近红外光谱法结合PLS测定夏枯草中的水分

采用近红外(NIR)光谱技术结合偏最小二乘法(PLS)测定夏枯草中的水分.运用NIR漫反射光谱技术采集夏枯草的NIR光谱,以烘干法测得的水分含量为参考值,结合PLS法建立夏枯草中水分测定的NIR分析模型,并以未知样品验证.所建模型的校正集内部交叉验证相关系数(R2)、校正均方差(RMSEC)和预测均方差(RMSEP)分别为0.988 2、0.129和0.134,验证集的NIR预测值与烘干法的参考值之间的差异无统计学意义.     

基于偏最小二乘法的近红外光谱模型用于丹参口服液提取过程的分析

目的探讨丹参口服液提取过程采用近红外光谱(NIR)分析的可能性及其方法。方法制备共122份提取液,采用高效液相色谱法(HPLC)测定原儿茶醛含量,并收集NIR图,用偏最小二乘法(PLS)建立校正模型。结果采用二阶求导及Savitzky-Golay平滑处理后的校正模型交叉验证均方根误差(RMSECV)为3.456,相关系数为0.988,优于其他优化方式。结论基于PLS的原儿茶醛NIR模型可用于丹参口服液提取过程的在线分析。     

近红外光谱模型用于姜黄素-赖氨酸共晶含量分析

目的探讨近红外光谱(NIR)分析姜黄素-赖氨酸共晶含量的可行性。方法制备共60份不同含量的b型结晶,采用溶剂提取法和高效液相色谱法(HPLC)测定游离态姜黄素含量,并收集NIR图,用偏最小二乘法(PLS)建立校正模型。结果采用原始图谱及Noriss平滑处理后的校正模型交叉验证均方根误差(RMSECV)为3.456,相关系数为0.988,优于其他优化方式。结论基于PLS的NIR模型可用于药物共晶的含量分析。     

黄柏中多种生物碱测定的NIR模型的建立

目的:建立黄柏中3个成分(木兰花碱、黄柏碱、小檗碱)测定的NIR模型。方法:以高效液相测定的黄柏生物碱含量值作为参照,运用近红外漫反射光谱采集49批不同产地样品的近红外漫反射光谱,采用偏最小二乘算法(PLS)建立校正模型,比较不同的预处理方法及不同的波段对建模的影响。结果:以MSC+2D2为预处理方法,建立的小檗碱、黄柏碱、木兰花碱模型交互验证均方根误差(RMSEC)分别为0.0453、0.0335、0.0396,相关系数(R2)分别为0.9995、0.9760、0.9306。结论:建立的NIR模型稳定准确可靠,适用于生产中快速在线检测。     

近红外在线检测丹红注射液醇沉过程中多指标成分的含量变化

目的运用近红外光谱分析技术(NIR)在线检测丹红注射液醇沉过程中多指标成分的含量变化,包括丹参素、原儿茶醛、迷迭香酸、丹酚酸B和乙醇浓度。方法以HPLC和气相色谱法分别测定4种指标成分和乙醇浓度的含量,作为参考值,并与NIR光谱数据关联,运用偏最小二乘回归(PLSR)法建立NIR定量校正模型,并将模型用于在线检测丹红注射液醇沉过程。结果模型测量校正集样本的丹参素、原儿茶醛、迷迭香酸、丹酚酸B和乙醇浓度的相对分析误差(RPD)分别为5.72%,7.46%,8.44%,4.41%和5.50%,相关系数(R2)分别为0.969 5,0.982 0,0.985 9,0.948 4和0.967 0,验证集相对偏差RSEP分别为5.35%,7.59%,6.42%,4.51%和2.30%。结论 NIR光谱分析技术可作为一种丹红注射液大生产中醇沉过程的在线分析方法。     

