基于最小二乘支持向量机的色谱指纹图谱预测银杏叶总抗氧化活性

在色谱图基线校正和色谱峰匹配基础上,提出以40个银杏叶提取物HPLC指纹图谱的色谱图轮廓作为输入,相应的提取物总抗氧化活性作为输出,建立最小二乘支持向量机回归模型,并对包含10个样本的测试集进行了预测.最小二乘支持向量机的测试集预测误差均方根(RMSEP)为0.0230,预测结果优于目前普遍使用的误差反向传播神经网络和偏最小二乘回归.与采用色谱峰面积为分析变量的模型预测结果比较表明:采用消除干扰后的色谱图全谱轮廓保留了样本的全部信息,预测结果更好     

中药材提取物的混批勾兑研究

采用非线性最小二乘拟合计算中药材提取物的勾兑系数,不同批的中药材提取物经过勾兑后与参照样品的差异减小,各成分含量稳定。采用数据预处理的方法,并对数据预处理方法进行改进,使峰面积较小的色谱峰可以实现较小的相对差异。引入误差控制系数,可实现对特定色谱峰的控制要求。实验结果表明,非线性最小二乘拟合可以用于计算中药材提取物的勾兑系数。     

CO2超临界提取和水蒸汽蒸馏提取桂皮中化学成分的分析

采用气相色谱-质谱联用技术对桂皮的CO2超临界提取物和水蒸汽蒸馏提取物进行了分析.分别分离出了36个峰和32个峰,用峰面积归一化法定量测定了组分的相对含量并进行了对比,其CO2超临界提取物较水蒸汽蒸馏法提取物多4个峰,其含量也有一定的差别.比较了两种提取方法的差异.     

基于Jaccard系数提高核磁共振波谱代谢物数据库匹配的精度

NMR代谢组学检测完成后,人们通常基于化学位移值在人类代谢组学数据库(human metabolome database,HMDB)上进行手动代谢物匹配,然而该方法对代谢物的鉴定较为粗糙,准确度不高。本研究试图基于建立一种更加合理,且能够自动寻峰并根据数据库匹配代谢物方法。通过分析HMDB的峰匹配方法,提出了基于Jaccard系数和匹配率(匹配的峰数目/总峰数)的新方法,基于MATLAB编程实现,然后比较HMDB中1D NMR search和本方法对于同一段随机化学位移列表的匹配结果。分析结果显示,对于同一随机化学位移列表,HMDB的匹配结果中排在前20位的物质峰数目超过16的占60%,说明其匹配方法偏向于峰数目较多的物质;HMDB用于峰匹配排序的评分与峰匹配率有明显区别,而本方法匹配评分与匹配率较为接近;且HMDB匹配结果排在第10位的物质与该随机序列没有可匹配的化学位移值。本文对于HMDB峰匹配算法存在的不足进行了改进,并发现基于Jaccard分数的匹配算法能够提高根据代谢物数据库进行NMR代谢物鉴定的精度。     

多波长自动融合指纹图谱策略及其在蜂胶质量评价中的应用

提出了一种简化数据处理过程的多波长自动融合指纹图谱策略,并应用于蜂胶乙醇提取物的质量评价。运用超高效液相色谱（UPLC）技术对5个厂家的15批蜂胶乙醇提取物进行220、245、270、320 nm的多波长检测。样品采用Agilent Poroshell 120 EC-C18(3 mm×100 mm,2.7μm)色谱柱进行分离;以甲醇-0.2%磷酸水溶液为流动相进行梯度洗脱。利用“中药色谱指纹图谱相似度评价系统”进行全峰匹配,实现了每个样品多个波长下各色谱峰数据的自动融合。以270 nm单波长为对照,比较其与多波长融合在共有色谱峰、相似度评价、聚类分析、主成分分析方面的差异。蜂胶多波长融合指纹图谱包含33个特征峰,其中14个特征峰可定性,分别为咖啡酸、ρ-香豆酸、阿魏酸、异阿魏酸、3,4-二甲氧基肉桂酸、肉桂酸、槲皮素、山奈素、芹菜素、异鼠李素、乔松素、白杨素、高良姜素、咖啡酸苯乙酯。各批次特征峰保留时间的相对标准偏差（RSD）均小于1.00%,峰面积RSD为14.39%～112.02%,平均值为37.94%。15批蜂胶融合指纹图谱的相似度为0.902～0.994,主成分分析、聚类分析均...     

