CN106947021B - 聚合物整体柱、基于所述整体柱的固相萃取过滤器及其制备方法和用途 - Google Patents
聚合物整体柱、基于所述整体柱的固相萃取过滤器及其制备方法和用途 Download PDFInfo
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- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
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Abstract
本发明属于化学分离技术领域,具体涉及一种聚合物整体柱、基于所述整体柱的固相萃取过滤器及其制备方法和用途。所述聚合物由单体、交联剂、致孔剂和引发剂进行原位聚合反应得到。本发明的整体柱及固相萃取过滤器可以根据分离样品需要,选择萃取待测目标物或者杂质。与传统疏水性固相萃取材料相比,本发明的整体柱及固相萃取过滤器适用对象覆盖面更广。与传统填充型固相萃取小柱相比,能够兼顾萃取分离速度和回收率,大大提高萃取分离效率。
Description
技术领域
本发明属于化学分离技术领域,具体涉及一种聚合物整体柱、基于所述整体柱的固相萃取过滤器及其制备方法和用途。
背景技术
样品前处理是分析化学方法中不可或缺的步骤,对提高样品分析的精密度和准确度至关重要。近年来,随着有机化合物的种类不断增多,基质日益复杂多样,样品前处理技术面临着新的挑战。固相萃取技术是最为有效的样品前处理技术之一,它兼具提取和浓缩功能,并且具有有机溶剂消耗量少,萃取效率高等优点,被广泛应用于医学、食品科学、环境科学等领域的样品前处理中。传统固相萃取吸附剂大多为烷基功能化的硅胶填充柱,例如C8柱和C18柱。然而,C8/C18固相萃取柱存在如下局限性:(1)该类萃取柱为疏水性,仅适用于吸附强非极性、非极性以及中性化合物,对极性和强极性化合物萃取效果不佳;(2)在使用之前必须用甲醇等有机溶剂进行活化,使得该类柱体表面的烷基链呈伸展状态,从而能够更好地与目标化合物接触,但是活化步骤往往复杂耗时;(3)硅胶基质不能适用于碱性环境,限制了该类固相萃取柱的适用范围。
聚合物整体柱是一类由有机单体原位聚合而成的多孔连续床层,其内部结构中贯穿有大通孔。与填充柱相比,聚合物整体柱的通透性好,传质速率快,在快速分离和萃取中具有不可比拟的优势。与硅胶基质的色谱材料相比,聚合物单体选择范围广。根据单体的极性大小,研究者们可设计反相、离子交换、正相等模式整体柱。另外,聚合物整体柱耐极端pH环境能力强。正是由于上述诸多优点,固相萃取整体柱引起了人们高度重视。发展至今,多种装置已被应用于制备固相萃取整体柱,例如毛细管、微量移液枪头、PEEK(聚醚醚酮)管、不锈钢色谱柱管等。然而,固相萃取整体柱仍然存在种类单一、重复性较差、吸附容量小、操作复杂耗时等局限性,远远不能满足实际样品的分析需求。因此,发展高效、快速、高通量的新型固相萃取聚合物整体柱具有十分重要的实际应用价值。
发明内容
针对现有技术的不足,本发明提供一种聚合物,由包括下列的组分通过聚合反应制备:
1)下式(I)所示的单体:
其中,R1、R2彼此独立地选自H或无取代或任选被Ra取代的下列基团:烷基、环烷基、杂环基、烯基、炔基、芳基、杂芳基;
Y1代表-R5-R6-R7-;
R5选自化学键、-C(=O)-、-C(=S)-;
R6选自化学键、O、S、-NRb-;
R7选自化学键或无取代或任选被Ra取代的下列基团:烷基、烯基;
条件是R5、R6和R7不同时为化学键;
R3、R4彼此独立地选自无取代或任选被Ra取代的烷基;
