应用近红外光谱和拉曼光谱建立主成分分析模式识别法鉴别不同厂家阿法骨化醇软胶囊

摘 要 目的：比较近红外光谱法和拉曼光谱法对不同厂家阿法骨化醇软胶囊进行模式识别的特点,建立定性模型,并对不同厂家的阿法骨化醇软胶囊进行分析鉴别。方法: 应用近红外光谱与拉曼光谱,首次采用主成分分析的模式识别方法,结合光谱信息分析处方工艺,对不同厂家的阿法骨化醇软胶囊进行近红外光谱和拉曼光谱分析。结果: 近红外光谱法与拉曼光谱法均能提取出阿法骨化醇软胶囊的光谱信息,并进行判别分析。制剂中不同着色剂的荧光效应的影响在拉曼光谱中体现出较大差异。据此,建立了拉曼光谱主成分分析判别模型,前三个主成分重构的三维图中,代表6个不同厂家来源的阿法骨化醇样品点各自聚集,相互区分,实现了正确判别。结论: 利用拉曼光谱与近红外光谱互补性,建立不同工艺的阿法骨化醇软胶囊的识别方法,可用于阿法骨化醇软胶囊工艺一致性的分析。     

基于伸缩移动窗口相似度与贝叶斯法的药品拉曼光谱分析

目的 提出伸缩移动窗口相似度结合贝叶斯法通过拉曼光谱技术对弱主药信号药品的真假进行快速判别。方法 采用伸缩移动窗口相似度方法,以弱主药信号药品的药用活性成分（API）的拉曼光谱峰宽为参照,动态调整窗口的大小。在窗口内,分别计算API的拉曼光谱峰信号与药品拉曼光谱的相似度,以及药品与辅料的拉曼光谱相似度,选择那些突出API拉曼光谱峰信号对弱主药信号药品的拉曼光谱信号有贡献的窗口作为贝叶斯判别模型的变量,进而构建弱主药信号药品真假判别模型。结果 本研究构建的弱主药信号药品真假判别模型对弱主药信号药品的真假准确识别率为94.7%,对验证集样本准确识别率为95.6%。结论 基于伸缩移动窗口相似度与贝叶斯算法构建的贝叶斯判别模型可以对弱主药信号药品的真假进行快速判别。     

拉曼光谱法用于药品注射液标准中鉴别项的探讨

目的:探讨在药品标准中采用拉曼光谱方法作为注射液鉴别项的科学性、可行性和有效性。方法:采用拉曼光谱法,以相应对照品的水溶液的拉曼光谱作为参考光谱,对《中国药典》2010年版二部中采用红外光谱法鉴别的8个注射液品种进行定性鉴别。结果:拉曼光谱法能够对氨茶碱注射液等8个品种进行鉴别。结论:拉曼光谱法用于注射液品种的定性鉴别,具有不需要复杂的样品前处理,可直接测定,准确度高,不受水分干扰等优点,可作为药品标准中一些注射液及其他溶液制剂定性鉴别的方法之一。     

基于D-SERS法表征两性霉素B对白色念珠菌抑制作用的研究

目的 建立动态表面增强拉曼光谱法（D-SERS）快速表征两性霉素B （AMB）对白色念珠菌的抑制作用。方法 采用D-SERS法,选用敏感的白色念珠菌分别与不同浓度的AMB相互作用,在不同的作用时间下,通过考察拉曼位移在656 cm^-1和729 cm^-1处的峰强比和药物浓度之间的关系,分析AMB对白色念珠菌拉曼光谱的影响。结果 在一定药物浓度和作用时间下,峰强比与AMB浓度呈负相关,可用于描述AMB对白色念珠菌的抑制作用,且药物浓度低于其最小抑菌浓度。结论 该方法简便、快捷,实现了AMB对白色念珠菌的快速表征,同时为表征更多药物-病原体相互作用提供了更简单、快速的检测方法。     

激光拉曼光谱法测定中药三七花中非法添加的化学降压药

摘 要 目的：对中药三七花中非法添加的化学药进行快速检测。方法: 采用激光拉曼光谱仪对三七花中添加的化学降压药进行检测,考察其检测限,根据光谱图进行定性分析。结果: 拉曼光谱法可检测出添加于三七花中的化学降压药,三七花中各化学降压药与相应对照品的拉曼谱图特征峰基本一致,检测方法简便,结果准确。结论:拉曼光谱技术可用于三七花中非法添加化学降压药的测定。     