基于色谱峰形优劣的代谢组学峰检测参数优化算法比较

非靶向代谢组学数据预处理的关键步骤之一为峰检测（Peak picking）,在高分辨质谱的峰检测过程中应用最广泛的算法为基于连续小波变换的cent Wave算法。本研究通过代谢物标准品和尿液两个数据集,结合优良峰形色谱峰比例、可信色谱峰比例和可重复色谱峰比例3个评价指标对IPO(Isotopologue parametersoptimization)和cent Wave Sweep两种cent Wave参数优化算法进行了全面比较。为了快速准确地对色谱峰形优劣进行区分,比较了随机森林（Random forest）、自适应提升（Adaboost）和梯度提升树（Gradient boosting decisiontree） 3种集成学习算法在区分色谱峰形优劣方面的性能。根据准确度和衡量二分类模型精确度的F1分数,选择随机森林建立区分模型（准确度93.5%, F1分数0.938）。研究结果表明,相比于XCMS Online推荐的参数,采用IPO和cent Wave Sweep进行参数优化后,不同数据集的可信色谱峰比例和可重复色谱峰比例均得到了提高,取得了较好的优化效果;但是,对于不同数据集的优...     

一种新的基于多重液相色谱-质谱实验肽信号峰形相似性的校准算法

提出了一种基于多次重复液相色谱-质谱(LC-MS)实验,结合肽信号时间差校准的峰形相似性统计学习模型,解决了重复实验数据肽链校准匹配准确性与覆盖率低的问题。采用统计学习的方法,首先建立时间差统计模型,结果表明仅靠时间特征无法完全消除校准误差。因此,除了时间特征,引入了峰形相似性特征,即认为同一种肽链在多次重复实验谱图中会产生相似的LC峰形。通过选取训练数据集,提出了一种新的基于LC峰形相似性的肽信号校准算法,并通过测试序列完成模型测试。结果表明,改进算法的准确率达98. 3%;将该数学模型应用于校准匹配两个实验数据的所有LC-MS/MS肽链,其覆盖率达91. 0%。峰形相似性特征结合时间特征可以提升多次重复LC-MS实验中相关肽链信号的匹配校准的准确性与覆盖率。     

唐古特大黄乙醇提取物的HPLC指纹图谱研究

用高效液相色谱法建立唐古特大黄乙醇提取物的指纹图谱分析方法。采用Phenomenex Kromasil C18色谱柱(4.6 mm×250 mm,5μm);甲醇-0.1%H3PO4为流动相,梯度洗脱,检测波长为270 nm,以大黄酸为参照峰。结果共有18个共有峰。此法为有效地控制唐古特大黄乙醇提取物的质量提供了依据。     

中药指纹图谱共有峰的自动识别

依托时间匹配、光谱信息辅助,利用自编的VB程序,建立并比较了时间匹配和时间匹配参考光谱信息两种识别中药指纹图谱共有峰的方法,并成功地应用于肉苁蓉的高效液相色谱-二极管阵列检测器(HPLC-DAD)法指纹图谱的建立.结果表明,只需要人为设置色谱峰大小下限、保留值相对误差上限和最大吸收波长差值上限三个参数,VB程序编制的指纹分析系统就能快速对所有样本进行共有峰识别和模糊数学处理,实现了无人工干预下的中药指纹图谱共有峰的自动识别,指纹图谱的建立过程客观,并且节省大量时间,其中参考光谱法识别结果更准确.     

银杏叶提取物的多维指纹图谱研究

利用高效液相色谱/二极管阵列检测/质谱/质谱法,建立了银杏叶提取物的多维指纹图谱,同时建立了总离子流指纹图谱,使同时检测银杏叶中两类有效成分黄酮和内酯类化合物成为可能。采用Zorbax SB-C18色谱柱(250 mm×4.6 mm i.d., 5 μm),流动相为水(含0.5 %甲酸)和乙腈,二元梯度洗脱,流速为1.0 mL/min,350 nm下检测。采用电喷雾离子源,负离子检测模式下采集质谱数据。利用指纹图谱相似度计算软件,以芦丁为内参比峰,考察了不同厂家银杏叶提取物与标准银杏叶提取物EGb 761     

Scalable distance similarity of chemical structures

Screening a library of molecular graphs for an exact or approximate match with one particular molecular graph, the query graph, is reduced to list comparisons. The lists contain lengths of shortest paths in graph Voronoi regions. This induces the notion of shortest path similarity. All graphs that are shortest path similar to the query graph are efficiently retrievable. The same applies to approximate or similarity matching. For the retrieval of all superstructures of a query, shortest path lists are modified to distance patterns. This also allows algorithmic support for query construction.     

