基于最小二乘支持向量机的苯麻滴鼻液含量测定

应用最小二乘支持向量机（LS-SVM）技术同时测定苯麻滴鼻液中盐酸苯海拉明和盐酸麻黄碱的含量。对苯麻滴鼻液的紫外光谱数据进行预处理和主成分分析后不经分离，采用LS-SVM学习建模，并同时测定两组分的含量。对均匀设计标样中的盐酸苯海拉明、盐酸麻黄碱拟合相关系数分别为0．9999、0．9993。测试样品误差范围-0．81％～3．68％，测定样品平均回收率分别100．0％、99．7％。与HPLC法所得结果无显著差异。     

紫外分光光度法同时测定苯麻滴鼻液的组分含量

目的：应用人工神经网络技术同时测定苯麻滴鼻液中盐酸麻黄碱和盐酸苯海拉明的含量。方法：对苯麻滴鼻液的紫外光谱数据进行预处理和主成分分析后无需分离，采用人工神经网络学习建模，同时测定两组分的含量。结果：对均匀设计标样中的盐酸麻黄碱、盐酸苯海拉明拟和r分别为0．9989与0．9985；测试样品误差范围是1．573％～1，251％与-0，551％～2．827％；测定样品平均回收率分别99．92％，102．11％。结论：人工神经网络可用于苯麻滴鼻液的含量测定分析。     

近红外漫反射光谱法直接测定银杏叶提取物粉末中总黄酮的含量

目的：应用近红外漫反射光谱技术和化学计量学方法，直接测定银杏叶提取物粉末中总黄酮的含量。方法：收集不同含量分布的银杏叶提取物粉末样品，以HPLC法测定其总黄酮的含量，并采集其近红外漫反射光谱数据。应用主成分分析法(PCR)、偏最小二乘法(PLS)、改进偏最小二乘法(MPLS)等回归模型对HPLC测定的结果与近红外漫反射光谱数据进行回归。经内部交叉验证，建立校正模型，进而对预测集样品进行分析。结果：MPLS建立的校正模型的准确性最佳，其预测决定系数(RQS)为0．977。对预测集样品进行外部验证，预测值与真值的相关系数(r^2)达0．973，样品回收率为96．15％—102．0％，RSD为1．1％。结论：建立了一个利用近红外漫反射光谱法直接测定银杏叶提取物粉末中总黄酮含量的新方法。该方法具有快速方便、结果准确的特点，可以应用于银杏提取过程的中间控制和大批量产品的检测。     

基于灰色关联度分析的荜澄茄药材质量评价

目的 评价不同产地荜澄茄药材的质量。方法 收集14个产区荜澄茄药材样品，根据2020年版《中国药典（四部）》检查方法测定水分、总灰分、浸出物，采用高效液相色谱法测定药材样品中柠檬醛和芦丁的含量。以上述5个指标为考察对象，采用灰色关联度分析法构建荜澄茄药材质量评价模型，并与主成分分析法结果比较。结果 灰色关联度分析法结果显示，福建建阳产药材样品与最优参考序列的相对关联度（0.66）最高，质量最优；广西苍梧产药材与最优参考序列的相对关联度（0.30）最低，质量最差。主成分分析法与灰色关联分析法的结果基本一致。结论 所建立模型可用于荜澄茄药材的质量评价，建议将柠檬醛、芦丁含量测定纳入质量标准。     

不同产地丹参药材干燥前后化学成分含量变化

目的为了验证不同产地丹参中丹酚酸类成分是否都是采后干燥诱导的产物,分别测定四川、山东、陕西三个主要产区新鲜样品晒干后主要化学成分含量的变化。方法采用高效液相色谱法测定了新鲜和晒干丹参中6种酚酸和4种丹参酮类成分的含量。结果新鲜丹参样品中丹酚酸类成分含量甚微（丹酚酸B〈0．41％）,但晒干样品中含量显著增加（丹酚酸B≥3．0％）。晒干后样品中丹参酮类成分含量也有明显增加。结论不同产地丹参的重要成分丹酚酸B都是采后干燥胁迫诱导的产物。     