注射用甲磺酸培氟沙星近红外定量分析通用性模型的建立

摘 要 目的：利用近红外光谱法,建立注射用甲磺酸培氟沙星含量快速测定方法。方法: 采集注射用甲磺酸培氟沙星的近红外（NIR）光谱,以矢量归一化法对光谱进行预处理,选择谱段范围为9 176.2~8 169.5 cm^-1、6 051.9~5 716.3 cm^-1和4 509~3 999.9 cm^-1,回归方法为偏最小二乘法（PLS）,建立近红外定量模型。 结果: 经内部交叉验证建立预测模型,浓度范围为7.55%~77.69%,交叉验证均方根（RMSECV）为1.61%,相关系数为0.992 4。结论:建立的近红外定量分析模型可用于注射用甲磺酸培氟沙星快速定量分析。     

薄层色谱-表面增强拉曼光谱法快速检测染色掺伪的西红花

目的 建立一种薄层色谱-表面增强拉曼光谱法对染色掺伪的西红花进行检测。方法 将乙醇溶液润湿的西红花按压在表面喷有银溶胶的薄层板上,然后对按压区域进行表面增强拉曼散射（SERS）检测。依次对润湿剂的浓度、银溶胶的喷洒时间和喷洒量等因素进行优化。结果 成功检测经金胺O、新品红、柠檬黄和胭脂红4种常见染料染色的西红花药材。结论 薄层色谱-表面增强拉曼光谱法可实现对染色西红花简单、快速、灵敏的检测要求,并满足现场快速检测的需求。     

表面增强拉曼光谱法检测保健品中添加的微量西布曲明

摘 要 目的： 对保健品中添加的西布曲明进行快速检测。方法: 用便携式拉曼光谱仪对市场上几种添加了微量西布曲明的保健品进行快速检测,实验条件：激发波长: 785 nm±0.5 nm,光谱覆盖范围: 175～3 100 cm^-1,信号采集时间20 s,光谱分辨率: 8 cm^-1。结果: 研究表明, 表面增强拉曼光谱法可快速检测出添加于保健品中的微量西布曲明,检测结果与传统方法检测的结果相吻合。结论:该方法快速、简便、无损,可作为检测保健品中非法添加的微量西布曲明的快检方法。     

注射用磷霉素钠近红外定量分析通用性模型的建立

摘 要 目的： 利用近红外光谱法,建立注射用磷霉素钠含量快速检定方法。方法: 采集注射用磷霉素钠的近红外（NIR）光谱,建立近红外定量模型。结果: 以矢量归一化和多元散射校正法对光谱进行预处理、选择谱段范围为11 995.8～7 428.9及6 734.6～5 454 cm^-1,回归方法为偏最小二乘法。结论: 该近红外定量分析模型可用于注射用磷霉素钠快速定量分析。     

近红外光谱法鉴别普伐他汀钠片及其原料药晶型的一致性研究

目的 建立全覆盖抽样的普伐他汀钠片的近红外光谱法一致性检验模型,考察制剂工艺的差别和原料药晶型的差异,通过稳健、准确、代表性强的近红外光谱一致性模型实现普伐他汀钠片的快速检验和筛查。方法 对评价性抽验抽取的5个企业中的4个共65批样品建立普伐他汀钠片近红外一致性检验模型,并对4个厂家的原料药的近红外光谱图进行比较。结果 建立了4个厂家普伐他汀钠片剂的近红外一致性模型,预测成功率均为100%;4种原料药和1种无定型粉末的近红外光谱图显示不同晶型光谱图具有差异。结论 近红外光谱法能够用于快速鉴别质量工艺稳定的普伐他汀钠片产品,对制剂工艺进行考察,并能够区分不同晶型的原料药。     

Hydrate formation during wet granulation studied by spectroscopic methods and multivariate analysis

Purpose. The aim was to follow hydrate formation of two structurally related drugs, theophylline and caffeine, during wet granulation using fast and nondestructive spectroscopic methods. Methods. Anhydrous theophylline and caffeine were granulated with purified water. Charge-coupled device (CCD) Raman spectroscopy was compared with near-infrared spectroscopy (NIR) in following hydrate formation of drugs during wet granulation (off-line). To perform an at-line process analysis, the effect of water addition was monitored by NIR spectroscopy and principal components analysis (PCA). The changes in the crystal arrangements were verified by using X-ray powder diffraction (XRPD). Results. Hydrate formation of theophylline and caffeine could be followed by CCD Raman spectroscopy. The NIR and Raman spectroscopic results were consistent with each other. NIR revealed the state of water, and Raman spectroscopy gave information related to the drug molecule itself. The XRPD confirmed the spectroscopic results. PCA with three principal components explained 99.9of the spectral variation in the second derivative NIR spectra. Conclusions. Both CCD Raman and NIR spectroscopic methods can be applied to monitoring of hydrate formation processes. However, NIR is more suitable for monitoring solid-water interactions.     