Y2代表-R8-R9-R10-;
R8选自化学键、-C(=O)-、-C(=S)-;
R9选自化学键、O、S、-NRb-;
R10选自化学键或无取代或任选被Ra取代的下列基团:烷基、烯基;
条件是R8、R9和R10不同时为化学键;
A-代表载有负电荷的基团,例如选自-SO3 -、-COO-、-H2PO4 -;
每个Ra独立地选自H、烷基、烷氧基、烯基、炔基、环烷基、F、Cl、Br、I、OH、SH、CN、=O、NHRb、-C(O)Rb、C(O)ORb、OC(O)Rb、-CONRbRb';
每个Rb、Rb’独立地选自H、烷基、环烷基;
2)交联剂;
3)致孔剂;
4)引发剂。
作为示例性的实例,所述式(I)所示的单体可以选自例如下式所示的甲基丙烯酰乙基磺基甜菜碱:
根据本发明,所述交联剂可以选自二乙烯基苯、季戊四醇三丙烯酸酯、季戊四醇四丙烯酸酯、乙二醇二甲基丙烯酸酯、三羟甲基丙烷三丙烯酸酯、N,N-二亚甲基丙烯酰胺、N,N-1,4-二亚苯基丙烯酰胺、甲叉双丙烯酰胺。优选地,所述交联剂为甲叉双丙烯酰胺。
所述致孔剂可以选自醇类溶剂、醚类溶剂、砜类溶剂、芳烃类溶剂、卤代烃类溶剂、腈类溶剂、酯类溶剂等中的一种、两种或更多种。
例如,醇类溶剂可以选自甲醇、乙醇、丙醇、异丙醇、丁醇、戊醇、癸醇、正十二醇、环戊醇、环己醇、苯甲醇、苯乙醇;
醚类溶剂可以选自乙醚、甲基乙基醚、二丙醚、二丁醚、1,4-二氧六环、呋喃、甲基呋喃;
砜类溶剂可以选自二甲基亚砜、二甲基砜、环丁砜、2,4-二甲基环丁砜;
芳烃类溶剂可以选自甲苯、氯苯;
卤代烃类溶剂可以选自二氯甲烷、三氯甲烷、四氯化碳;
腈类溶剂可以选自乙腈;
酯类溶剂可以选自乙酸己酯、乙酸甲酯。
作为示例性的实例,所述致孔剂可以选自甲醇、二甲亚砜、正十二醇中的一种、两种或三种的混合物。作为示例性的实例,可以使用醇类溶剂和砜类溶剂的混合物作为致孔剂,其中醇类溶剂与砜类溶剂的体积比可以是10:1~1:1,例如5:1~1.5:1、3:1~1.5:1,如1.8:1。所述醇类溶剂可以选自上述醇类溶剂的混合物,例如甲醇和其他醇类溶剂(如正十二醇)的混合物。优选地,甲醇与所述其他醇类溶剂的体积比可以是3:1~1:1,例如2:1~1.1:1,如1.25:1。作为示例性的实例,可以使用甲醇、二甲亚砜和正十二醇的三元混合溶剂为致孔剂,其中甲醇、二甲亚砜和正十二醇的体积比可以是1.25:1.25:1。
所述引发剂可以选自偶氮二异丁腈、偶氮二异庚腈或其混合物。优选地,所述引发剂为偶氮二异丁腈。
优选地,本发明所述的聚合物表面具有选自下列的一种或多种官能团:极性基团、离子交换基团、非极性作用位点。
根据本发明的聚合物,优选地,所述极性基团包括但不限于选自羰基、氨基、亚氨基、酰胺基、烷氧基、环烷基、环烷基氧基、杂环基、芳基、芳基氧基、杂芳基、杂芳基氧基、硝基、羟基、卤素中的一种或多种;
根据本发明,优选地,所述离子交换基团为季铵基、磺酸基;
根据本发明,所述非极性作用位点可以为烷基基团,例如可以为甲基、乙基、丙基中的一种或多种。
本发明还提供一种整体柱,包含柱体和在柱体内的所述聚合物。
根据本发明,所述聚合物由包括上述1)、2)、3)和4)的组分在整体柱的柱体内通过原位聚合反应得到。
根据本发明,所述整体柱的柱体可以选自例如毛细管、过滤器、加样器(如微量移液器)。
本发明的整体柱可以任选地与其他分离或分析仪器,如液相色谱(LC)、高效液相色谱(HPLC)、液相色谱-质谱联用仪(LC-MS)等仪器中的一种或多种结合使用。
根据本发明的实施方案,还提供一种基于所述整体柱的毛细管、过滤器或加样器(如微量移液器)。
