CN112525641A - 一种毛发中精神类药物待测液的制备方法 - Google Patents
一种毛发中精神类药物待测液的制备方法 Download PDFInfo
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Abstract
本发明涉及免疫诊断技术领域,针对现有技术毛发中精神类药物待测液裂解周期长的问题,公开了一种毛发中精神类药物待测液的制备方法,包括如下步骤:(1)毛发清洗:功能性蛋白基表面活性剂和纯水交替清洗毛发;(2)毛发软化:将清洗好的毛发加入软化液中浸泡软化处理,得到软化产物;(3)毛发裂解:在步骤(2)软化产物中加入裂解粉末,同时加入助磨剂,研磨裂解得到裂解产物;(4)药物小分子保存:在步骤(3)的裂解产物中加入保存液对裂解产物中的药物小分子进行稳定保存,得到待测液。本发明裂解液除了使角蛋白变性还破坏黑色素结构,裂解毛发更高效,保存液延长检测时间,有较好的重复性,使得检测结果科学严谨。
Description
技术领域
本发明涉及免疫分析检测技术领域,尤其涉及一种毛发中精神类药物待测液的制备方法。
背景技术
药物滥用严重危害社会安全和人类生命健康,随着滥用人员数量上升和年轻化,成为了社会一大热点议题,同时推动了体外诊断试剂的发展。目前,药物滥用的检测样本以尿液、唾液、血液为主。尿液检测易取样但也易掺假;唾液检测易受食物的影响,漱口等会造成药物浓度骤降;通常药物滥用48h后,尿液和唾液中药物基本代谢完全,样本提供的有效信息很少,两种检测均有漏检的可能;血液检测虽然可以提供相对可靠的检测数据,但具有侵略性,对操作人员要求高,受采样地点、保存环境等限制。
人类的毛发属于皮肤的附属器官,分为长毛(头发、胡须、腋毛、阴毛)、短毛(睫毛、眉毛、鼻毛、外耳道短毛)、毳毛和胎毛四种。人体不同部位的毛发生长速度存在差异,如头发、腋毛、胡须、臂毛、腿毛的生长速度分别为0.7-1.5cm/月、0.87-1.00cm/月、0.75-0.87cm/月、1.05cm/月、0.81-1.05cm/月,如此1cm头发段大致反映近1个月的用药情况;根据检测需求可自由选择不同部位的毛发。毛发作为检材具有易获取、易保存、易携带等优点,在药物毒品检测、法医诊断等领域具有广泛的应用前景。
毛发的主要成分为黑色素、角蛋白和脂质,摄入的药物被包埋在角蛋白中,首先需要裂解毛发释放药物分子进入溶液。常用的裂解方法包括酸水解、碱水解、酶水解、甲醇等有机溶剂裂解;酸碱水解成本较低,但裂解效率低、溶液中杂质多影响检测;有机溶液裂解操作复杂、易造成环境污染。其次对裂解液中待测物的检测方法包括气质联用色谱(GC/MS)、高效液相色谱-质谱联用(HPLC/MS)、高效毛细管电泳检测、酶联免疫法(ELISA)等,存在操作复杂、检测时间长、成本高、基层推广难等缺点。鉴于此,本发明旨在建立一种快速的、可靠的、具有追溯性的、检测时限较长的检测方法。此外,为便于检测,本发明设计了一款便携的毛发检测箱,所有操作均在检测箱内进行,收集、裂解提取、检测、留样等功能区互不干扰。所制备的待检测液直接影响到检测结果的准确度及有效性,且现有检测技术中待测液的制备周期长,且毛发中的药物提取不充分,检测效率较低。因此,迫切需要研发一种更简便、更快速及有效的毛发中精神类药物待测液的制备方法。