NIR结合OPUS软件建立山药中尿囊素定量模型

目的：利用近红外光谱（NIR）结合OPUS软件直接测定山药中尿囊素的含量。方法：对山药样品进行近红外光谱检测并采用高效液相色谱（HPLC）法测定其尿囊素的含量，结合OPUS软件建立NIR光谱特征值与HPLC测定的结果之间的校正模型，进而对预测集样品进行分析。结果：校正样品集经内部交叉验证建立校正模型，内部交叉验证决定系数R^2=95．47，对预测集样品进行外部验证，预测值与真实值的相关系数R^2=95．98。结论：利用NIR技术测定山药样品中尿囊素的含量是可行的，为山药药材的质量控制提供一种快速简便的检测方法。     

近红外光谱法快速分析硝酸甘油片的含量

目的:建立测定硝酸甘油片含量的近红外光谱(NIR)快速分析方法。方法:以全国不同企业生产的硝酸甘油片为分析对象,用光纤探头在12000~4000 cm-1光谱范围内测定近红外漫反射光谱;以校正均方差(RMSEC)和相关系数(R2)为指标,通过筛选,确定了用于建模的最优近红外波段和光谱预处理方法,建立了近红外光谱与HPLC分析值之间的校正模型,并以此预测了15个未知样本。定性鉴别方法为马氏距离与限定值相比较。结果:定量模型的浓度范围为0.552%~1.581%g.g-1,相对标准偏差小于8%,定性鉴别方法可将硝酸甘油片与其他硝酸酯类片剂及安慰剂相区别。结论:该方法快速、简便,具有一定的专属性,可用于药物的快速检验。     

基于高光谱技术的灵芝孢子粉破壁率快速检测方法研究

目的 以破壁灵芝孢子粉为研究对象,利用高光谱技术结合化学计量学建立了灵芝孢子粉破壁率快速无损检测方法。方法 首先,采集不同破壁率灵芝孢子粉样品的高光谱图像,选定感兴趣区域后计算获得各样品可见-短波近红外波段(397-1004 nm)范围内的光谱数据;然后,比较了运用标准正态变量变换、多元散射矫正、Savitsky-Golay(SG)平滑、小波变换、SG平滑+标准正态变量变换及SG平滑+多元散射矫正等6种光谱预处理方法,竞争性自适应重加权、连续投影算法、无信息变量选择、最小角回归、遗传算法等5种特征波段提取方法以及偏最小二乘法、支持向量机、极限学习机、多层感知机及LightGBM等5种算法所建立的定量校正模型预测性能。结果 获得最优预测性能的算法组合为：SG平滑+竞争性自适应重加权特征波段选择+偏最小二乘;基于该算法组合建立的定量校正模型在破壁率区间为90%-100%的灵芝孢子粉样品预测集决定系数为0.8682、均方根误差为0.0117;进一步,将选定的最优算法组合应用于构建样品破壁率区间为0-100%的定量校正模型,计算测试集决定系数为0.9731,均方根误差为0.0493,表现出良好的泛化能力。结论 所建立的定量检测模型可以实现对灵芝孢子粉破壁率的快速、无损检测,为破壁灵芝孢子粉及其产品的质量控制提供了技术支撑。     

硫酸阿米卡星注射液近红外定量模型及一致性检验方法的建立

目的利用近红外光谱法建立硫酸阿米卡星注射液的定量模型及一致性检验方法。方法采集硫酸阿米卡星注射液近红外(NIR)光谱,采用偏最小二乘法(PLS)进行回归,通过建立NIR光谱与HPLC法测定值之间的多元校正模型,测定硫酸阿米卡星注射液的含量;分别建立本品种4家生产企业的一致性检验方法。结果定量模型的外部验证决定系数R2为75.7,外部验证均方差(RMSEP)为1.08。所建立的一致性检验方法能够对不同企业样品作出较为准确的判断。结论本方法快速、简便、无损,结果准确,适用于药品的现场筛查及样品在流通过程中的质量监控。     