作为实例,所述基于整体柱的过滤器包括过滤器和在过滤器内通过原位聚合反应得到的所述聚合物。
根据本发明,所述过滤器优选为固相萃取过滤器。
本发明对于过滤器的规格和尺寸没有特别限定,本领域技术人员可以根据需要进行选择。例如,所述过滤器可以为针式过滤器,内径可以为1~50mm,如10~15mm。
根据本发明,优选地,所述整体柱或基于整体柱的过滤器,例如固相萃取过滤器可根据需要,选择萃取分离杂质或萃取分离待测目标物,从而适应不同样品的测试需求。
本发明还提供所述整体柱的制备方法,包括使上述组分1)、2)、3)和4)进行聚合反应。
根据本发明的制备方法,优选地,使上述组分在整体柱的柱体内进行原位聚合反应。
根据本发明的制备方法,可以通过如下步骤进行:
1)将上述单体、交联剂、致孔剂、引发剂混合制备聚合液;
2)将所述聚合液引入整体柱的柱体,进行聚合反应;
3)聚合反应完成后,冲洗所得的整体柱,去除残余组分。
根据本发明的制备方法,步骤1)中,所述混合可以通过搅拌或超声混合。
步骤2)中,所述聚合优选为原位聚合。优选地,可以使用注射器将所述聚合液引入过滤器。优选地,所述聚合反应在密闭条件下进行。
根据本发明,聚合反应的反应温度可以为50℃以上,优选70℃以上,例如可以在80℃下反应;反应时间可以为1h以上,例如2~24h,如12h。
根据本发明,优选地,通过将过滤器密封从而实现密闭条件。对于密封使用的材料没有限制,如可以选自生料带、封口膜、透明胶中的一种或多种。
步骤3)中,可以使用醇类溶剂,例如甲醇、乙醇或其混合物冲洗所得的整体柱。
根据本发明的实施方案,所述制备方法可通过如下步骤进行:
将上述单体、交联剂、致孔剂、引发剂组分混合均匀,利用注射器将上述聚合液引入至针式过滤器中,然后密封针式过滤器两端。待聚合反应完成后,将针式过滤器连接于注射器上,采用甲醇冲洗整体柱,去除致孔剂、未反应的单体、引发剂或交联剂。
本发明还提供一种固相萃取装置,包括所述整体柱。
作为实例,本发明提供一种固相萃取装置,包括所述基于整体柱的过滤器。根据本发明,所述固相萃取装置还可以包括注射器。优选地,所述注射器与过滤器可以根据需要连接。
本发明还提供一种固相萃取方法,包括使用所述整体柱、基于整体柱的毛细管、过滤器或加样器(如微量移液器)、或所述固相萃取装置处理样品。
所述固相萃取方法可包括如下步骤:
1)将样品溶液流经整体柱,使整体柱吸附目标组分;
2)使脱附溶剂流经过整体柱,使整体柱吸附的目标组分脱附,得到洗脱液。
根据本发明的固相萃取方法,在步骤1)中的整体柱吸附目标组分之后,还可以使用除杂溶剂洗脱杂质。
根据本发明,对于所述除杂溶剂没有任何限制,只要其可使杂质脱附且对目标组分呈惰性即可。对于所述脱附溶剂没有任何限制,只要其可使目标组分脱附即可。
优选地,所述溶剂除杂溶剂和脱附溶剂不相同,例如可彼此独立地选自水(如去离子水)或有机溶剂。所述有机溶剂可以选自醇类溶剂、醚类溶剂、砜类溶剂、芳烃类溶剂、卤代烃类溶剂、腈类溶剂、酯类溶剂中的一种或多种。
例如,醇类溶剂可以选自甲醇、乙醇、丙醇、异丙醇、丁醇、戊醇、癸醇、正十二醇、环戊醇、环己醇、苯甲醇、苯乙醇;
醚类溶剂可以选自乙醚、甲基乙基醚、二丙醚、二丁醚、1,4-二氧六环、呋喃、甲基呋喃;
砜类溶剂可以选自二甲基亚砜、二甲基砜、环丁砜、2,4-二甲基环丁砜;
芳烃类溶剂可以选自甲苯、氯苯;
卤代烃类溶剂可以选自二氯甲烷、三氯甲烷、四氯化碳;
腈类溶剂可以选自乙腈;
酯类溶剂可以选自乙酸己酯、乙酸甲酯。
任选地,步骤2)得到的洗脱液可以进一步进行分离或分析。所述分离检测包括但不限于色谱分离或分析,如液相色谱分离或分析,特别是高效液相色谱分离或分析。