专利号CN201710302227.5,专利名称“毛发中大麻类化合物的提取和检测方法”,本发明涉及一种毛发中大麻类化合物的提取和检测方法。提取方法包括以下步骤:(1)将毛发清洗后,用液氮研磨,得毛发粉末;(2)取研磨后的毛发粉末加入氢氧化钠溶液,进行超声处理,离心,取上清液加入磷酸缓冲液进行缓冲,得毛发处理液;(3)将毛发处理液注入经平衡后的固相萃取柱,依次用乙酸水溶液、甲醇水溶液洗涤杂质,再用正己烷-乙酸溶液进行洗脱,收集洗脱液,即得。将收集的洗脱液用LC-MS/MS的方法进行检测,即可有效检测出毛发中含量甚微的四氢大麻酚及其代谢物的含量。
其不足之处在于,其处理步骤繁琐,裂解时间较长。
发明内容
针对现有技术毛发中精神类药物待测液裂解周期长的问题,本发明提供了一种毛发中精神类药物待测液的制备方法,本发明裂解液除了使角蛋白变性还破坏黑色素结构,裂解毛发更高效,保存液延长检测时间,有较好的重复性,使得检测结果科学严谨,极大缩短待测液的制备周期,简化制备步骤,提升毛发中精神类药物的检测效率。
为了实现上述目的,本发明采用以下技术方案:
一种毛发中精神类药物待测液的制备方法,包括如下步骤:
(1)毛发清洗:功能性蛋白基表面活性剂和纯水交替清洗毛发;
(2)毛发软化:将清洗好的毛发加入软化液中浸泡软化处理,得到软化产物;
(3)毛发裂解:在步骤(2)软化产物中加入裂解粉末,同时加入助磨剂,研磨裂解得到裂解产物;
(4)药物小分子保存:在步骤(3)的裂解产物中加入保存液对裂解产物中的药物小分子进行稳定保存,得到待测液。
本发明通过改变角蛋白和黑色素的结构达到充分释放药物分子的效果;本发明提供的毛发裂解提取不同于传统酸水解、碱水解、酶水解、有机溶剂裂解,仅仅使用简单易得的化学品,同时传统的裂解液通过改变角蛋白的结构来释放药物分子,而本裂解液除了使角蛋白变性还破坏黑色素结构,裂解毛发更高效;本裂解液适用于毛发中小分子物质的释放提取,尤其是易与黑色素结合的碱性物质和中性物质,极大缩短毛发裂解的时间;毛发通过预处理排除外界污染物的干扰,检测结果科学严谨;裂解溶液配制简单、成本低廉、药物回收率高、可操作性强;强还原剂配合高通量组织粉碎研磨仪加速药物小分子释放速度、提高释放效率、缩短释放时间;加入保存液延长检测时间、有较好的重复性。
作为优选,步骤(1)中,所述功能性蛋白基表面活性剂为含氟的醇醚磷酸单酯类化合物。
毛发清洗是为了去除可能因外界环境造成的污染,与现有技术处理方案中的有机溶剂、超声波震荡相比,本发明功能性蛋白基表面活性剂较温和,在有效去除毛发表面污染物的同时不会影响毛发内部结构。
作为优选,步骤(2)中,软化液配方为:Tris-HCl 0.05-0.1M、Na2SO4 4-10g/L、胆酸钠0.5-1.5g/L、Tween-20 0.05-0.15%、尿素2.5-5g/L、其余为纯水。
作为优选,步骤(2)中,毛发与软化液的比例为100mg:1-1.4ml。
作为优选,步骤(2)中,软化处理时间为5-10min。
软化液中Tris-HCl缓冲体系为基础;Na2SO4可明显地增大药物的回收率;胆酸钠作为Na2SO4作用的补充,也可作为蛋白去污剂,对毛发起到一定的裂解作用;吐温20作用温和、响其他化学品发挥作用,吐温20的乳化作用促进药物小分子更易进入裂解溶液中;尿素充当强变性剂,通过离子间的相互作用,打断角蛋白、黑色素分子内和分子间的各种化学键,包括氢键、共价键、范德华力等,使得药物小分子充分释放;此软化步骤可以软化毛发、增大药物回收率(即Na2SO4可明显地减轻有颜色毛发的放射性,说明Na2SO4可增大药物的回收率),同时能够促进下一步的毛发裂解。
