性有一定关系,对于极性较大且保留时间较短的等药物,较低的毛细管电压可获得较大的质谱响应值,而极性相对较弱且保留时间较长的药物的最大响应毛细管电压较高,综合考虑,设定毛细管电压为3.0kV。
除了毛细管电压,去溶剂雾化气流速、雾化气压力、雾化气温度等对质谱响应值也有一定的影响。在0.4mL/min的流动相流速下对不同去溶剂雾化气流速对雾化效果的影响进行研究,结果表明:过低的氮气流速去溶剂效果不佳,当氮气流速在40-60L/min时质谱响应值达到最高,因此本发明将去溶剂雾化气流速设置为50L/min;此外,不同雾化气温度对雾化效果的影响结果表明:质谱信号随着温度的上升而增强,鉴于毒性物质大多为水溶性化合物,色谱分离时使用水相比例较高,因此需要较高的雾化气温度进行雾化,结合仪器的实际情况,将雾化气温度设置为360℃。
在本发明的上述液相色谱和质谱条件下进行检测有利于同时在最大范围内检出大量结构不同的目标检测物质,并且提高检测的灵敏度,从而有利于实现对样本中多种不同结构的毒性物质的快速筛查。
本发明对所述毒性物质的具体种类及成分不作严格限制,特别是所述毒性物质可以选自农药、鼠药、医源性药物、毒品、食品添加剂和中草药中的一种或多种,尤其是所述毒性物质包括农药、鼠药、医源性药物和毒品。
进一步地,所述毒性物质选自氯苯钠敏、唑吡坦、硝西泮、扎来普隆、氯氮卓、阿米替林、阿普唑仑、艾司唑仑、三唑仑、地西泮、劳拉西泮、氯硝西泮、咪达唑仑、奥沙西泮、氯氮平、氯丙嗪、泰尔登、巴比妥、戊巴比妥、异戊巴比妥、眠尔通、烯戊巴比妥、阿米替林、多虑平、利培酮、五氟利多、马普替林、喹硫平、卡马西平、异丙嗪、三氟拉嗪、安乃近、奋乃静、萘普生、保泰松、布洛芬、非那西汀、氨基比林、阿司匹林、福尔可定、纳洛酮、纳曲酮、布比卡因、普鲁卡因、利多卡因、丁卡因、O6-单乙酰吗啡、安非他明、可待因、曲马多、哌替啶、芬氟拉明、氟哌啶醇、瑞芬太尼、双氢可待因、蒂巴因、咖啡因、可卡因、吗啡、氯胺酮、麻黄碱、伪麻黄碱、乙酰可待因、美沙酮、甲基麻黄碱、地芬诺酯、美西律、卡托普利、右美沙芬、右美托咪啶、富马酸酮替芬、甲硝唑、西米替丁、可替宁、替硝唑、硝苯地平、甲苯噻嗪、地塞米松、洛非西定、地芬尼多、舍曲林、甲基炔诺酮、那可汀、强力霉素、青霉素、罗红霉素、恩诺沙星、磺胺甲恶唑、利巴韦林、头孢呋锌钠、青霉素G钾盐、克伦特罗、齐帕特罗L、沙丁胺醇、特步他林、西玛特罗、赛布特罗、双酚A、莱克多巴胺、多巴胺、三聚氰胺、士的宁、斑蝥素、莨菪碱、秋水仙碱、山莨菪碱、丁溴东莨菪碱、乌头碱、钩吻、毒扁豆碱、阿托品、敌百虫、对硫磷、二嗪磷、甲胺磷、甲拌磷、甲基对硫磷、久效磷、乐果、马拉硫磷、三唑磷、杀扑磷、水胺硫磷、乙酰甲胺磷、毒死蜱、杀虫单、克百威、甲奈威、灭多威、速灭威、涕灭威、异丙威、仲丁威、胺菊酯、氟氯氰菊酯、高效氯氟氰菊酯、联苯菊酯、甲氰菊酯、氯氰菊酯、氰戊菊酯、溴氰菊酯、硫丹、三唑酮、丁草胺、乙草胺、异菌脲、五氯硝基苯、三氯杀螨醇、氯氟吡氧乙酸、氟磺胺草醚、特草灵、奎禾灵、4-氯苯氧乙酸、噻螨酮、三氯苯酚、硫丹醇、百菌清、敌陴、精恶唑禾草灵、莠去津、甲草胺、噻嗪酮、毒鼠强、溴敌隆、大隆、敌鼠和华法令中的一种或多种。更进一步地,所述毒性物质包括上述物质中的50种以上;特别是,所述毒性物质包括上述物质中的100种以上;尤其是,所述毒性物质包括上述物质中的150种以上。