根据本发明的实施方案,所述样品溶液、除杂溶剂、脱附溶剂可以使用注射器加入整体柱,例如加入基于整体柱的过滤器。
作为示例性的实施方案,所述固相萃取方法包括如下步骤:
从注射器尾端注入待萃取样品溶液,将此溶液推出后流经所述基于整体柱的固相萃取过滤器,整体柱对目标组分进行吸附;
吸附完成后,将待萃取样品溶液的溶剂推出,使用去离子水洗脱整体柱上吸附的杂质,再从注射器尾端注入甲醇,将此溶液推出后收集,所得到的甲醇洗脱液直接用于高效液相色谱分离或检测。
所述样品可以是包含例如类固醇药物的样品,所述目标组分可以是例如类固醇药物。
所述类固醇药物包括但不限于孕酮、睾丸素、醋酸甲地孕酮、醋酸环丙孕酮、左炔诺孕酮、已酸孕酮、丙酸睾丸酮中的一种或多种。
本发明还提供所述聚合物、整体柱、基于整体柱的过滤器或固相萃取装置用于固相萃取的用途。
进一步地,本发明提供所述过整体柱,特别是基于整体柱的过滤器与其他分离或分析仪器,如液相色谱(LC)、高效液相色谱(HPLC)、液相色谱-质谱联用仪(LC-MS)等仪器中的一种或多种结合用于分离或分析的用途。
术语和定义
除非另有说明,本申请说明书和权利要求书中记载的基团和术语定义,包括其作为实例的定义、示例性的定义、优选的定义、表格中记载的定义、实施例中具体化合物的定义等,可以彼此之间任意组合和结合。这样的组合和结合后的基团定义及化合物结构,应当属于本申请保护的范围内。
本发明使用的“卤素”指氟、氯、溴和碘。
本发明单独使用或用作后缀或前缀的“烷基”意在包括具有1至20个,优选1-6个碳原子(或若提供了碳原子的具体数目,则指该具体数目)的支链和直链饱和脂族烃基。例如,“C1-6烷基”表示具有1、2、3、4、5或6个碳原子的直链和支链烷基。烷基的实例包括但不限于甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、戊基和己基。
本发明使用的术语“芳基”指由5至20个碳原子构成的芳族环结构。例如:包含5、6、7和8个碳原子的芳族环结构可以是单环芳族基团例如苯基;包含8、9、10、11、12、13或14个碳原子的环结构可以是多环的例如萘基。芳环可在一个或多个环位置取代有上述那些取代基。术语“芳基”还包括具有两个或更多个环的多环环系,其中两个或更多个碳为两个相邻环所共有(所述环为“稠环”),其中至少一个环是芳族的且其它环例如可以是环烷基、环烯基、环炔基、芳基和/或杂环基。多环的实例包括但不限于2,3-二氢-1,4-苯并二氧杂环己二烯和2,3-二氢-1-苯并呋喃。
本发明使用的术语“环烷基”意在包括具有指定数目碳原子的饱和环基。这些术语可包括稠合或桥接的多环系统。环烷基在其环结构中具有3至40个碳原子。在一个实施方案中,环烷基在其环结构中具有3、4、5或6个碳原子。例如,“C3-6环烷基”表示例如环丙基、环丁基、环戊基或环己基的基团。
本发明使用的“杂芳基”指具有至少一个环杂原子(例如硫、氧或氮)的杂芳族杂环。杂芳基包括单环系统和多环系统(例如具有2、3或4个稠环)。杂芳基的实例包括但不限于吡啶基、嘧啶基、吡嗪基、哒嗪基、三嗪基、呋喃基、喹啉基、异喹啉基、噻吩基、咪唑基、噻唑基、吲哚基、吡咯基、噁唑基、苯并呋喃基、苯并噻吩基、苯并噻唑基、异噁唑基、吡唑基、三唑基、四唑基、吲唑基、1,2,4-噻二唑基、异噻唑基、苯并噻吩基、嘌呤基、咔唑基、苯并咪唑基、苯并噁唑基、氮杂苯并噁唑基、咪唑并噻唑基、苯并[1,4]二氧杂环己烯基、苯并[1,3]二氧杂环戊烯基等。在一些实施方案中,杂芳基具有3至40个碳原子且在其它实施方案中具有3至20个碳原子。在一些实施方案中,杂芳基包含3至14个、4至14个、3至7个或5至6个成环原子。在一些实施方案中,杂芳基具有1至4个、1至3个或1至2个杂原子。在一些实施方案中,杂芳基具有1个杂原子。
