CN109100437A - 仲胺类抗抑郁药物的质谱检测方法 - Google Patents
仲胺类抗抑郁药物的质谱检测方法 Download PDFInfo
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Abstract
本发明公开了一种仲胺类抗抑郁药物的质谱检测方法,其方法为:(1)所述抗抑郁药样品加入亚硝酸钠溶液进行衍生反应,萃取得到衍生样品溶液;(2)所述衍生样品溶液通过质谱全扫描,选择性离子分别为:氟西汀104.1,117.1,177.1;去甲替林219.1,232.1,204.1;马普替林248.2,203.1,276.1,178.1;帕罗西汀358.2,138.0,109.0,329.2。本方法将目标物转化为极性较小的脂溶性物质再提取检测,利于提取和气相检测,大大提高了检测灵敏度;与现有衍生方法(硅烷化或酯化)比较,本方法具有副反应少的优点;本发明操作过程都近似为小型液液萃取过程,具有简单快速特点。
Description
技术领域
本发明涉及一种药物检测方法,尤其是一种仲胺类抗抑郁药物的质谱检测方法。
背景技术
抑郁症是一种情感障碍性精神疾病,以显著而持久的心境低落为主要特征,以及思维迟缓、失眠、食欲不振、自我认同感较低等症状,严重者可出现自杀念头和行为。随着抑郁症的高患病率,抗抑郁药物的使用也加速上升。
抗抑郁药自20世纪50年代问世至今不断的发展壮大,其作用机制主要为:单胺氧化酶的抑制、神经递质再摄取的抑制和受体介导的作用机制。第一代抗抑郁药包括单胺氧化酶抑制剂(MAGI)和三环类抗抑郁药(TCA)。MA01主要有环苯丙胺和苯乙脐;TCA主要有丙咪嗓、阿米替林、多虑平、氯米帕明等。这些药物由于明显的副作用,且对心脏功能有一定的损害,因此在临床上渐渐被第二代抗抑郁药所取代。第二代抗抑郁药又称为新型抗抑郁药,按作用机理不同可分为:选择性单胺氧化酶抑制(SMAOI)、选择性5-经色胺(5-HT)再摄取抑制剂(SSRI)、选择性去甲肾上腺素(NE)再摄取抑制剂(SNRI)、选择性5-轻色胺和去甲肾上腺素双重再摄取抑制剂(S SNRI)、NE能和特异性5-HT能抗抑郁剂(NaSSA)以及NE和多巴胺(DA)回收抑制剂(NDRI)等。它们的代表药物分别如下,SMA01:吗氯贝胺;S SRI:氟西汀、诺氟西汀、帕罗西汀、氟伏沙明、舍曲林、西酞普兰、艾司西酞普兰及曲哇酮等;SNRT:瑞波西汀、米安舍林、马普替林、去甲替林等。
抗抑郁药在治疗疾病的同时,也会因用药不当而产生毒性,有一定毒副作用,同时,有些药物不能同时服用。心血疾病患者不慎使用可能引起不适甚至中毒。也有将其加人中成药和保健食品致人死亡案件的报道。急性中毒可出现口干、便秘、尿潴留、视力模糊、眼内压升高、乏力、心力衰竭等症状,最后心肌梗塞,呼吸抑制而死亡。此外,在一些案例中如服用抗抑郁药等精神类药物后驾驶,利用抗抑郁药等实施暴力犯罪等情况下,需要对抗抑郁药物进行分析,因此需要建立可靠灵敏的方法对生物基质中的抗抑郁药进行快速的定性定量分析,以满足临床和法医鉴定工作的需求。
对于抗抑郁药物的分析检测主要有HELC、LC-MS、GC-MS方法,涉及到的生物样品主要为血浆、尿液、全血等。这些方法使用的生物样品前处理手段主要为固相萃取,存在操作麻烦,耗时较长,有机溶剂消耗较多等缺点,且大部分文献报道为一种或两三种抗抑郁药同时检测。
发明内容
