中成药和保健品中非法添加化学成分的检测研究

发布时间：2018-08-27 06:05

【摘要】：目的:随着人们生活条件的改善和保健意识的提高,相对于西药毒副作用更小的中成药和保健品越来越受到人们的青睐。然而某些不法商家为了牟取暴利,在中成药和保健品中擅自添加具有一定功能的化学成分,以达到追求产品特定功效或改变产品质量特征。这些非法添加的行为给公众健康,医药发展和社会稳定都带来了巨大的危害。为了打击这些非法添加行为,国家食品药品监督管理局发布了一系列药品检验补充检验方法和检验项目批准件。然而为了规避法定检验,不法商家竟然添加标准之外的药物,这给监管部门带来了巨大的挑战。因此,建立更可靠,更有效率,检测成分覆盖面更广的检测方法对于打击非法分子和保证人民的健康安全具有巨大的现实意义。方法:本研究利用UPLC-Q-TOF/MSE采集了 121种中成药和保健品中常见非法添加的化合物的液相色谱保留时间和质谱特征碎片等信息,并利用UNIFI软件建立了该121种化合物数据库。通过利用建好的化合物数据库和设定UNIFI软件分析参数,对大量的中成药和保健品样品进行了筛查。采用UPLC-Q-TOF联用技术对止咳平喘类中成药中非法添加的9种化学成分进行定性筛查,经筛查为阳性的样品用HPLC对止咳平喘中成药中非法添加的9种化学成分进行含量检测。色谱柱采用KromasilC18(250 mm × 4.6mm,5 μm),流动相为乙腈及甲酸铵缓冲液(PH 3.65),梯度洗脱,流速为1.0 mL/min,检测波长为225 nm和280 nm针对筛查得到的磷酸可待因的阳性样品。以非法添加现象较为严重的壮阳类保健品为对象,分别运用三重四级杆串联质谱和四极杆飞行时间串联质谱对常见的壮阳类非法添加的12种化学成分进行碎片离子的采集,并通过两台仪器得到的共同碎片建立具有一定通用性的质谱数据库。同时利用碎片离子和化合物化学结构的关系,对结构类似物的典型片段进行总结和结构裂解推导。此外,依托质谱库的数据信息,建立了对壮阳类保健品快速筛查的方法。结果:本研究利用UPLC-Q-T0F/MSE结合UNIFI软件建立了 121种常见的中成药和保健品中常见非法添加化合物数据库。利用建立的数据库和UNIFI软件筛查出42批阳性样品,经与国家局发布的检验方法对其进行验证发现结果一致。本研究利用UPLC-Q-T0F技术在极短的时间内(3 min左右)实现对9种常见的止咳平喘中成药中非法添加化学成分进行分离,并且获得9种化合物的液相保留时间和特征碎片离子等信息。经筛查得到的1批样品非法添加了磷酸可待因,通过HPLC法的测定得到其含量为0.84 mg/mL。本研究建立了 12种壮阳类中成药和保健品常见的非法的化合物的具有一定通用性的质谱数据库。此外,本研究建立了对壮阳类样品快速筛查的方法。运用该快速筛查的方法,在极短的时间内(约0.1 min)便可以获取样品的质谱信息。结论:本研究利用UPLC-Q-T0F/MSE技术结合UNIFI软件建立了中成药和保健品中常见非法添加的121种化合物数据库。利用建立的数据库和UNIFI软件可实现色谱峰提取和分子式确定的自动化,大大提高了样品分析检验的效率和准确率。本研究建立的止咳平喘类中成药和保健品中9种非法添加化学成分的定性定量检验方法。增加国家食品药品监督管理总局(CFDA)补充检验方法的检测种类和缩短了分析检验时间。本研究建立的具有一定通用性的壮阳类化合物的质谱数据库,可以通过质谱库中包含同类物质典型碎片离子对质谱库中的化合物或者结构类似物进行快速筛查。检测人员在无对照品的情况下,依然能借助数据库的信息对样品进行初步筛查。
[Abstract]:OBJECTIVE: With the improvement of people's living conditions and health care awareness, Chinese patent medicines and health care products with less toxic and side effects than Western medicines are becoming more and more popular. To combat these illegal additions, the State Food and Drug Administration (SFDA) has issued a series of supplementary testing methods and approval documents for testing items. However, in order to circumvent legal inspection Therefore, it is of great practical significance to establish a more reliable, efficient and wide-ranging detection method for combating illegal elements and ensuring the health and safety of the people. The retention time and mass spectrometric fragments of 121 compounds illegally added in Chinese patent medicines and health care products were analyzed. The database of 121 compounds was established by UNIFI software. A large number of samples of Chinese patent medicines and health care products were screened by using the database and UNIFI software. UPLC-Q-TOF was used to determine the nine chemical constituents illegally added in Chinese patent medicine for cough and asthma relief. Ammonium phosphate buffer (PH 3.65), gradient elution, flow rate of 1.0 mL/min, detection wavelength of 225 nm and 280 nm were used to screen positive samples of codeine phosphate. Twelve chemicals were added illegally to collect fragment ions, and a general mass spectrometry database was established by the common fragments obtained by two instruments. The typical fragments of structural analogues were summarized and deduced by the relationship between fragment ions and chemical structure of compounds. Results: A database of 121 kinds of commonly used Chinese patent medicines and health products was established by UPLC-Q-T0F/MSE and UNIFI software. 42 batches of positive samples were screened by the database and UNIFI software, and the results were checked by the National Bureau. In this study, UPLC-Q-T0F technique was used to separate the illegally added chemical constituents of nine common Chinese patent medicines for cough and asthma in a very short time (about 3 minutes), and the retention time and characteristic fragment ions of nine compounds were obtained. Codeine phosphate was illegally added and its content was determined to be 0.84 mg/mL by HPLC. A general mass spectrometry database was established for 12 kinds of common illegal compounds in Chinese patent medicine and health care products. In addition, a rapid screening method was established for the samples of Chinese patent medicine and health care products. CONCLUSION: A database of 121 compounds commonly added illegally in Chinese patent medicines and health care products was established by UPLC-Q-T0F/MSE and UNIFI software. The database and UNIFI software can be used to extract chromatographic peaks and determine the molecular formula. This study established a qualitative and quantitative method for the determination of nine illegally added chemical components in Chinese patent medicines for cough and asthma relief and health care products. A universal mass spectrometric database for the detection of the compounds or structural analogues in the mass spectrometry library can be established by including the typical fragments of the same substances in the database.
【学位授予单位】：广州中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O657;TS218;R286.0

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