本发明使用的术语“杂环基”指包含3至20个原子的饱和、不饱和或部分饱和的单环、二环或三环,其中1、2、3、4或5个环原子选自氮、硫或氧,除非另有说明,其可通过碳或氮来连接,其中-CH2-基团任选被-C(O)-代替;及其中除非另有相反说明,环氮原子或环硫原子任选被氧化以形成N-氧化物或S-氧化物或环氮原子任选被季铵化;其中环中的-NH任选被乙酰基、甲酰基、甲基或甲磺酰基取代;及环任选被一个或多个卤素取代。应该理解的是,当杂环基中S原子和O原子的总数超过1时,这些杂原子不彼此相邻。若所述杂环基为二环或三环,则至少一个环可任选为杂芳族环或芳族环,条件是至少一个环是非杂芳族的。若所述杂环基为单环,则其一定不是芳族的。杂环基的实例包括但不限于哌啶基、N-乙酰基哌啶基、N-甲基哌啶基、N-甲酰基哌嗪基、N-甲磺酰基哌嗪基、高哌嗪基、哌嗪基、氮杂环丁烷基、氧杂环丁烷基、吗啉基、四氢异喹啉基、四氢喹啉基、二氢吲哚基、四氢吡喃基、二氢-2H-吡喃基、四氢呋喃基、四氢噻喃基、四氢噻喃-1-氧化物、四氢噻喃-1,1-二氧化物、1H-吡啶-2-酮和2,5-二氧代咪唑烷基。
有益效果
1.与传统疏水性固相萃取材料相比,本发明的整体柱及过滤器适用对象覆盖面更广。
2.与传统填充型固相萃取小柱相比,本发明的整体柱及过滤器传质阻力小,能够兼顾萃取分离速度和回收率,大大提高萃取分离效率。本发明过滤器的样品回收率为85%以上,例如可以为92%以上、95%以上、98%以上、100%以上,如为85%~105%。
3.与毛细管等微型萃取装置相比,本发明的过滤器规格选择范围广,不仅能够满足样品微量化的需求,而且能够提高样品吸附容量,因而更具有实际应用价值。
4.本发明的整体柱及过滤器制备方法简单,原料廉价易得,重复性良好,并且无需注射泵等复杂昂贵的装置,大大简化固相萃取分离的成本。
5.本发明的整体柱及过滤器可以根据使用需要,选择不同的组分制备得到聚合物表面具有不同官能团的整体柱及过滤器。此外,本发明的整体柱及过滤器可以根据分离样品需要,选择萃取待测目标物或者杂质。
附图说明
图1为实施例1中聚合物的制备方法示意图。
图2为实施例1基于整体柱的固相萃取针式过滤器的装置示意图。其中各附图标记含义如下:1.基于整体柱的固相萃取针式过滤器;2.注射器。
图3为实施例2基于整体柱的固相萃取过滤器对7种类固醇类药物萃取分析的高效液相色谱图。其中各附图标记含义如下:图3(A)为未经基于整体柱的固相萃取过滤器萃取分离样品的高效液相色谱图;图3(B)为经基于整体柱的固相萃取过滤器萃取分离样品的高效液相色谱图;1.左炔诺孕酮吸收峰;2.醋酸甲地孕酮吸收峰;3.醋酸环丙孕酮吸收峰;4.睾丸素吸收峰;5.孕酮吸收峰;6.丙酸睾丸酮吸收峰;7.已酸孕酮吸收峰。
具体实施方式
下文将结合具体实施例对本发明的通式化合物及其制备方法和应用做更进一步的详细说明。下列实施例仅为示例性地说明和解释本发明,而不应被解释为对本发明保护范围的限制。凡基于本发明上述内容所实现的技术均涵盖在本发明旨在保护的范围内。
除非另有说明,实施例中使用的原料和试剂均为市售商品,或可根据已知方法制备。
实施例1基于整体柱的固相萃取针式过滤器的制备