本发明的实施,至少具有以下优势:
1、本发明的方法在采用水溶性有机溶剂和去离子水的混合溶液对样本进行提取后再利用固相支撑液液萃取柱进行萃取,不仅可以有效地去除样本中的多种杂质,从而排除其对检测的不利影响,此外还能够在最大范围内使大量结构不同的目标检测物质溶出,从而在检测目标不确定、检测范围广泛时能够实现对样本中的多种毒性物质的快速筛查。
2、本发明的方法能够实现对农药、鼠药、医源性药物、毒品、食品添加剂和中草药中的多种结构不同的毒性物质的快速、有效检出,特别是一次检测即可实现对150种以上毒性物质的筛查,检测效率高,特别适用于法庭科学等领域,具有良好的实际应用价值。
附图说明
图1为本发明实施例1的样本的GC-MS分析总离子流图。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚,下面将结合本发明的附图和实施例,对本发明实施例中的技术方案进行清楚、完整地描述,显然,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。基于本发明中的实施例,本领域普通技术人员在没有做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。
实施例中所采用的试剂、样本及仪器:
各种毒性物质标准品:来自国家标准物质研究中心、生物药品制品鉴定研究院、农药检定所、sigma公司;
血液、猪肝样本:血液来自健康人血,猪肝为普通市购;
气质联用仪:岛津GC/MS 2010,Labsolution GC/MS Solution Release2010工作站;
液质联用仪:UPLC-Xevo G2S-QTOF液相色谱-质谱联用仪,包括Mass Lynx数据处理系统(美国Waters公司)。
实施例1
1、准备标准样本
在分析天平上准确称取敌百虫、对硫磷、二嗪磷、甲胺磷、甲拌磷、甲基对硫磷、久效磷、乐果、马拉硫磷、三唑磷、杀扑磷、水胺硫磷、乙酰甲胺磷、毒死蜱、杀虫单、克百威、甲奈威、灭多威、速灭威、涕灭威、异丙威、仲丁威、胺菊酯、氟氯氰菊酯、高效氯氟氰菊酯、联苯菊酯、甲氰菊酯、氯氰菊酯、氰戊菊酯、溴氰菊酯、硫丹、三唑酮、丁草胺、乙草胺、异菌脲、五氯硝基苯、三氯杀螨醇、氯氟吡氧乙酸、氟磺胺草醚、特草灵、奎禾灵、4-氯苯氧乙酸、噻螨酮、三氯苯酚、硫丹醇、百菌清、敌陴、精恶唑禾草灵、莠去津、甲草胺、噻嗪酮标准品各25mg,置于10mL的容量瓶中,用甲醇定容,配置成2.5mg/mL标准储备液。
标准工作液的制备:分别准确量取100μL、50μL的标准储备液于1mL的玻璃试管中,再分别加入900μL、950μL甲醇定容,配制成0.1mg/mL、0.05mg/mL的标准工作液供用。
2、毒性物质的气相色谱-质谱分析
对上述标准工作液进行稀释,使各标准品的浓度均为1μg/mL,随后采用气质联用仪进行气相色谱-质谱分析,分析条件如下:
色谱条件为:
色谱柱:HP-5MS色谱柱,30m×0.25mm×0.25μm;
进样口温度:280℃;
柱温:起始温度80℃,保持2min,以20℃/min的速率升至280℃,保持16.5min;
载气为高纯氦气(纯度>99.999%),流速1mL/min,分流比20∶1;
质谱条件为:
传输线温度250℃;四极杆温度200℃;