近红外光谱法测定氯霉素注射液含量

目的利用近红外光谱建立快速测定氯霉素注射液含量的方法。方法用抗生素微生物检定法测定氯霉素注射液含量,采用偏最小二乘法(PLS)建立NIR光谱与抗生素微生物检定法测定值之间的多元校正模型,预测氯霉素注射液中氯霉素的含量。结果所建立校正模型内部交叉验证的决定系数为98.01,内部交叉验证均方差(RMSECV)为1.67;外部验证均方差(RMSEP)为2.68,决定系数为95.19,外部验证预测值与理论值的相关系数为0.9659,预测值平均回收率为100.3%(RSD=3.2%,n=11)。结论本法操作简便、快速、结果准确,可用于药品检测车的现场快速检测。     

Synthetic Calibration for Efficient Method Development: Analysis of Tablet API Concentration by Near-Infrared Spectroscopy

Near-infrared (NIR) spectroscopy is an important process analytical technology (PAT) tool for rapid characterization of pharmaceutical tablet quality. The time and expense required for calibration development has been a detriment to implementation of PAT sensors. While methods based on generalized least-squares and net analyte signal pure-component projection (PCP) have been demonstrated to be useful tools for efficient spectroscopic calibration, PCP methods are relatively difficult to deploy and maintain in industrial settings. Synthetic calibration based on augmentation of parallel-testing data with artificial interference spectra generated in silico is introduced as a method to achieve efficient NIR calibration using off-the-shelf chemometric algorithms. A method for estimating a slope correction factor using parallel test data is shown. The results of this work demonstrate that, by using efficient calibration methods, accurate quantitative NIR calibration models for characterization of drug tablet quality can be created using only pure-component spectra and production-scale tablet samples.     

Transfer of NIR calibrations for pharmaceutical formulations between different instruments

In order to evaluate how well existing techniques for transferring NIR calibrations perform for solid pharmaceutical formulations, a study on four assays of active ingredients was undertaken. The study included two configurations of dispersive NIR instruments and one Fourier transform (FT) instrument. Three methods for calibration transfer: slope/bias correction, local centring and piecewise direct standardisation (PDS), were tested and evaluated. Our conclusions are that the calibration transfer methods tested can perform equally well. It was shown that it is possible to transfer calibrations between instruments of different configurations or even of different types, without loosing the prediction ability of the calibration. To achieve a good calibration transfer, a larger variation in the content of the active ingredient in the samples and more samples are needed for the slope and bias correction method compared to the local centring method. For PDS to be a successful calibration transfer method, an optimisation of the number of transfer samples and how they are selected together with various factors specific for this method is needed. Local centring is the preferred transfer method as its performance is excellent yet it is simple to perform, no optimisation is needed, only a few transfer samples are required and the transfer samples do not have to vary in their content of the active ingredient.     

内标对比标准曲线法与标准加入对比法的误差分析

目的对内标对比标准曲线法与标准加入对比法的原理与误差进行分析。方法以相对峰面积为指标 ,利用偏微分原理对二种方法进行误差分析。结果对于内标对比标准曲线法在Ai/Ar=0 3～ 3 0区间 ,标准曲线斜率B(b)较大而可获得较高灵敏度。Ai/Ar=a +b时 ,结果误差较小 ;样品相对峰面积越大及其相对测量误差越小 ,以及a越小时 ,分析误差越小。对于标准加入对比法得到了标准加入曲线不通过原点时的定量计算公式 ;当B与b的差值越小 ,或横轴截距 -A/B与 -a/b差值越大 ,以及测定相对峰面积的误差越小时 ,可使分析相对误差越小。结论两种方法在CE定量分析中应用可行 ,而且特别适合进样不能准确控制的色谱定量分析     

Extended multiplicative signal correction and spectral interference subtraction: new preprocessing methods for near infrared spectroscopy.

Near infrared (NIR) spectroscopy spectra can be converted mathematically to precise quantitative information of chemical and physical nature by multivariate calibration. This makes NIR analysis useful for a variety of "difficult" sample types (powders, slurries), more or less without any sample preparation. The paper emphasizes the importance of using prior knowledge for spectral preprocessing of spectral data prior to the linear multivariate calibration modelling. Two new preprocessing methods are presented: extended multiplicative signal correction (EMSC) for elimination of uncontrollable path length or scattering effects, and spectral interference subtraction (SIS) for elimination of known spectral interferences. Determination of toluene in mixtures with benzene and xylene from NIR spectra with gross simulated light scattering effects is used for illustration.     