不同产地裸体方格星虫脂肪酸类成分资源化学评价研究

目的 对裸体方格星虫样品中脂肪酸类成分进行比较研究。方法 采用气相色谱-质谱联用技术（GC-MS）对12个裸体方格星虫样品中的26种脂肪酸进行了含量测定,并进一步对各样品中的各成分的含量进行了主成分分析。结果 对裸体方格星虫样品的测定结果显示各样品26种脂肪酸类成分总含量范围为198.20?578.05 ?g/g,总含量最高的样品是海南三亚的裸体方格星虫体腔液样品（S12）;各产地样品中脂肪酸类成分总含量均呈现体腔液部位高于外壁 内脏部位。测定样品的26种脂肪酸中,不饱和脂肪酸总含量高于饱和脂肪酸总含量;多不饱和脂肪酸中,亚油酸和?-亚麻酸含量最高,分别占总含量的1.54%?5.65%和1.61%?4.94%;单不饱和脂肪酸中顺芥子酸含量最高,分别占各样品总含量的14.66%?46.41%;基于26种脂肪酸的含量测定结果对12个裸体方格星虫样品的PCA分析结果显示不同产地裸体方格星虫的外壁 内脏样品相互接近,体腔液样品差别较大。结论 裸体方格星虫中脂肪酸不仅种类多样、含量丰富,而且具有多种重要活性作用的不饱和脂肪酸比例合理。本研究中对脂肪酸类成分的研究结果将对进一步开发利用裸体方格星虫提供一定的理论基础。     

HPLC法测定意比舒乳膏中曲安奈德和硝酸益康唑的含量

意比舒乳膏为外用药 ,用于湿疹性霉菌病、轮廓性湿疹、顽癣、环状疱疹等。其主成分为曲安奈德和硝酸益康唑 ,原标准中只有曲安奈德的含量测定[1 ] ,而另一主成分硝酸益康唑为定性检查。本文采用高效液相色谱法同时测定两种成分的含量[2 ] 。1　仪器和试药岛津ＬＣ 1 0ＡＴｖｐ高效液相色谱仪 ,ＳＰＤ 1 0Ａｖｐ检测仪 ,岛津色谱工作站。曲安奈德和硝酸益康唑对照品 (供含量测定用 ,中国药品生物制品检定所提供 ) ,乙腈 (色谱纯 ) ,重蒸馏水 ,其余试剂为分析纯 ,样品及阴性样品均由贵阳涸德制药有限公司提供。2　方法和结果色谱条件　采用Ｓ…     

气相色谱法测定冰硼散中冰片含量

本文论述了对含冰片制剂的定量分析研究方法。本实验采用GC法对冰硼散中冰片成分进行含量测定，即将待测样品用乙酸乙酯浸提12h以上，以冰片为标准品，萘为内标物，采用内标标准曲线法对样品准确定量。回收率99．90％，相对标准偏差0．51％。该法操作简便快速，结果准确可靠。     

用加校正因子的主成分自身对照法测定苯扎贝特中杂质氯苯酪胺的含量

目的：建立加校正因子的主成分自身对照法测定苯扎贝特中杂质氯苯酪胺的含量。方法：通过方法学验证试验，证明所采用的高效液相色谱法外标法测定苯扎贝特中杂质氯苯酪胺的含量方法可行；再利用外标法，分别测定主成分苯扎贝特和杂质氯苯酪胺的保留时间，计算氯苯酪胺相对于苯扎贝特的相对保留时间，分别测定主成分苯扎贝特和杂质氯苯酪胺的线性方程，以斜率计算杂质氯苯酪胺相对于主成分苯扎贝特的校正因子；最终利用相对保留时间确定杂质氯苯酪胺的位置，用校正因子测定杂质氯苯酪胺的含量。结果：测得杂质氯苯酪胺相对于主成分苯扎贝特的相对保留时间为0．90，校正因子为1．2494。结论：用加校正因子的主成分自身对照法测定苯扎贝特中杂质氯苯酪胺的含量，方法可行。     

乘子法测定复方替硝唑含漱液中二组分的含量

目的：用乘子法同时测定复方替硝唑含漱液中二组分的含量。方法：用乘子法的原理和计算步骤处理多波长吸收度数据。结果：模拟样品中醋酸氯已定、替硝唑的平均回收率分别为99．75％，100．17％，RSD分别为0．73％，0．42％（n=10），对3个批号实际样品的测定结果与标准方法吻合。结论：与标准方法相比．该方法具有简便、快速、易于实现自动分析的优点。     

Moisture determination in hygroscopic drug substances by near infrared spectroscopy

The moisture level in a hygroscopic drug substance was successfully determined by near infrared spectroscopy using coulometric Karl Fischer titration as the reference method. The importance of sample handling and proper application of the reference technique are stressed for this difficult sample type. Samples were prepared with moisture levels from 0.5 to 11.4% (w/w) and reflectance spectra were collected over the spectral range 1100–2500 nm. Calibration models were built using partial least squares (PLS) regression analysis. Optimum models were found by choosing proper spectral ranges and number of PLS factors. The best calibration models were built using first derivative spectra, a spectral range of 1850–1936 nm and 5 PLS factors. The corresponding standard error of prediction was 0.11% (w/w) water.     