检测器电压1.1kV;离子化方式:EI源;溶剂延迟时间3min;
扫描模式:全扫描模式,扫描质量范围50-600m/z。
采集数据,得到该样本的GC-MS分析总离子流图,如图1所示。由图1可知:本实施例的方法能够同检测出样本中的50多种结构不同的毒性物质,检测结果准确。
实施例2
向甲醇中分别加入表1中的各种毒性物质标准品,其中控制各标准品的添加浓度均为1μg/mL,随后按照实施例1分析方法进行气相色谱-质谱分析,得到各毒性物质的检测灵敏度,结果见表1。表1结果表明:本发明的气相色谱-质谱分析方法能够同时对130多种结构不同的毒性物质进行检测,检测灵敏度为0.1-10ng/μL。
表1气相色谱-质谱分析中各毒性物质的检测灵敏度
注:“-”表示未检出。
实施例3
向甲醇中分别加入表3中的各种毒性物质标准品,其中控制各标准品的添加浓度均为1μg/mL,随后采用液质联用仪进行液相色谱-质谱分析,分析条件如下:
色谱条件:
色谱柱:ACQUITYUPLC HSS C18柱,2.1mm×150mm,1.8μm;
流动相:A:0.1%甲酸乙腈,B:5mM甲酸铵(采用0.1%甲酸调节pH至3.5)
洗脱:梯度洗脱,条件见表2;
柱温:35℃;
流速:0.4mL/min;
表2液相色谱-质谱分析采用的梯度洗脱条件
时间(min) | A(%) | B(%) |
0 | 13 | 87 |
0.5 | 13 | 87 |
10 | 50 | 50 |
10.75 | 95 | 5 |
12.25 | 95 | 5 |
12.5 | 13 | 87 |
15 | 13 | 87 |
质谱条件:
离子源:电喷雾电离(ESI);
检测方式:正离子;
毛细管电压:3.0kV;
源温度:150℃;
雾化气流速:1000L/h;
高分辨扫描模式:m/z 50-1000;
采集数据,结果如表3所示。
由表3可知:
本发明的液相色谱-质谱分析方法能够同时对120多种结构不同的毒性物质进行检测。
实施例4
1、准备样本
取五份相同的血液样品各100mL,向每份血液样品中分别加入表4中的各种毒性物质标准品,其中控制各标准品的添加浓度均为1μg/mL,随后在室温下放置3周,使其高度腐败,制得样本4-1至样本4-5。
2、毒性物质的提取和分析
取上述样本4-1至样本4-5各2mL,分别加入4mL由丙酮和去离子水组成的混合溶液室温提取5min左右,其中混合溶液中丙酮与去离子水的体积比为4∶1,对提取后的提取液进行离心,收取上清液,采用45℃左右的氮气流挥干该上清液中的丙酮,剩余上清液1mL左右,随后分别调节样本4-1至样本4-5剩余上清液的pH值至3、6、7、9、11左右,制得样本液4-1至样本液4-5。
采用1mL的甲醇对2mL的ISOLUTE SLE萃取柱进行活化,随后分别对上述样本液4-1至样本液4-5进行固相支撑液液萃取和气相色谱-质谱分析,方法具体为:将某份样本液加入萃取柱中,静置5min后,采用4mL二氯甲烷进行洗脱,控制二氯甲烷洗脱的流速为0.5mL/min,收集洗脱液,采用45℃左右的氮气流挥干后,用100μL的甲醇定容,采用气质联用仪进行气相色谱-质谱分析,分析条件与实施例1相同。
采集数据,并计算各毒性物质的回收率,结果见表4。表4结果表明:pH6为固相支撑液液萃取的最佳萃取pH值。
表4各毒性物质的回收率
注:“-”表示未检出。
