【摘要】：目的:隨著人們生活條件的改善和保健意識(shí)的提高,相對(duì)于西藥毒副作用更小的中成藥和保健品越來越受到人們的青睞。然而某些不法商家為了牟取暴利,在中成藥和保健品中擅自添加具有一定功能的化學(xué)成分,以達(dá)到追求產(chǎn)品特定功效或改變產(chǎn)品質(zhì)量特征。這些非法添加的行為給公眾健康,醫(yī)藥發(fā)展和社會(huì)穩(wěn)定都帶來了巨大的危害。為了打擊這些非法添加行為,國家食品藥品監(jiān)督管理局發(fā)布了一系列藥品檢驗(yàn)補(bǔ)充檢驗(yàn)方法和檢驗(yàn)項(xiàng)目批準(zhǔn)件。然而為了規(guī)避法定檢驗(yàn),不法商家竟然添加標(biāo)準(zhǔn)之外的藥物,這給監(jiān)管部門帶來了巨大的挑戰(zhàn)。因此,建立更可靠,更有效率,檢測(cè)成分覆蓋面更廣的檢測(cè)方法對(duì)于打擊非法分子和保證人民的健康安全具有巨大的現(xiàn)實(shí)意義。方法:本研究利用UPLC-Q-TOF/MSE采集了 121種中成藥和保健品中常見非法添加的化合物的液相色譜保留時(shí)間和質(zhì)譜特征碎片等信息,并利用UNIFI軟件建立了該121種化合物數(shù)據(jù)庫。通過利用建好的化合物數(shù)據(jù)庫和設(shè)定UNIFI軟件分析參數(shù),對(duì)大量的中成藥和保健品樣品進(jìn)行了篩查。采用UPLC-Q-TOF聯(lián)用技術(shù)對(duì)止咳平喘類中成藥中非法添加的9種化學(xué)成分進(jìn)行定性篩查,經(jīng)篩查為陽性的樣品用HPLC對(duì)止咳平喘中成藥中非法添加的9種化學(xué)成分進(jìn)行含量檢測(cè)。色譜柱采用KromasilC18(250 mm × 4.6mm,5 μm),流動(dòng)相為乙腈及甲酸銨緩沖液(PH 3.65),梯度洗脫,流速為1.0 mL/min,檢測(cè)波長為225 nm和280 nm針對(duì)篩查得到的磷酸可待因的陽性樣品。以非法添加現(xiàn)象較為嚴(yán)重的壯陽類保健品為對(duì)象,分別運(yùn)用三重四級(jí)桿串聯(lián)質(zhì)譜和四極桿飛行時(shí)間串聯(lián)質(zhì)譜對(duì)常見的壯陽類非法添加的12種化學(xué)成分進(jìn)行碎片離子的采集,并通過兩臺(tái)儀器得到的共同碎片建立具有一定通用性的質(zhì)譜數(shù)據(jù)庫。同時(shí)利用碎片離子和化合物化學(xué)結(jié)構(gòu)的關(guān)系,對(duì)結(jié)構(gòu)類似物的典型片段進(jìn)行總結(jié)和結(jié)構(gòu)裂解推導(dǎo)。此外,依托質(zhì)譜庫的數(shù)據(jù)信息,建立了對(duì)壯陽類保健品快速篩查的方法。結(jié)果:本研究利用UPLC-Q-T0F/MSE結(jié)合UNIFI軟件建立了 121種常見的中成藥和保健品中常見非法添加化合物數(shù)據(jù)庫。利用建立的數(shù)據(jù)庫和UNIFI軟件篩查出42批陽性樣品,經(jīng)與國家局發(fā)布的檢驗(yàn)方法對(duì)其進(jìn)行驗(yàn)證發(fā)現(xiàn)結(jié)果一致。本研究利用UPLC-Q-T0F技術(shù)在極短的時(shí)間內(nèi)(3 min左右)實(shí)現(xiàn)對(duì)9種常見的止咳平喘中成藥中非法添加化學(xué)成分進(jìn)行分離,并且獲得9種化合物的液相保留時(shí)間和特征碎片離子等信息。經(jīng)篩查得到的1批樣品非法添加了磷酸可待因,通過HPLC法的測(cè)定得到其含量為0.84 mg/mL。本研究建立了 12種壯陽類中成藥和保健品常見的非法的化合物的具有一定通用性的質(zhì)譜數(shù)據(jù)庫。此外,本研究建立了對(duì)壯陽類樣品快速篩查的方法。運(yùn)用該快速篩查的方法,在極短的時(shí)間內(nèi)(約0.1 min)便可以獲取樣品的質(zhì)譜信息。結(jié)論:本研究利用UPLC-Q-T0F/MSE技術(shù)結(jié)合UNIFI軟件建立了中成藥和保健品中常見非法添加的121種化合物數(shù)據(jù)庫。利用建立的數(shù)據(jù)庫和UNIFI軟件可實(shí)現(xiàn)色譜峰提取和分子式確定的自動(dòng)化,大大提高了樣品分析檢驗(yàn)的效率和準(zhǔn)確率。本研究建立的止咳平喘類中成藥和保健品中9種非法添加化學(xué)成分的定性定量檢驗(yàn)方法。增加國家食品藥品監(jiān)督管理總局(CFDA)補(bǔ)充檢驗(yàn)方法的檢測(cè)種類和縮短了分析檢驗(yàn)時(shí)間。本研究建立的具有一定通用性的壯陽類化合物的質(zhì)譜數(shù)據(jù)庫,可以通過質(zhì)譜庫中包含同類物質(zhì)典型碎片離子對(duì)質(zhì)譜庫中的化合物或者結(jié)構(gòu)類似物進(jìn)行快速篩查。檢測(cè)人員在無對(duì)照品的情況下,依然能借助數(shù)據(jù)庫的信息對(duì)樣品進(jìn)行初步篩查。
[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.
【學(xué)位授予單位】：廣州中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：O657;TS218;R286.0

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