Rapid quantification of phenolic acids in Radix Salvia Miltrorrhiza extract solutions by FT-NIR spectroscopy in transflective mode

A rapid method for simultaneous determination of main phenolic acids in Radix Salvia Miltrorrhiza extract solutions was developed using Fourier transform near infrared spectroscopy in transflective mode and multivariate calibration and HPLC-UV as the reference method. Partial least squares (PLS) algorithm was conducted on the calibration of regression models. The multiplicative scatter correction, Norris derivative and second derivative were adopted for the spectral pre-processing, and the number of PLS factors were optimized by leave-one-out cross-validation. The performance of the final model was evaluated according to root mean square error of prediction (RMSEP) and correlation coefficient (R). The R values achieved in the prediction set were above 0.93. The developed models were used for analysis of unknown samples and routine monitoring with satisfactory results. This work demonstrated that NIR spectroscopy combined with PLS algorithm could be used for the rapid determination of the main phenolic acids of Salvia Miltrorrhiza extract solutions.     

Application of near infrared spectroscopy for rapid analysis of intermediates of Tanreqing injection

A method for rapid quantitative analysis of four kinds of Tanreqing injection intermediates was developed based on Fourier transform near infrared (FT-NIR) spectroscopy and partial least squares (PLS) algorithm. The NIR spectra of 120 samples were collected in transflective mode. The concentrations of chlorogenic acid, caffeic acid, luteoloside, baicalin, ursodesoxycholic acid (UDCA), and chenodeoxycholic acid (CDCA) were determined with the HPLC–DAD/ELSD as reference method. In the PLS calibration, the NIR spectra were pretreated with different methods and the number of PLS factors used in the model calibration was optimized by leave-one-out cross-validation. The performance of the final PLS models was evaluated according to the root mean square error of calibration (RMSEC), root mean square error of cross-validation (RMSECV), root mean square error of prediction (RMSEP), BIAS, standard error of prediction (SEP), and correlation coefficients (R). The R values in the prediction sets were all higher than 0.93, and the SEPs for the 6 compounds are 1.18, 6.02, 2.71, 155, 126, 30.0 mg/l, respectively. The established models were used for the liquid preparation process analysis of Tanreqing injection in three batches, and a model updating method was proposed for the long-term usage of the established models. This work demonstrated that NIR spectroscopy is more rapid and convenient than the conventional methods to analyze the intermediates of Tanreqing injection, and the presented method is helpful to the implementation of process analytical technology (PAT) in pharmaceutical industry of Chinese Medicines Injections.     

Robust calibration design in the pharmaceutical quantitative measurements with near-infrared (NIR) spectroscopy: Avoiding the chemometric pitfalls

Quantification analysis with near-infrared (NIR) spectroscopy typically requires utilizing chemometric techniques, such as partial least squares (PLS) method, to achieve the desired selectivity. This article points out a major limitation of these statistical-based calibration methods. The limitation is that the techniques suffer from the potential for chance correlation. In this article, the impact of chance correlation on the robustness of PLS model was illustrated via a pharmaceutical application with NIR to the content uniformity determination of tablets. The procedure involves evaluating the PLS models generated with two sets of calibration tablets incorporated with distinct degree of concentration correlation between the active pharmaceutical ingredient (API) and excipients. The selectivity and robustness of the two models were examined by using a series of data sets associated with placebo tablets and tablets incorporated with variations from excipient content, hardness and particle size. The result clearly revealed that the strong correlation observed in the PLS model created by the correlated design was not solely based on the API information, and there was an intrinsic difference in the variances described by the two calibration models. Diagnostic tools that enable the characterization of the chemical selectivity of the calibration model were also proposed for pharmaceutical quantitative analysis.     

