高温炮制药材中丙烯酰胺含量测定及控制因素的研究
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摘要
最近研究发现,高温加热的淀粉类食品中都含有高剂量的丙烯酰胺。而丙烯酰胺是一种神经毒素,是潜在的致癌物质。建立各种高温加热食品基质中丙烯酰胺的检测方法,以及通过控制热加工方法和程序抑制加工过程中丙烯酰胺的生成,是世界各国近年来在食品安全领域的一个重要的研究课题。尽管近年来在世界各国科学家共同努力下建立了几十种适合不同加热食品中丙烯酰胺测定的新方法,并且我国食品中丙烯酰胺检验的国家标准也已经处于验收阶段。但我们发现到目前为止各种分析方法均是基于高温处理的食品基质,而没有关注药物领域中丙烯酰胺的测定。而很多中药在使用前需要高温炮制,并且这些药物很多富含淀粉,那么这些药物在高温炮制过程中是否产生丙烯酰胺呢?为了回答这个问题,本文选择了常见高温炮制的谷芽、麦芽等作为测试对象,并建立了相应的分析方法。这种研究对于我国这样一个中药使用和出口大国,无论是从探索中药的作用机理、用药安全来讲,还是从破解可能的技术壁垒,增强中药出口竞争能力来讲,都具有重要的研究价值。
液相色谱-串联质谱法(HPLC-MS-MS)是近年来发展起来的一种高效的检测技术,液相色谱-质谱联用技术结合了色谱、质谱两者的优点,将液相色谱的高分离性能和质谱的高鉴别特点相结合,组成了完美的现代分析技术,得到很大的重视和发展。目前食品中丙烯酰胺的分析主要采用气相色谱-质谱法(GC-MS)与液相色谱串联质谱法(LC-MS/MS)。本文将液相色谱-串联质谱法应用于中药中丙烯酰胺的研究,建立了中药中丙烯酰胺的液相色谱-串联质谱的检测方法。以水提取,利用Oasis HLB串联BOND ELUT LRC-PRS固相萃取柱对样品进行净化；以Atlantis C18色谱柱为分析柱,以0.05%甲酸水溶液-0.1%甲酸乙睛(体积比为98：2)为流动相,LC-MS/MS测定。方法的线性范围为5-100μg/L,线性相关系数为0.9999。方法的定性限为0.002mg/kg,定量限为0.007mg/kgo高、中、低3个浓度水平的加标回收率为94.36%-101.04%，相对标准偏差小于10%。
本文并对影响丙烯酰胺生成的各种因素进行了研究。同时在对丙烯酰胺的的研究中发现温度和炮制时间是影响丙烯酰胺生成的重要因素。希望为我国中药中丙烯酰胺的研究提供一定的理论和方法参考,控制或减少中药加工中丙烯酰胺的形成。
全文共分3章：
第1章综述了近年来丙烯酰胺的重要分析手段,以及生成丙烯酰胺诸多影响因素的研究。
第2章液相色谱-串联质谱法测定谷芽和炒谷芽中丙烯酰胺的含量。考察了不同色谱柱、不同流动相对结果测定的影响,并考察了基质效应的影响。
第3章考察了温度、炮制时间对丙烯酰胺生成的影响。发现两者均是影响丙烯酰胺生成的重要因素。
It was reported that acrylamide is a neurotoxin and a probable human carcinogen. And many heat-processed foods contained relatively high levels of acrylamide. Thus, it is of significant importance to study the ways to inhibit the production of acrylamide in these foods. Liquid Chromatography-Tandem Mass Spectrometer (LC-MS/MS) is a new highly-efficient isolation technique, which has developed very fast in the recent years. It combines the advantages of chromatogram and mass spectrum, which is high separating efficiency and high distinction characteristic, and becomes a modern analysis technique, especially, liquid chromatography in hyphenation with tandem MS have been paid attention and developed. Methods of gas chromatographic mass spectrometer (GC-MS) or liquid chromatographic mass spectrometer, with MS/MS mode, are generally used to analyze the acrylamide in foodstuffs. But the LC-MS/MS is many used in any compound analyse.
The thesis introduces the applications of HPLC-MS-MS in the research of acrylamides in Chinese traditional medicine, establishes a HPLC-MS/MS method for detection of acrylamides in Chinese traditional medicine. Extracts water and clean-up of samples were performed on an Oasis HLB and BOND ELUT LRC-PRS solid phase extraction cart ridge. With a Atlantis C18 analytical column and ACN containing 0.1% formic acid-water containing 0.05 % formic acid (2 : 98, v/v) as mobile phases. The calibration curve of acrylamide showed good linearity in the range of 5-100μg/L with correlation coefficient of 0.9999. The detection limit of the method was 0.002mg/kg (S/N= 3), and the limit of quantification was 0.007mg/kg (S/N=10). The average recoveries at three levels ranged from 94.36% to 101.04% (n= 6), and the relative standard derivations were lower than 10%.