本发明要解决的技术问题是提供一种简单、快速的仲胺类抗抑郁药物的质谱检测方法。
为解决上述技术问题,本发明所采取的方法工艺为:(1)所述抗抑郁药样品加入亚硝酸钠溶液进行衍生反应,萃取得到衍生样品溶液;
(2)所述衍生样品溶液通过质谱全扫描,选择性离子分别为:氟西汀104.1, 117.1,177.1;去甲替林219.1,232.1,204.1;马普替林248.2,203.1,276.1,178.1;帕罗西汀358.2,138.0,109.0,329.2。
本发明所述步骤(1)中,亚硝酸钠饱和溶液加入量为25~50μL/ml抗抑郁药样品,在pH 3~4、40~60℃进行衍生反应。
本发明所述步骤(1)中,采用二氯化碳或三氯化碳进行萃取。
采用上述技术方案所产生的有益效果在于:本发明将目标物转化为极性较小的脂溶性物质进行提取检测,既有利于提取又利于气相检测,所以大大提高了检测灵敏度;与现有的衍生方法(硅烷化或酯化)比较,本发明具有副反应少的优点;本发明操作过程都近似为小型液液萃取过程,具有简单快速的特点。
附图说明
下面结合附图和具体实施方式对本发明作进一步详细的说明。
图1是本发明方法与未经衍生检测的气质色谱比较图;
图2是本发明实施例1的气质色谱图;
图3是本发明实施例2的气质色谱图;
图4是本发明实施例3的气质色谱图;
图5是本发明实施例4的气质色谱图。
具体实施方式
本仲胺类抗抑郁药物的质谱检测方法采用下述工艺:
(1)衍生反应的确立:所述仲胺类抗抑郁药物的衍生原理见公式(Ⅰ);
(Ⅰ)
由于该反应本身具有选择性,只适合仲胺分子反应,所以该衍生技术应用于实际样品选择性好。
(2)取血浆样品、尿液样品、全血样品或者其它需要检测其中仲胺类抗抑郁药物具体成分的样品溶液,在2ml样品溶液中加入饱和亚硝酸钠50~100μL,用HCl或者硝酸调节pH至3~4范围内,最好采用浓度为0.04~0.08mol/L的HCl调节;加热进行反应,反应温度40~60℃,反应时间5~10分钟;反应后进行萃取,萃取试剂为二氯化碳或三氯化碳,用量体积为2~5ml;萃取得到衍生样品溶液。
(3)检测条件:衍生样品溶液通过质谱全扫描和满足实际样品选择性要求,选择性离子分别为:氟西汀(104.1,117.1,177.1),去甲替林(219.1,232.1,204.1),马普替林(248.2,203.1,276.1,178.1),帕罗西汀(358.2,138.0,109.0,329.2)。
(4)本方法可以检测四种抗抑郁药物,各药物检测的线性范围分别为:氟西汀,0.5~80μg/L,检出下线为0.04μg/L;去甲替林0.5~80μg/L,检出下线为0.08μg/L;马普替林1.0~160μg/L,检出下线为0.20μg/L;帕罗西汀5.0~400μg/L,检出下线为1.38μg/L。
(5)准确度和灵敏度实验:在血浆和尿液中分别加入不同含量的氟西汀、去甲替林、马普替林、帕罗西汀,采用本检测方法分别进行检测,检测结果见表1。
表1:准确度和灵敏度检测结果
图1为本检测方法的气质色谱与未经衍生检测气质色谱的比较图,图中,未经衍生:a氟西汀,b去甲替林,c马普替林,d帕罗西汀;本检测方法衍生后:e氟西汀,f去甲替林,g马普替林,h帕罗西汀。本检测方法将目标物转化为极性较小的脂溶性物质进行提取检测,既有利于提取又利于气相检测,由图1可见,有效地提高了检测灵敏度。
实施例1:本仲胺类抗抑郁药物的质谱检测方法采用下述具体工艺。