近红外光谱法应用于蒲黄总灰分的定量预测研究

目的:利用近红外光谱分析技术,建立中药蒲黄总灰分的快速、无损测定方法。方法:采用偏最小二乘回归方法(PLSR)对不同的光谱预处理方法、建模波段和因子数选择等进行比较,建立定量预测模型,并考察模型预测准确度。结果:以一阶导数结合多元散射校正法建立模型,校正模型的相关系数为0.9994,内部交叉验证均方根差(RMSECV)为0.293;交叉检验决定系数(RPD)为29.4,偏移小于0.013。结论:结果表明,总灰分为6.0%～27.3%的10批蒲黄样品的预测值与实测值的相对偏差均小于7.5%。该方法与常规总灰分测定方法比较快速、无损,预测结果准确、可靠,有望推广应用于中药蒲黄的快速检验。     

斜率校正“一测多评法”同时测定杜仲中京尼平苷酸、绿原酸、京尼平苷和松脂素二葡萄糖苷的含量

目的:建立斜率校正"一测多评法"同时测定杜仲中京尼平苷酸(GPA)、绿原酸(CHA)、京尼平苷(GP)、松脂素二葡萄糖苷(PDG)含量的方法。方法:以HPLC法含量测定为基础, CHA为对照,计算GPA、GP、PDG的斜率相对校正因子,并比较斜率校正"一测多评法"与外标法两种结果相关性,从而验证斜率校正"一测多评法"的准确性,最终建立测定杜仲多种活性成分的斜率校正"一测多评法"。结果:在一定的线性范围内,GPA、GP、PDG的斜率相对校正因子分别为:0.7628,0.4786,0.7112,重复性良好。斜率校正"一测多评法"计算的含量值与外标法实测值相关性较好,56批杜仲样本中GPA、GP、PDG含量结果的相关系数均大于0.99。结论:建立的斜率校正"一测多评法"准确性高,可用于杜仲中GPA、CHA、GP、PDG活性成分的含量测定。     

Nondestructive quantitative analysis of erythromycin ethylsuccinate powder drug via short-wave near-infrared spectroscopy combined with radial basis function neural networks.

A new assay method for the nondestructive determination of erythromycin ethylsuccinate powder drug via short-wave near-infrared spectroscopy (NIR) combined with radial basis function (RBF) neural networks is investigated. The modern near-infrared spectroscopy analysis technique is efficient, simple and nondestructive, which has been used in chemical analysis in diverse fields. Short-wave NIR is a more rapid, flexible, and cost-effective method to control product concentration in pharmaceutical industry. The RBF neural networks are local approximation networks that have superiorities in function approximation and learning speed. In addition, the structure of RBF networks is simple. Estimate and calibration of the sample concentration via short-wave NIR are made with the aid of RBF models based on conventional spectra, standard normal variate (SNV), multiplicative scatter correction (MSC) and the first-derivative spectra. Various optimum models of them are established and compared. Experiment results show that the models of SNV spectra can give better performance, and the optimized RBF neural network model after SNV treatment were given, by which the root-mean-square-errors (RMSE) for calibration set and test set were 0.3266% and 0.5244%, respectively and the correlation coefficients (R) for calibration set and test set were 0.9942 and 0.9852, respectively. The proposed RBF method based on short-wave NIR is more valuable and economical for quantitative analysis than traditional methods such as partial least squares (PLS).     