作为优选,步骤(3)中,裂解粉末配方为SDS3.5-6.5g/L、DTT 1.25-5g/L、含巯基化合物0.15-1.0g/L、TCEP-HCl 5-10g/L。
作为优选,步骤(3)中,软化产物与裂解粉末的比例1ml:10-15mg。
作为优选,步骤(3)中,研磨裂解的时间为4-5min,所述助磨剂为陶瓷珠。
此步骤边研磨边裂解,放大裂解效果;SDS为去垢剂,可以破坏蛋白内的疏水键;DTT、含巯基化合物、TCEP-HCl为强还原剂,主要断裂毛发角质中的二硫键;强还原剂配合高通量组织粉碎研磨仪增大裂解粉末与毛发的接触面积使裂解更充分、加速药物小分子释放速度、提高释放效率、缩短释放时间。与玻璃珠、钢珠等相比,陶瓷珠成分简单、对实验结果的影响小;陶瓷珠的比重、硬度、抗压强度适中,并且3mm的陶瓷珠适用各种动植物组织。
作为优选,步骤(4)中,裂解产物与保存液的比例1ml:2μl-5μl。
作为优选,步骤(4)中,保存液的配方为H2O2 0.015-0.05ml/l、乙醇胺1-1.2mol/L、NaN3 0.02-0.04%。
H2O2为二硫键氧化剂,可在新的位置形成二硫键,保证药物分子存在于裂解液中;乙醇胺溶液,避免待检测药物分解;NaN3为防腐剂,延长溶液保存期限,因此,也极大延长了待测液的检测周期与检测结果的准确度,使得检测结果更加优化及所检测出的成分更加精准。
因此,本发明具有如下有益效果:
(1)本发明提供了一种毛发中精神类药物待测液的制备方法,本发明裂解液除了使角蛋白变性还破坏黑色素结构,裂解毛发更高效,裂解时间显著缩短;
(2)结合毛发清洗、毛发软化等步骤来实现毛发的快速裂解及减少待测液中的杂质成分,待测液制备效率较高及质量优化;
(3)保存液延长检测时间,有较好的重复性,使得检测结果科学严谨,极大缩短待测液的制备周期,简化制备步骤,提升毛发中精神类药物的检测效率。
具体实施方式
下面结合具体实施方式对本发明做进一步的描述。
总实施例
一种毛发中精神类药物待测液的制备方法,包括如下步骤:
(1)毛发清洗:功能性蛋白基表面活性剂含氟的醇醚磷酸单酯类化合物和纯水交替清洗毛发2-4次;
(2)毛发软化:将清洗好的毛发加入软化液中浸泡软化处理5-10min,得到软化产物;毛发与软化液的比例为100mg:1-1.4ml;所述软化液配方为:Tris-HCl 0.05-0.1M、Na2SO4 4-10g/L、胆酸钠0.5-1.5g/L、Tween-20 0.05-0.15%、尿素2.5-5g/L、其余为纯水。
(3)毛发裂解:在步骤(2)软化产物中加入裂解粉末,同时加入助磨剂,研磨裂解4-5min得到裂解产物;裂解粉末配方为SDS 3.5-6.5g/L、DTT 1.25-5g/L、含巯基化合物0.15-1.0g/L、TCEP-HCl 5-10g/L;
(4)药物小分子保存:在步骤(3)的裂解产物中加入保存液对裂解产物中的药物小分子进行稳定保存,得到待测液;裂解产物与保存液的比例1ml:2μl-5μl;保存液的配方为H2O20.015-0.05ml/l、乙醇胺1-1.2mol/L、NaN3 0.02-0.04%。
(5)毛发样本的检测:将毛发样本待测液加入免疫层析试纸条上,加样同时开始计时,观察质控线与检测线是否清晰、有无拖尾,5min结束计时并对结果进行分析。
实施例1
一种毛发中精神类药物待测液的制备方法,包括如下步骤:
(1)毛发清洗:功能性蛋白基表面活性剂含氟的醇醚磷酸单酯类化合物和纯水交替清洗毛发3次;