实施例5
1、准备样本
取五份相同的血液样品各100mL,向每份血液样品中分别加入表5中的各种毒性物质标准品,其中控制各标准品的添加浓度均为1μg/mL,随后在室温下放置3周,使其高度腐败,制得样本5-1至样本5-5。
2、毒性物质的提取和分析
取上述样本5-1至样本5-5各2mL,分别加入4mL由丙酮和去离子水组成的混合溶液室温提取5min左右,其中混合溶液中丙酮与去离子水的体积比为4∶1,对提取后的提取液进行离心,收取上清液,采用45℃左右的氮气流挥干该上清液中的丙酮,剩余上清液1mL左右,随后调节其pH值至6左右,制得样本液5-1至样本液5-5。
采用1mL的甲醇对2mL的ISOLUTE SLE萃取柱进行活化,随后分别对上述样本液5-1至样本液5-5进行固相支撑液液萃取和气相色谱-质谱分析,方法具体为:将某份样本液加入萃取柱中,静置5min后,采用4mL洗脱液进行洗脱,控制洗脱液洗脱时的流速为0.5mL/min,收集洗脱液,采用45℃左右的氮气流挥干后,用100μL的甲醇定容,采用气质联用仪进行气相色谱-质谱分析,其中,样本液5-1至样本液5-5所采用的洗脱液分别为氯仿、乙酸乙酯、二氯甲烷、二氯甲烷/异丙醇(v/v=4∶1)、氯仿/异丙醇(v/v=4∶1),各样本的气相色谱-质谱分析条件与实施例4相同,各毒性物质的回收率见表5。表5结果表明:氯仿、氯仿/异丙醇作为洗脱液时各毒性物质的回收率较低,而二氯甲烷、乙酸乙酯、二氯甲烷/异丙醇三者回收率相近,但提取的洁净程度、毒性等因素考虑,乙酸乙酯为最佳的洗脱液。
表5各毒性物质的回收率
实施例6
取五份相同的血液样品,向各份血液样品中分别加入表6中的各种毒性物质标准品,其中控制第一份至第五份血液样品中各毒性物质标准品的添加浓度均分别为1μg/mL、0.1μg/mL、50ng/mL、10ng/mL、1.0ng/mL,将各试样在室温下放置3周,使其高度腐败后,按照实施例4方法进行毒性物质的提取,调节剩余上清液的pH值至6左右后,制得样本液;按照实施例4方法对该样本液进行气相色谱-质谱分析,并计算各毒性物质的检测限,结果见表6。
实施例7
取五份相同的血液样品,向各份血液样品中分别加入表6中的各种毒性物质标准品,其中控制第一份至第五份血液样品中各毒性物质标准品的添加浓度均分别为1μg/mL、0.1μg/mL、50ng/mL、10ng/mL、1.0ng/mL,将各试样在室温下放置3周,使其高度腐败后,按照实施例4方法进行毒性物质的提取(其中调节剩余上清液的pH值至6左右),洗脱液采用45℃左右的氮气流挥干后,用300μL的甲醇定容,采用液质联用仪进行液相色谱-质谱分析,分析条件与实施例3相同,计算各毒性物质的检测限,结果见表6。
实施例8
1、准备样本
取五份相同的猪肝样品,向各份猪肝样品中分别加入表6中的各种毒性物质标准品,其中控制第一份至第五份猪肝样品中各毒性物质标准品的添加浓度均分别为1μg/g、0.1μg/g、50ng/g、10ng/g、1.0ng/g,将各样品在室温下放置3周,使其高度腐败,制得样本8-1至样本8-5。
2、毒性物质的提取和分析
取上述样本8-1至样本8-5各2g,分别加入4mL由丙酮和去离子水组成的混合溶液,室温超声波提取30min左右,其中混合溶液中丙酮与去离子水的体积比为4∶1,对提取后的提取液进行离心,收取上清液,采用45℃左右的氮气流挥干该上清液中的丙酮,剩余上清液1mL左右,随后调节其pH值至6左右,制得样本液8-1至样本液8-5。