Bayesian peak tracking: A novel probabilistic approach to match GCxGC chromatograms

A novel peak tracking method based on Bayesian statistics is proposed. The method consists of assigning (i.e. tracking) peaks from two GCxGC-FID data sets of the same sample taken in different conditions. Opposed to traditional (i.e. deterministic) peak tracking algorithms, in which the assignment problem is solved with a unique solution, the proposed algorithm is probabilistic. In other words, we quantify the uncertainty of matching two peaks without excluding other possible candidates, ranking the possible peak assignments regarding their posterior probability. This represents a significant advantage over existing deterministic methods. Two algorithms are presented: the blind peak tracking algorithm (BPTA) and peak table matching algorithm (PTMA). PTMA method was able to assign correctly 78% of a selection of peaks in a GCxGC-FID chromatogram of a diesel sample and proved to be extremely fast.     

MASSIS: a mass spectrum simulation system. 2: Procedures and performance

The use of the mass spectral simulation system, MASSIS, is reported and its performance has been evaluated. The search for substructures matching with fragments stored in four pivot databases was realised using the Ullmann algorithm. Special cleavage rules, such as the McLafferty rearrangement, the retro-Diels-Alder reaction, elimination of a neutral small molecule and oxygen migration, are processed through shortest path and depth-first search algorithms. For a search in the database of small fragments, the key step is to determine the tautomeric fragments; then a match can be obtained using a subgraph isomorphism algorithm. A string match is used to determine peak intensity. If the limited environment of an atom is the same as that found in the database of relationships between fragment and intensity, this intensity value is assigned to the query atom. Performance in a set of tests is very important in evaluating the system performance. A comparison of peaks with an intensity greater than 5% (relative) shows that our system has a very high performance figure (> 90% ) for routine organic compounds.     

Unravelling the composition of very complex samples by comprehensive gas chromatography coupled to time-of-flight mass spectrometry. Cigarette smoke

The potential and current limitations of comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC x GC-TOF-MS) for the analysis of very complex samples were studied with the separation of cigarette smoke as an example. Because of the large number of peaks in such a GC x GC chromatogram it was not possible to perform manual data processing. Instead, the GC-TOF-MS software was used to perform peak finding, deconvolution and library search in an automated fashion; this resulted in a peak table containing some 30000 peaks. Mass spectral match factors were used to evaluate the library search results. The additional use of retention indices and information from second-dimension retention times can substantially improve the identification. The combined separation power of the GC x GC-TOF-MS system and the deconvolution algorithm provide a system with a most impressive separation power.     

Simultaneous LC Determination of Chlorogenic Acid and Hydrochlorthiazide in Zhenju Jiangya Tablets

A method has been developed to determine chlorogenic acid and hydrochlorothiazide simultaneously in Zhenju Jiangya tablets by HPLC using an isocratic mode and UV detection. A solution of acetonitrile-0.4% phosphoric acid (13:87, v/v) was used as mobile phase. Results showed that the two compounds were well separated. Chlorogenic acid and hydrochlorothiazide had good linearities in the range of 0.64～6.4 μg mL^?1 and 0.08～0.16 mg mL^?1, respectively with average recoveries of 96.5～99.3 and 97.7～101.0%.     

Finding pathways between distant local minima

We report a new algorithm for constructing pathways between local minima that involve a large number of intervening transition states on the potential energy surface. A significant improvement in efficiency has been achieved by changing the strategy for choosing successive pairs of local minima that serve as endpoints for the next search. We employ Dijkstra's algorithm [E. W. Dijkstra, Numer. Math. 1, 269 (1959)] to identify the "shortest" path corresponding to missing connections within an evolving database of local minima and the transition states that connect them. The metric employed to determine the shortest missing connection is a function of the minimized Euclidean distance. We present applications to the formation of buckminsterfullerene and to the folding of various biomolecules: the B1 domain of protein G, tryptophan zippers, and the villin headpiece subdomain. The corresponding pathways contain up to 163 transition states and will be used in future discrete path sampling calculations.     