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。     

Simultaneous diffuse reflectance infrared determination of clavulanic acid and amoxicillin using multivariate calibration techniques

A method for simultaneous determination of clavulanic acid (CA) and amoxicillin (AMO) in commercial tablets was developed using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and multivariate calibration. Twenty-five samples (10 commercial and 15 synthetic) were used as a calibration set and 15 samples (10 commercial and 5 synthetic) were used for a prediction set. Calibration models were developed using partial least squares (PLS), interval PLS (iPLS), and synergy interval PLS (siPLS) algorithms. The best algorithm for CA determination was siPLS model with spectra divided in 30 intervals and combinations of 2 intervals. This model showed a root mean square error of prediction (RMSEP) of 5.1 mg g(-1). For AMO determination, the best siPLS model was obtained with spectra divided in 10 intervals and combinations of 4 intervals. This model showed a RMSEP of 22.3 mg g(-1). The proposed method was considered as a suitable for the simultaneous determination of CA and AMO in commercial pharmaceuticals products.     

Quantitative solid-state analysis of three solid forms of ranitidine hydrochloride in ternary mixtures using Raman spectroscopy and X-ray powder diffraction

The aim of the study was to develop a reliable quantification procedure for mixtures of three solid forms of ranitidine hydrochloride using X-ray powder diffraction (XRPD) and Raman spectroscopy combined with multivariate analysis. The effect of mixing methods of the calibration samples on the calibration model quality was also investigated. Thirteen ternary samples of form 1, form 2 and the amorphous form of ranitidine hydrochloride were prepared in triplicate to build a calibration model. The ternary samples were prepared by three mixing methods (a) manual mixing (MM) and ball mill mixing (BM) using two (b) 5 mm (BM5) or (c) 12 mm (BM12) balls for 1 min. The samples were analyzed with XRPD and Raman spectroscopy. Principal component analysis (PCA) was used to study the effect of mixing method, while partial least squares (PLS) regression was used to build the quantification models. PCA score plots showed that, in general, BM12 resulted in the narrowest sample clustering indicating better sample homogeneity. In the quantification models, the number of PLS factors was determined using cross-validation and the models were validated using independent test samples with known concentrations. Multiplicative scattering correction (MSC) without scaling gave the best PLS regression model for XPRD, and standard normal variate (SNV) transformation with centering gave the best model for Raman spectroscopy. Using PLS regression, the root mean square error of prediction (RMSEP) values of the best models were 5.0–6.9% for XRPD and 2.5–4.5% for Raman spectroscopy. XRPD and Raman spectroscopy in combination with PLS regression can be used to quantify the amount of single components in ternary mixtures of ranitidine hydrochloride solid forms. Raman spectroscopy gave better PLS regression models than XRPD, allowing a more accurate quantification.     

酚咖片中对乙酰氨基酚和咖啡因的近红外漫反射光谱法测定

建立了近红外漫反射光谱法测定酚咖片中对乙酰氨基酚和咖啡因的含量.以HPLC法所得结果作参比,采用偏最小二乘(PLS)回归法建立了一阶导数光谱与两组分含量间的定量校正模型.并从光谱范围、导数光谱及PLS主因子阶数对模型进行了优化.     

Design of active analogues of a 15-residue peptide using D-optimal design,QSAR and a combinatorial search algorithm

This report describes the rational design of novel analogues of a 15-residue antibacterial peptide CAMELO. A constrained D-optimal design was carried out to derive a training set of 60 analogues. Partial least squares (PLS) models describing quantitative structure-activity relationships (QSARs) were initially derived for the peptides using two published and one novel parameter set. The novel ‘Design parameters’ were based on key structural features identified in hypothetical models of the mechanisms by which peptides interact with cell membranes. In an extension of the PLS method, influence statistics were used to decrease the weighting of compounds having a large effect on model predictions. A combinatorial search algorithm was developed which used PLS models as predictors to select a test set of 39 peptides with high predicted potencies. Within this set, the most potent analogue CAMEL135, which contained seven point mutations from CAMEL0, was identified. For a panel of 24 bacteria, the mean MIC value of CAMEL135 was approximately half of that for CAMEL0. For the parameter sets tested, covariance functions derived from Z-scales gave highest Q²-values for the training set, whilst the model using the the ‘Design parameters’ gave least error when predicting the activity of the test set. The predictive ability of a third published set of peptide parameters was found to compare favourably with that of the parameters used in the design. Analysis of the PLS models indicates that hydrophobicity and amphipathicity are the most important features influencing activity for this class of compound. © Munksgaard 1997.     

人血白蛋白的激光拉曼光谱法测定

建立了激光拉曼光谱法测定人血白蛋白溶液。采用一元线性回归法及偏最小二乘法建立定量分析模型,人血白蛋白在48.8～243 g/L(4.88%～24.30%)浓度范围内线性关系良好。两种方法的r均为0.999 7,交叉验证均方差(RMSECV)为0.385和0.153。