采用1mL的甲醇对2mL的ISOLUTE SLE萃取柱进行活化,随后分别对上述样本液8-1至样本液8-5进行固相支撑液液萃取和气相色谱-质谱分析,方法具体为:将某份样本液加入萃取柱中,静置5min后,采用4mL二氯甲烷进行洗脱,控制二氯甲烷洗脱的流速为0.5mL/min,收集洗脱液,采用45℃左右的氮气流挥干后,用100μL的甲醇定容,采用气质联用仪进行气相色谱-质谱分析,分析条件与实施例4相同,计算各毒性物质的检测限,结果见表6。
实施例9
取五份相同的猪肝样品,向各份猪肝样品中分别加入表6中的各种毒性物质标准品,其中控制第一份至第五份猪肝样品中各毒性物质标准品的添加浓度均分别为1μg/g、0.1μg/g、50ng/g、10ng/g、1.0ng/g,将各试样在室温下放置3周,使其高度腐败后,按照实施例8方法进行毒性物质的提取,洗脱液采用45℃左右的氮气流挥干后,用300μL的甲醇定容,采用液质联用仪进行液相色谱-质谱分析,分析条件与实施例3相同,计算各毒性物质的检测限,结果见表6。
表6各毒性物质的检测限
实施例10
除采用甲醇和去离子水组成的混合溶液进行提取,混合溶液中甲醇与去离子水的体积比为4∶1之外,其余与实施例4相同,结果表明:采用甲醇和去离子水组成的混合溶液对样本进行提取时,毒物检出灵敏度低、杂质干扰大,毒物种类减少,部分毒性物质(例如2,4-滴丁酯、阿福特罗等)无法提取出来,样本中毒性物质的检出范围相比实施例4有所缩小。
实施例11
除色谱条件中,柱温:起始温度100℃,保持2min,以10℃/min的速率升至280℃,保持16.5min之外,其余与实施例4相同,结果表明:部分毒性物质(例如灭多威、甲基苯丙胺、敌敌畏、甲胺磷等)保留时间在4分钟以内,检测易受到干扰而不易检出,样本中毒性物质的检出范围相比实施例4有所缩小。
最后应说明的是:以上各实施例仅用以说明本发明的技术方案,而非对其限制;尽管参照前述各实施例对本发明进行了详细的说明,本领域的普通技术人员应当理解:其依然可以对前述各实施例所记载的技术方案进行修改,或者对其中部分或者全部技术特征进行等同替换;而这些修改或者替换,并不使相应技术方案的本质脱离本发明各实施例技术方案的范围。
Claims (8)
1.一种固相支撑液液萃取-色质联用筛查样本中毒性物质的方法,其特征在于,包括如下步骤:
采用水溶性有机溶剂和去离子水的混合溶液对样本进行提取,对提取后的提取液进行离心,收取上清液并除去上清液中的有机溶剂,制得样本液;
将所述样本液加入经活化的固相支撑液液萃取柱中,静置,随后采用洗脱液进行洗脱,收集洗脱液;
对所述洗脱液进行色谱-质谱分析,
其中,所述色谱-质谱分析为液相色谱-质谱分析,色谱条件为:ACQUITY UPLC HSS C18色谱柱,2.1mm×150mm,1.8μm;流动相:A为0.1%甲酸乙腈,B为5mM的甲酸铵,用0.1%的甲酸调节pH值至3.5;梯度洗脱条件:0min:13%A,87%B;10min:50%A,50%B;10.75min:95%A,5%B;12.5min:13%A,87%B;柱温:35℃;流速:0.4mL/min;质谱条件为:电离模式:电喷雾电离;毛细管电压:3.0kV;离子源温度:150℃;雾化气流速:1000L/h;扫描模式:正离子扫描,扫描质量范围50-1000m/z。