(2)毛发软化:将清洗好的毛发加入软化液中浸泡软化处理8min,得到软化产物;毛发与软化液的比例为100mg:1.2ml;所述软化液配方为:Tris-HCl 0.08M、Na2SO4 7g/L、胆酸钠1.0g/L、Tween-20 0.1%、尿素3.8g/L、其余为纯水。
(3)毛发裂解:在步骤(2)软化产物中加入裂解粉末,同时加入助磨剂,研磨裂解4.5min得到裂解产物;裂解粉末配方为SDS 5g/L、DTT 3g/L、含巯基化合物0.12g/L、TCEP-HCl 8g/L;
(4)药物小分子保存:在步骤(3)的裂解产物中加入保存液对裂解产物中的药物小分子进行稳定保存,得到待测液;裂解产物与保存液的比例1ml:4μl;保存液的配方为H2O20.038ml/l、乙醇胺1.1mol/L、NaN3 0.03%。
(5)毛发样本的检测:将毛发样本待测液加入免疫层析试纸条上,加样同时开始计时,观察质控线与检测线是否清晰、有无拖尾,5min结束计时并对结果进行分析。
收集30位吸烟人毛发和36位不吸烟人毛发,按照实施例1所述步骤进行检测,以GC/MS检测结果为参照。从检测结果来看:阳性符合率、阴性符合率、总样本符合率分别为96.7%、100%、98.5%。
表1 30位吸烟人毛发和36位不吸烟人毛发检测结果
实施例2
一种毛发中精神类药物待测液的制备方法,包括如下步骤:
(1)毛发清洗:功能性蛋白基表面活性剂含氟的醇醚磷酸单酯类化合物和纯水交替清洗毛发2次;
(2)毛发软化:将清洗好的毛发加入软化液中浸泡软化处理10min,得到软化产物;毛发与软化液的比例为100mg:1ml;所述软化液配方为:Tris-HCl 0.05M、Na2SO4 10g/L、胆酸钠0.5g/L、Tween-20 0.05%、尿素5g/L、其余为纯水。
(3)毛发裂解:在步骤(2)软化产物中加入裂解粉末,同时加入助磨剂,研磨裂解5min得到裂解产物;裂解粉末配方为SDS 6.5g/L、DTT 5g/L、含巯基化合物0.15g/L、TCEP-HCl 10g/L;
(4)药物小分子保存:在步骤(3)的裂解产物中加入保存液对裂解产物中的药物小分子进行稳定保存,得到待测液;裂解产物与保存液的比例1ml:2μl;保存液的配方为H2O20.015ml/l、乙醇胺1.2mol/L、NaN3 0.02%。
(5)毛发样本的检测:将毛发样本待测液加入免疫层析试纸条上,加样同时开始计时,观察质控线与检测线是否清晰、有无拖尾,5min结束计时并对结果进行分析。
收集吸食吗啡、冰毒、K粉、尼古丁人员的毛发,阳性毛发的鉴定以GC/MS为准,按照总实施例2逐步进行处理、检测,结果显示按照本发明制备的待测物均可检出,表示本发明制备方法有效。
表2吸食吗啡、冰毒、K粉、尼古丁人员的毛发检测结果
对比例1
与实施例1相同的毛发样本,根据现有文献公开的待测液制备方案,与本发明的待测液制备方案做对比试验:A1参照杨崇俊等的样本处理方法(参考文献:杨崇俊,张红丽,李强.高动能研磨-液质法快速检测毛发中毒品及其代谢物[J].分析试验室,2019,38(05):604-608.);A2参照胡小龙等配方(CN1096133230A);A3参照罗学港等的干裂解液配方(CN101508716A)。结果如下:A1、A2、A3与本发明制备的待测液相比,阳性符合率、总样本符合率下降,
表3.1方法A1制备30位吸烟人毛发和36位不吸烟人毛发检测结果
表3.2方法A2制备30位吸烟人毛发和36位不吸烟人毛发检测结果
表3.3方法A3制备30位吸烟人毛发和36位不吸烟人毛发检测结果