Chemometric and derivative methods as flexible spectrophotometric approaches for dissolution and assaying tests in multicomponent tablets

Two derivative spectrophotometric (ratio derivative spectra and algorithm bivariate calibration) and a chemometric methods (partial least squares, PLS) are proposed for the simultaneous determination of binary mixtures in tablet analysis and dissolutions tests, without prior separation. These approaches are successfully applied to quantify trimethoprim (TMP) combined with sulfamethoxazole (SMX) or sulfamethazine (SMZ) or sulfafurazole (SFZ) using the information in the absorption spectra of appropriate solutions. Beer's law was obeyed in the concentration range of 0.98-17.5 microg/ml for TMP, 0.95-17.2 microg/ml for SMX, 1.16-17.5 microg/ml for SMZ and 0.97-17.4 microg/ml for SFZ. The first derivative (1D) bivariate algorithm method involves the use of four calibration curves: two for each compound at two different wavelengths, selected by Kaiser's method. Similarly, the first derivative ratio spectrophotometry employs the linear relationship between the ratio spectra of the analytes and the concentration range. The results were compared with those obtained by PLS multivariate calibration. The calibration models from PLS were pre-treated by orthogonal signal correction and evaluated by cross-validation using the 'SIMCA-P 9' software. Synthetic mixtures of TMP and sulfonamides were used in five different sets for the validity of the calibrations. Mean recoveries for derivative ratio, derivative bivariate and PLS methods were found to be between 99.7% and 102.0% for TMP, 99.4% and 100.2% for SMX, 99.3% and 101.0% for SMZ and 98.1% and 102.3% for SFZ. The calibrations of the three methods were successfully applied to the assaying and dissolution of placebo and commercial tablets without any prior separation. More than 85% of TMP, SMX and SMZ were dissolved within 15 min. For SFZ, only 85% of the compound was dissolved after 60 min. In this study, the three spectrophotometric methods can be satisfactorily used for the quantitative analysis and for dissolution tests of multicomponent dosage forms.     

Quantitative determination of polymorphic composition in intact compacts by parallel-beam X-ray powder diffractometry II. Data correction for analysis of phase transformations as a function of pressure

An analytical, non-destructive method using parallel-beam transmission powder X-ray diffractometry (PXRD) is presented for in situ whole compact detection and quantification of solid-state phase transformations in powder compacts. Accurate quantification of analyte in intact compacts using PXRD requires a mathematical correction prior to interpolation of calibration data to account for sample differences that result as a function of pressure; namely, compact thickness and solid fraction. Chlorpropamide is examined as a model system, selected because of its susceptibility to polymorphic transformations when consolidated using moderately low pressures. The results indicate that quantification of the transformed phase of chlorpropamide without corrections for solid fraction and thickness, underestimates the extent of transformation by 2.4%. Although the magnitude of the correction for this particular system of polymorphs is small, more significant values are expected for other compounds, particularly those with sufficient compactibility to allow the formation of low solid fraction calibration samples.     

Evaluation of basic algorithms for transferring quantitative multivariate calibrations between scanning grating and FT NIR spectrometers

A key issue in near infrared spectroscopy (NIR) is the possibility to use calibrations generated on one instrument for predictions on others. A number of methods for calibration transfer have been proposed, but which method to choose is typically not straightforward. An evaluation of a number of methods for transferring quantitative calibrations between different instruments was carried out on near infrared diffuse-reflectance data from a pharmaceutical formulation. Six instruments were included in the study, five of which were scanning grating instruments, both with and without fibre-optic probe configuration, and one of which was a Fourier-transform instrument, equipped with a fibre-optic probe. The results show that it is possible to transfer calibrations between different instruments, provided that a structured procedure is used. Simple techniques for calibration transfer, such as slope/bias correction on the predicted results, as well as standard normal variate transformation and local centring of the raw spectra, gave considerably lower prediction errors on transfer than did standardisation with a certified diffuse-reflectance standard, or direct transfer without any transfer function. Notably, including more than one instrument in the calibration also improved the prediction ability of the models on calibration transfer. No significant differences in wavelength scale were found when a certified diffuse-reflectance wavelength standard was measured on the instruments studied. Nor did simulated wavelength scale differences below +/-0.3 nm cause any significant change in the prediction errors.