称取10.0mg偶氮二异丁腈,300mg甲基丙烯酰乙基磺基甜菜碱,300mg甲叉双丙烯酰胺,1.25mL二甲亚砜,1.25mL甲醇以及1.00mL正十二醇,超声20min使其混合均匀,通过注射器将上述聚合液注入针式过滤器(13mm i.d.)中,然后依次用生料带、封口膜、透明胶带密封针式过滤器两端,放入80℃水浴中静置12h。待聚合反应完成后(聚合反应示意图如图1所示),将针式过滤器与注射器连接(如图2),从注射器尾端注入一定量甲醇,将甲醇推出,使其流经基于整体柱的固相萃取针式过滤器以便去除致孔剂和未反应的组份。
实施例2使用基于整体柱的固相萃取过滤器对类固醇药物进行萃取分离
利用实施例1中所述的基于整体柱的固相萃取针式过滤器富集水相中微量的类固醇药物:从注射器尾端加入10mL七种微量类固醇药物的水溶液(0.550μg/mL孕酮,0.555μg/mL睾丸素,0.603μg/mL醋酸甲地孕酮,0.590μg/mL醋酸环丙孕酮,0.617μg/mL左炔诺孕酮,0.583μg/mL已酸孕酮,0.574μg/mL丙酸睾丸酮),推出此溶液,待溶液全部流出后,另外推出1mL去离子水清洗整体柱上残留的杂质,然后推出1mL甲醇,得到洗脱液。最后,采用高效液相色谱仪对收集得到的洗脱液进行分析。
色谱条件:色谱柱:XD6-C18(5μm,150mm x 4.6mm i.d.,Agilent);流动相:甲醇/水(70/30,V/V);流速:0.50mL/min,检测波长:254nm。
所得类固醇药物的高效液相色谱图如图3所示,未经本发明过滤器处理的类固醇药物溶液浓度很低,因而色谱图3(A)中类固醇药物的信号强度非常弱,经过本发明过滤器萃取分离后,洗脱溶液中七种类固醇类药物信号均明显增强(图3(B)),富集倍数约为未经本发明过滤器处理的类固醇药物信号强度的10倍,七种类固醇药物的回收率为92.3%~108%。本发明提供的基于整体柱的固相萃取针式过滤器制备方法简单,操作方便快速,具有良好的应用前景。
以上,对本发明的实施方式进行了说明。但是,本发明不限定于上述实施方式。凡在本发明的精神和原则之内,所做的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (17)
1.一种整体柱,包含柱体和在柱体内通过原位聚合反应得到的聚合物,所述柱体为过滤器,所述过滤器的内径为1-50mm,所述聚合物由包括下列的组分通过聚合反应制备:
1)下式所示的单体甲基丙烯酰乙基磺基甜菜碱:
2)交联剂甲叉双丙烯酰胺;
3)致孔剂醇类溶剂和砜类溶剂的混合物;
所述醇类溶剂与砜类溶剂的体积比是3:1~1.5:1;
所述醇类溶剂选自甲醇与正十二醇的混合物,甲醇与正十二醇的体积比是2:1~1.1:1;
所述砜类溶剂选自二甲亚砜;
4)引发剂。
2.根据权利要求1所述的整体柱,其中:所述引发剂选自偶氮二异丁腈、偶氮二异庚腈或其混合物;醇类溶剂与砜类溶剂的体积比是1.8:1。
3.根据权利要求2所述的整体柱,其中甲醇与正十二醇的体积比是1.25:1。
4.如权利要求1-3任一项所述的整体柱,其中,所述致孔剂为甲醇、二甲亚砜和正十二醇的三元混合溶剂,其中甲醇、二甲亚砜和正十二醇的体积比为1.25:1.25:1;
所述引发剂为偶氮二异丁腈。
5.如权利要求4所述的整体柱,其中,所述的聚合物表面具有下列官能团:极性基团、离子交换基团和非极性作用位点;
所述极性基团为羰基、酰胺基;
所述离子交换基团为季铵基、磺酸基;
所述非极性作用位点为甲基。
6.如权利要求1所述的整体柱,所述过滤器为针式过滤器,内径为1~50mm;所述整体柱单独使用或者与其他分离或分析仪器结合使用。
7.如权利要求6所述的整体柱,其中,所述过滤器为针式过滤器,内径为10~15mm;所述其他分离或分析仪器选自液相色谱(LC)、高效液相色谱(HPLC)、液相色谱-质谱联用仪(LC-MS)中的一种或多种。