The thesis researches the factors which affect the production of acrylamide and find out that temperature and heat-processed time is an important factor. So as to supply certain theory and method references for studying acrylamide in chinese traditional medicine, to control or reduce the acrylamide formation.There are 3chapters in all.
Chapter 1:Summarize present important analysis method for detection of acrylamide。Research of factors which affect the production of acrylamide。Research of analysis method for detection of macrolides.
Chapter 2:LC-MS/MS for determination of acrylamide content in seed-corn and baked seed-corn and investigation the effects of matrix.
Chapter 3:Investigate the effects of temperature and baked time content to the production of acrylamide. Find out temperature and baked time is all important factor.
液相色谱-串联质谱法(HPLC-MS-MS)是近年来发展起来的一种高效的检测技术,液相色谱-质谱联用技术结合了色谱、质谱两者的优点,将液相色谱的高分离性能和质谱的高鉴别特点相结合,组成了完美的现代分析技术,得到很大的重视和发展。目前食品中丙烯酰胺的分析主要采用气相色谱-质谱法(GC-MS)与液相色谱串联质谱法(LC-MS/MS)。本文将液相色谱-串联质谱法应用于中药中丙烯酰胺的研究,建立了中药中丙烯酰胺的液相色谱-串联质谱的检测方法。以水提取,利用Oasis HLB串联BOND ELUT LRC-PRS固相萃取柱对样品进行净化；以Atlantis C18色谱柱为分析柱,以0.05%甲酸水溶液-0.1%甲酸乙睛(体积比为98：2)为流动相,LC-MS/MS测定。方法的线性范围为5-100μg/L,线性相关系数为0.9999。方法的定性限为0.002mg/kg,定量限为0.007mg/kgo高、中、低3个浓度水平的加标回收率为94.36%-101.04%，相对标准偏差小于10%。
本文并对影响丙烯酰胺生成的各种因素进行了研究。同时在对丙烯酰胺的的研究中发现温度和炮制时间是影响丙烯酰胺生成的重要因素。希望为我国中药中丙烯酰胺的研究提供一定的理论和方法参考,控制或减少中药加工中丙烯酰胺的形成。
全文共分3章：
第1章综述了近年来丙烯酰胺的重要分析手段,以及生成丙烯酰胺诸多影响因素的研究。
第2章液相色谱-串联质谱法测定谷芽和炒谷芽中丙烯酰胺的含量。考察了不同色谱柱、不同流动相对结果测定的影响,并考察了基质效应的影响。
第3章考察了温度、炮制时间对丙烯酰胺生成的影响。发现两者均是影响丙烯酰胺生成的重要因素。
It was reported that acrylamide is a neurotoxin and a probable human carcinogen. And many heat-processed foods contained relatively high levels of acrylamide. Thus, it is of significant importance to study the ways to inhibit the production of acrylamide in these foods. Liquid Chromatography-Tandem Mass Spectrometer (LC-MS/MS) is a new highly-efficient isolation technique, which has developed very fast in the recent years. It combines the advantages of chromatogram and mass spectrum, which is high separating efficiency and high distinction characteristic, and becomes a modern analysis technique, especially, liquid chromatography in hyphenation with tandem MS have been paid attention and developed. Methods of gas chromatographic mass spectrometer (GC-MS) or liquid chromatographic mass spectrometer, with MS/MS mode, are generally used to analyze the acrylamide in foodstuffs. But the LC-MS/MS is many used in any compound analyse.
The thesis introduces the applications of HPLC-MS-MS in the research of acrylamides in Chinese traditional medicine, establishes a HPLC-MS/MS method for detection of acrylamides in Chinese traditional medicine. Extracts water and clean-up of samples were performed on an Oasis HLB and BOND ELUT LRC-PRS solid phase extraction cart ridge. With a Atlantis C18 analytical column and ACN containing 0.1% formic acid-water containing 0.05 % formic acid (2 : 98, v/v) as mobile phases. The calibration curve of acrylamide showed good linearity in the range of 5-100μg/L with correlation coefficient of 0.9999. The detection limit of the method was 0.002mg/kg (S/N= 3), and the limit of quantification was 0.007mg/kg (S/N=10). The average recoveries at three levels ranged from 94.36% to 101.04% (n= 6), and the relative standard derivations were lower than 10%.
The thesis researches the factors which affect the production of acrylamide and find out that temperature and heat-processed time is an important factor. So as to supply certain theory and method references for studying acrylamide in chinese traditional medicine, to control or reduce the acrylamide formation.There are 3chapters in all.
Chapter 1:Summarize present important analysis method for detection of acrylamide。Research of factors which affect the production of acrylamide。Research of analysis method for detection of macrolides.
Chapter 2:LC-MS/MS for determination of acrylamide content in seed-corn and baked seed-corn and investigation the effects of matrix.
Chapter 3:Investigate the effects of temperature and baked time content to the production of acrylamide. Find out temperature and baked time is all important factor.
引文
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