对比例2(与实施例1相同的毛发样本,与实施例1区别在于毛发不经过清洁)
一种毛发中精神类药物待测液的制备方法,包括如下步骤:
(1)毛发软化:将清洗好的毛发加入软化液中浸泡软化处理8min,得到软化产物;毛发与软化液的比例为100mg:1.2ml;所述软化液配方为:Tris-HCl 0.08M、Na2SO4 7g/L、胆酸钠1.0g/L、Tween-20 0.1%、尿素3.8g/L、其余为纯水。
(2)毛发裂解:在步骤(2)软化产物中加入裂解粉末,同时加入助磨剂,研磨裂解4.5min得到裂解产物;裂解粉末配方为SDS 5g/L、DTT 3g/L、含巯基化合物0.12g/L、TCEP-HCl 8g/L;
(3)药物小分子保存:在步骤(3)的裂解产物中加入保存液对裂解产物中的药物小分子进行稳定保存,得到待测液;裂解产物与保存液的比例1ml:4μl;保存液的配方为H2O20.038ml/l、乙醇胺1.1mol/L、NaN3 0.03%。
(4)毛发样本的检测:将毛发样本待测液加入免疫层析试纸条上,加样同时开始计时,观察质控线与检测线是否清晰、有无拖尾,5min结束计时并对结果进行分析。
与实施例1相同的毛发样本,与实施例1区别在于毛发不经过清洁,直接进行软化、裂解、保存、检测,结果显示:与实施例1结果相比,假阳率增加,阴性符合率和总样本符合率下降。
表4 30位吸烟人毛发和36位不吸烟人毛发未清洁检测结果
对比例3(与实施例1相同的毛发样本,与实施例1区别在于毛发不经过软化)
一种毛发中精神类药物待测液的制备方法,包括如下步骤:
(1)毛发清洗:功能性蛋白基表面活性剂含氟的醇醚磷酸单酯类化合物和纯水交替清洗毛发3次;
(2)毛发裂解:在毛发中加入裂解粉末,同时加入助磨剂,研磨裂解4.5min得到裂解产物;裂解粉末配方为SDS 5g/L、DTT 3g/L、含巯基化合物0.12g/L、TCEP-HCl 8g/L;
(3)药物小分子保存:在步骤(3)的裂解产物中加入保存液对裂解产物中的药物小分子进行稳定保存,得到待测液;裂解产物与保存液的比例1ml:4μl;保存液的配方为H2O20.038ml/l、乙醇胺1.1mol/L、NaN3 0.03%。
(4)毛发样本的检测:将毛发样本待测液加入免疫层析试纸条上,加样同时开始计时,观察质控线与检测线是否清晰、有无拖尾,5min结束计时并对结果进行分析。
与实施例1相同的毛发样本,与实施例1区别在于毛发不经过软化,将清洁好的毛发直接进行裂解、保存、检测,结果显示:与实施例1结果相比,假阳假阴率增加,阳性符合率、阴性符合率、总样本符合率降低。
表5 30位吸烟人毛发和36位不吸烟人毛发未软化检测结果
对比例4(与实施例1相同的毛发样本,与实施例1区别在于毛发待测液不添加保存液)一种毛发中精神类药物待测液的制备方法,包括如下步骤:
(1)毛发清洗:功能性蛋白基表面活性剂含氟的醇醚磷酸单酯类化合物和纯水交替清洗毛发3次;
(2)毛发软化:将清洗好的毛发加入软化液中浸泡软化处理8min,得到软化产物;毛发与软化液的比例为100mg:1.2ml;所述软化液配方为:Tris-HCl 0.08M、Na2SO4 7g/L、胆酸钠1.0g/L、Tween-20 0.1%、尿素3.8g/L、其余为纯水。
(3)毛发裂解:在步骤(2)软化产物中加入裂解粉末,同时加入助磨剂,研磨裂解4.5min得到裂解产物;裂解粉末配方为SDS 5g/L、DTT 3g/L、含巯基化合物0.12g/L、TCEP-HCl 8g/L;