量取2ml解冻后血浆样品中,加入饱和亚硝酸钠50μL,加入0.06mol/L的HCl调节pH值为3.5,充分震荡后,在60℃反应时间5分钟;用2ml二氯化碳进行萃取,15000转离心10分钟,取有机相得到衍生样品溶液。衍生样品溶液进行气相色谱-质谱质谱扫描,色谱图见图2。图中谱线为空白血浆样品和加标后血浆样品,其中a:65μg/L氟西汀;b:162.5μg/L去甲替林;c:325μg/L马普替林;d:400μg/L帕罗西汀。可见,经本方法处理后,目标物出峰出,几乎没有干扰,且灵敏度较高。
实施例2:本仲胺类抗抑郁药物的质谱检测方法采用下述具体工艺。
尿液解冻后,8000转离心10分钟, 量取2ml于10毫升玻璃离心管中,加入饱和亚硝酸钠70μL,加入0.08mol/L的HCl调节pH值为3.0,充分震荡后,在50℃反应时间10分钟;用3ml二氯化碳进行萃取,取有机相得到衍生样品溶液。衍生样品溶液进行气相色谱-质谱质谱扫描,色谱图见图3。图中谱线为空白血浆样品和加标后血浆样品,其中a:65μg/L氟西汀;b:162.5μg/L去甲替林;c:325μg/L马普替林;d:400μg/L帕罗西汀。同样,经本方法处理后,尿样中基体几乎没有干扰,且灵敏度较高。
实施例3:本仲胺类抗抑郁药物的质谱检测方法采用下述具体工艺。
量取2ml解冻后血浆样品中,加入饱和亚硝酸钠100μL,加入硝酸调节pH值为3.2,充分震荡后,在55℃反应时间8分钟;用5ml三氯化碳进行萃取,15000转离心10分钟,取有机相得到衍生样品溶液。衍生样品溶液进行气相色谱-质谱质谱扫描,色谱图见图4。图中谱线为空白血浆样品和加标后血浆样品,其中,a:20μg/L氟西汀;b:20μg/L去甲替林;c:50μg/L马普替林;d:100μg/L帕罗西汀。可见,经本方法处理后,目标物出峰出,几乎没有干扰,且灵敏度较高。
实施例4:本仲胺类抗抑郁药物的质谱检测方法采用下述具体工艺。
尿液解冻后,8000转离心10分钟, 量取2ml于10毫升玻璃离心管中,加入饱和亚硝酸钠80μL,加入0.04mol/L的HCl调节pH值为4.0,充分震荡后,在40℃反应时间7分钟;用4ml三氯化碳进行萃取,取有机相得到衍生样品溶液。衍生样品溶液进行气相色谱-质谱质谱扫描,色谱图见图5。图中谱线为空白血浆样品和加标后血浆样品,其中a:20μg/L氟西汀;b:20μg/L去甲替林;c:50μg/L马普替林;d:100μg/L帕罗西汀。同样,经本方法处理后,尿样中基体几乎没有干扰,且灵敏度较高。
Claims (3)
1.一种仲胺类抗抑郁药物的质谱检测方法,其特征在于,其方法工艺为:(1)所述抗抑郁药样品加入亚硝酸钠溶液进行衍生反应,萃取得到衍生样品溶液;
(2)所述衍生样品溶液通过质谱全扫描,选择性离子分别为:氟西汀104.1, 117.1,177.1;去甲替林219.1,232.1,204.1;马普替林248.2,203.1,276.1,178.1;帕罗西汀358.2,138.0,109.0,329.2。
2.根据权利要求1所述的仲胺类抗抑郁药物的质谱检测方法,其特征在于:所述步骤(1)中,亚硝酸钠饱和溶液加入量为25~50μL/ml抗抑郁药样品,在pH=3~4、40~60℃进行衍生反应。
3.根据权利要求1或2所述的仲胺类抗抑郁药物的质谱检测方法,其特征在于:所述步骤(1)中,采用二氯化碳或三氯化碳进行萃取。
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