8.如权利要求1-7任一项所述整体柱的制备方法,包括使上述组分1)、2)、3)和4)在整体柱的柱体内进行原位聚合反应。
9.如权利要求8所述的制备方法,包括:
1)将上述单体、交联剂、致孔剂、引发剂混合制备聚合液;
2)将所述聚合液引入整体柱的柱体,进行聚合反应;
3)聚合反应完成后,冲洗所得的整体柱,去除残余组分;
步骤1)中,所述混合通过搅拌或超声混合;
步骤2)中,所述聚合为原位聚合;
所述聚合反应在密闭条件下进行;
聚合反应的反应温度为50℃以上;反应时间为1h以上;
步骤3)中,使用醇类溶剂冲洗所得的整体柱。
10.如权利要求9所述的制备方法,步骤2)中,聚合反应的反应温度为70℃以上;反应时间为2~24h;
步骤3)中,使用甲醇、乙醇或其混合物冲洗所得的整体柱。
11.如权利要求8-10任一项所述的制备方法,其中所述制备方法通过如下步骤进行:
将上述单体、交联剂、致孔剂、引发剂组分混合均匀,利用注射器将上述聚合液引入至针式过滤器中,然后密封针式过滤器两端;
待聚合反应完成后,将针式过滤器连接于注射器上,采用甲醇冲洗整体柱,去除致孔剂、未反应的单体、引发剂或交联剂。
12.一种固相萃取装置,包括如权利要求1-7任一项所述的整体柱;所述固相萃取装置还包括注射器,所述注射器与过滤器根据需要连接。
13.一种固相萃取方法,包括使用如权利要求1-7任一项所述的整体柱或如权利要求12所述固相萃取装置处理样品;
所述固相萃取方法包括如下步骤:
1)将样品溶液流经整体柱,使整体柱吸附目标组分;
2)使脱附溶剂流经整体柱,使整体柱吸附的目标组分脱附,得到洗脱液。
14.如权利要求13所述的固相萃取方法,在步骤1)中的整体柱吸附目标组分之后,使用除杂溶剂洗脱杂质;
所述除杂溶剂和脱附溶剂不相同,彼此独立地选自去离子水或有机溶剂;所述有机溶剂选自醇类溶剂、醚类溶剂、砜类溶剂、芳烃类溶剂、卤代烃类溶剂、腈类溶剂、酯类溶剂中的一种或多种。
15.如权利要求14所述的固相萃取方法,将步骤2)得到的洗脱液进一步进行色谱分离或分析;
所述样品溶液、除杂溶剂、脱附溶剂使用注射器加入整体柱;
所述样品是包含类固醇药物的样品,所述类固醇药物选自孕酮、睾丸素、醋酸甲地孕酮、醋酸环丙孕酮、左炔诺孕酮、已酸孕酮、丙酸睾丸酮中的一种或多种。
16.如权利要求15所述的固相萃取方法,其中所述色谱分离或分析是高效液相色谱分离或分析;
所述目标组分是类固醇药物,所述类固醇药物选自孕酮、睾丸素、醋酸甲地孕酮、醋酸环丙孕酮、左炔诺孕酮、已酸孕酮、丙酸睾丸酮中的一种或多种。
17.如权利要求1-7任一项所述的整体柱或如权利要求12所述的固相萃取装置用于固相萃取类固醇药物的用途,所述类固醇药物选自孕酮、睾丸素、醋酸甲地孕酮、醋酸环丙孕酮、左炔诺孕酮、已酸孕酮、丙酸睾丸酮中的一种或多种。
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"Preparation and evaluation of 3 m opentubular capillary columns with a zwitterionicpolymeric porous layer for liquidchromatography";Li Peng et al.;《Journal of Separation Science》;20161031;第3738页第3.1节和Figure 1 * |
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