(4)毛发样本的检测:将毛发样本待测液加入免疫层析试纸条上,加样同时开始计时,观察质控线与检测线是否清晰、有无拖尾,5min结束计时并对结果进行分析。
与实施例1相同的毛发样本,与实施例1区别在于毛发待测液不添加保存液,将清洗好的毛发进行软化、裂解、检测,结果显示阳性符合率、阴性符合率、总样本符合率与实施例1无差异,但待测液保存时间缩短、稳定性差。
表6 30位吸烟人毛发和36位不吸烟人毛发未加保存液软化检测结果
表7实施例1和对比例4所制备的待测液不同时刻的检测结果
由实施例1-2与对比例1-4的数据可知,只有在本发明权利要求范围内的方案,才能够在各方面均能满足上述要求,得出最优化的待测液。而对于配比的改动、原料的替换/加减,或者加料顺序的改变,均会带来相应的负面影响。
本发明中所用原料、设备,若无特别说明,均为本领域的常用原料、设备;本发明中所用方法,若无特别说明,均为本领域的常规方法。
以上所述,仅是本发明的较佳实施例,并非对本发明作任何限制,凡是根据本发明技术实质对以上实施例所作的任何简单修改、变更以及等效变换,均仍属于本发明技术方案的保护范围。
Claims (10)
1.一种毛发中精神类药物待测液的制备方法,其特征是,包括如下步骤:
(1)毛发清洗:功能性蛋白基表面活性剂和纯水交替清洗毛发;
(2)毛发软化:将清洗好的毛发加入软化液中浸泡软化处理,得到软化产物;
(3)毛发裂解:在步骤(2)软化产物中加入裂解粉末,同时加入助磨剂,研磨裂解得到裂解产物;
(4)药物小分子保存:在步骤(3)的裂解产物中加入保存液对裂解产物中的药物小分子进行稳定保存,得到待测液。
2.根据权利要求1所述一种毛发中精神类药物待测液的制备方法,其特征是,步骤(1)中,所述功能性蛋白基表面活性剂是一种含氟的醇醚磷酸单酯类化合物。
3.根据权利要求1或2所述一种毛发中精神类药物待测液的制备方法,其特征是,步骤(2)中,软化液配方为:Tris-HCl 0.05-0.1M、Na2SO4 4-10g/L、胆酸钠0.5-1.5g/L、Tween-200.05-0.15%、尿素2.5-5g/L、其余为纯水。
4.根据权利要求3所述一种毛发中精神类药物待测液的制备方法,其特征是,步骤(2)中,毛发与软化液的比例为100mg:1-1.4ml。
5.根据权利要求4所述一种毛发中精神类药物待测液的制备方法,其特征是,步骤(2)中,软化处理时间为5-10min。
6.根据权利要求1所述一种毛发中精神类药物待测液的制备方法,其特征是,步骤(3)中,裂解粉末配方为SDS3.5-6.5g/L、DTT 1.25-5g/L、含巯基化合物0.15-1.0g/L、TCEP-HCl5-10g/L。
7.根据权利要求1所述一种毛发中精神类药物待测液的制备方法,其特征是,步骤(3)中,软化产物与裂解粉末的比例1ml:10-15mg。
8.根据权利要求1所述一种毛发中精神类药物待测液的制备方法,其特征是,步骤(3)中,研磨裂解的时间为4-5min,所述助磨剂为陶瓷珠。
9.根据权利要求1所述一种毛发中精神类药物待测液的制备方法,其特征是,步骤(4)中,裂解产物与保存液的比例1ml:2μl-5μl。
10.根据权利要求1所述一种毛发中精神类药物待测液的制备方法,其特征是,步骤(4)中,保存液的配方为H2O2 0.015-0.05ml/l、乙醇胺1-1.2 mol/L、NaN3 0.02-0.04%。
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