2.根据权利要求1所述的方法,其特征在于,所述水溶性有机溶剂为丙酮,并且所述混合溶液中水溶性有机溶剂与去离子水的体积比为4:1。
3.根据权利要求1或2所述的方法,其特征在于,所述样本为体液或血液,并且控制所述混合溶液与所述样本的体积比为(1.5-2.5):1,所述提取的温度为室温,提取时间为1-10min。
4.根据权利要求1或2所述的方法,其特征在于,所述样本为器官组织,所述提取为超声波提取,并且控制所述混合溶液与所述样本的体积/质量比为(1.5-2.5):1,所述提取的温度为室温,提取时间为20-40min。
5.根据权利要求1或2所述的方法,其特征在于,采用温度为40-60℃气体流除去上清液中的有机溶剂,所述气体流为空气流或氮气流。
6.根据权利要求1或2所述的方法,其特征在于,所述固相支撑液液萃取柱中所填装的填料为硅藻土或中性氧化铝,所述洗脱液为二氯甲烷、乙酸乙酯或二氯甲烷/异丙醇,所述洗脱时洗脱液的流速为0.4-0.6mL/min。
7.根据权利要求1或2所述的方法,其特征在于,所述毒性物质选自农药、鼠药、医源性药物、毒品、食品添加剂和中草药中的一种或多种。
8.根据权利要求7所述的方法,其特征在于,所述毒性物质选自氯苯钠敏、唑吡坦、硝西泮、扎来普隆、氯氮卓、阿米替林、阿普唑仑、艾司唑仑、三唑仑、地西泮、劳拉西泮、氯硝西泮、咪达唑仑、奥沙西泮、氯氮平、氯丙嗪、泰尔登、巴比妥、戊巴比妥、异戊巴比妥、眠尔通、烯戊巴比妥、阿米替林、多虑平、利培酮、五氟利多、马普替林、喹硫平、卡马西平、异丙嗪、三氟拉嗪、安乃近、奋乃静、萘普生、保泰松、布洛芬、非那西汀、氨基比林、阿司匹林、福尔可定、纳洛酮、纳曲酮、布比卡因、普鲁卡因、利多卡因、丁卡因、O6-单乙酰吗啡、安非他明、可待因、曲马多、哌替啶、芬氟拉明、氟哌啶醇、瑞芬太尼、双氢可待因、蒂巴因、咖啡因、可卡因、吗啡、氯胺酮、麻黄碱、伪麻黄碱、乙酰可待因、美沙酮、甲基麻黄碱、地芬诺酯、美西律、卡托普利、右美沙芬、右美托咪啶、富马酸酮替芬、甲硝唑、西米替丁、可替宁、替硝唑、硝苯地平、甲苯噻嗪、地塞米松、洛非西定、地芬尼多、舍曲林、甲基炔诺酮、那可汀、强力霉素、青霉素、罗红霉素、恩诺沙星、磺胺甲恶唑、利巴韦林、头孢呋锌钠、青霉素G钾盐、克伦特罗、齐帕特罗L、沙丁胺醇、特步他林、西玛特罗、赛布特罗、双酚A、莱克多巴胺、多巴胺、三聚氰胺、士的宁、斑蝥素、莨菪碱、秋水仙碱、山莨菪碱、丁溴东莨菪碱、乌头碱、钩吻、毒扁豆碱、阿托品、敌百虫、对硫磷、二嗪磷、甲胺磷、甲拌磷、甲基对硫磷、久效磷、乐果、马拉硫磷、三唑磷、杀扑磷、水胺硫磷、乙酰甲胺磷、毒死蜱、杀虫单、克百威、甲奈威、灭多威、速灭威、涕灭威、异丙威、仲丁威、胺菊酯、氟氯氰菊酯、高效氯氟氰菊酯、联苯菊酯、甲氰菊酯、氯氰菊酯、氰戊菊酯、溴氰菊酯、硫丹、三唑酮、丁草胺、乙草胺、异菌脲、五氯硝基苯、三氯杀螨醇、氯氟吡氧乙酸、氟磺胺草醚、特草灵、奎禾灵、4-氯苯氧乙酸、噻螨酮、三氯苯酚、硫丹醇、百菌清、敌陴、精恶唑禾草灵、莠去津、甲草胺、噻嗪酮、毒鼠强、溴敌隆、大隆、敌鼠和华法令中的一种或多种。
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