色谱指纹图谱在香精香料质量控制中的应用

烟用香精香料化学成分复杂,现无合适的化学质量控制方法,通过实例,对10个批次正常生产的香料标样进行同时蒸馏萃取,取其萃取液进行气相色谱氢焰检测.进行同组分色谱峰的匹配,根据相对峰面积求出标准指纹图谱,然后10批标样各自与标准指纹图谱进行相似度计算,据此设立待测样品的合格性允差范围.待测样品与标准指纹图谱进行谱峰匹配,计算与标准指纹图谱的相似度,依据合格性允差范围,判定其质量状况.     

Generalized Gaussian reference curve measurement model for high‐performance liquid chromatography with diode array detector separation and its solution by multi‐target intermittent particle swarm optimization

In order to separate a high‐performance liquid chromatography with diode array detector (HPLC‐DAD) data set to chromatogram peaks and spectra for all compounds, a separation method based on the model of generalized Gaussian reference curve measurement (GGRCM) and the algorithm of multi‐target intermittent particle swarm optimization (MIPSO) is proposed in this paper. A parameter θ is constructed to generate a reference curve r(θ) for a chromatogram peak based on its physical principle. The GGRCM model is proposed to calculate the fitness ε(θ) for every θ, which indicates the possibility for the HPLC‐DAD data set to contain a chromatogram peak similar to the r(θ). The smaller the fitness is, the higher the possibility. The algorithm of MIPSO is then introduced to calculate the optimal parameters by minimizing the fitness mentioned earlier. Finally, chromatogram peaks are constructed based on these optimal parameters, and the spectra are calculated by an estimator. Through the simulations and experiments, the following conclusions are drawn: (i) the GGRCM‐MIPSO method can extract chromatogram peaks from simulation data set without knowing the number of the compounds in advance even when a severe overlap and white noise exist and (ii) the GGRCM‐MIPSO method can be applied to the real HPLC‐DAD data set. Copyright © 2014 John Wiley & Sons, Ltd.     

Utilizing a constant peak width transform for isothermal gas chromatography

A computational approach to partially address the general elution problem (GEP), and better visualize, isothermal gas chromatograms is reported. The theoretical computational approach is developed and applied experimentally. We report a high speed temporally increasing boxcar summation (TIBS) transform that, when applied to the raw isothermal GC data, converts the chromatographic data from the initial time domain (in which the peak widths in isothermal GC increase as a function of their retention factors, k), to a data point based domain in which all peaks have the same peak width in terms of number of points in the final data vector, which aides in preprocessing and data analysis, while minimizing data storage size. By applying the TIBS transform, the resulting GC chromatogram (initially collected isothermally), appears with an x-axis point scale as if it were instrumentally collected using a suitable temperature program. A high speed GC isothermal separation with a test mixture containing 10 compounds had a run time of ～25 s. The peak at a retention factor k ～0.7 had a peak width of ～55 ms, while the last eluting peak at k ～89 (i.e., retention time of ～22 s) had a peak width of ～2000 ms. Application of the TIBS transform increased the peak height of the last eluting peak 45-fold, and S/N ～20-fold. All peaks in the transformed test mixture chromatogram had the width of an unretained peak, in terms of number of data points. A simulated chromatogram at unit resolution, studied using the TIBS transform, provided additional insight into the benefits of the algorithm.     

Influence of the peak height distribution on separation performances: Discrimination factor and effective peak capacity

Summary A new index of performance of the chromatographic separation between two adjacent peaks, the discrimination factor, d₀, is defined. It is normalized between 0 and 1 and is directly and easily determined from the chromatogram. It does not depend on any assumption regarding peak shape, except that the peak profiles of individual sample components have a single mode. Its value depends on the relative heights of the two peaks as well as on their separation. The separation power of a chromatographic system is classically measured by its peak capacity, defined on the basis of constant resolution between adjacent peaks. A previously developed statistical theory of the composition of mixtures makes it possible to extend the concept of peak capacity by taking into account the peak height distribution in typical average chromatograms. A new parameter, the effective peak capacity, is defined for this purpose on the basis of a constant discrimination factor between adjacent peaks. It allows to take into account the distribution of peak heights in statistical theories of the evaluation of complex chromatograms and in the measurement of the limit of determination in quantitative analysis. The characteristics of the two new parameters, the discrimination factor and effective peak capacity, are discussed and compared with those of their classical homologs, resolution and peak capacity, in the case of gaussian component peaks of equal widths.