Hyphenated spectroscopy as a polymorph screening tool

Polymorph screening of a model compound (nitrofurantoin) was performed. Nitrofurantoin was crystallized from acetone-water mixtures with varying process parameters. Two anhydrate forms (alpha and beta) and one monohydrate form (II) were crystallized in the polymorph screen. The solid forms were analyzed with three complementary spectroscopic techniques: near-infrared (NIR) spectroscopy, Raman spectroscopy and terahertz pulsed spectroscopy (TPS), and the results of the solid phase analysis were verified with X-ray powder diffraction (XRPD). NIR and Raman spectroscopy were coupled to achieve a rapid and comprehensive method of solid phase analysis. The hyphenated NIR/Raman spectroscopic data were analyzed with a multivariate method, principal component analysis (PCA). The combination was found effective in screening solid forms due to the complementary characteristics of the methods. NIR spectroscopy is powerful in differentiating between anhydrate and hydrate forms and intermolecular features, whereas Raman spectroscopy is sensitive to intramolecular alterations in the molecular backbone.     

Principles and applications of Raman spectroscopy in pharmaceutical drug discovery and development

Introduction: In recent years, Raman spectroscopy has become increasingly important as an analytical technique in various scientific areas of research and development. This is partly due to the technological advancements in Raman instrumentation and partly due to detailed fingerprinting that can be derived from Raman spectra. Its versatility of applications, rapidness of collection and easy analysis have made Raman spectroscopy an attractive analytical tool.

Areas covered: The following review describes Raman spectroscopy and its application within the pharmaceutical industry. The authors explain the theory of Raman scattering and its variations in Raman spectroscopy. The authors also highlight how Raman spectra are interpreted, providing examples.

Expert opinion: Raman spectroscopy has a number of potential applications within drug discovery and development. It can be used to estimate the molecular activity of drugs and to establish a drug’s physicochemical properties such as its partition coefficient. It can also be used in compatibility studies during the drug formulation process. Raman spectroscopy’s immense potential should be further investigated in future.     

Content uniformity in granules for aceclofenac controlled release (CR) tablets determined using near-infrared spectroscopy and wide area illumination (WAI) raman spectroscopy

Non-destructive and rapid determination methods were developed for aceclofenac controlled release (CR) tablets. The tablet is composed of two layers, rapid release and controlled release (CR) layers. The pharmaceutical manufacturing process for CR granules is very critical for dissolution control of CR tablets. During processing, a rapid and nondestructive method to test content uniformity of aceclofenac granules is required. Chemometrics using near-infrared (NIR) and Raman spectroscopy have found significant uses in quantitative analysis of pharmaceutical products in complex matrixes. Most of the pharmaceutical products can be measured directly with little or no sample preparation using these spectroscopic methods. This study showed NIR and wide area illumination Raman spectroscopy with partial least squares (PLS) was very effective for the content uniformity of granules while high performance liquid chromatography (HPLC), a conventional method, was time-consuming and ineffective for real time control. This study showed that on-line control of content uniformity control of aceclofenac CR tablets can be achieved using NIR and Raman spectroscopy.     

基于近红外光谱的阿立哌唑片溶出行为研究

目的 建立阿立哌唑片剂溶出行为近红外定量模型,预测片剂的溶出行为。方法 采集阿立哌唑片剂近红外光谱,进行溶出度试验,分别于3、6、9、12、15、30 min时测定每片的溶出度,采取卷积平滑方法预处理波段4 000.00～4 396.90 cm^-1和5 326.43～12 000.00 cm^-1的近红外光谱,以偏最小二乘法建立溶出行为模型。结果 不同时间点的校正均方根误差(RMSEC)和预测均方根误差(RMSEP)均在8%以下,不同时间点校正相关系数(R_C)和预测相关系数(R_P)均在0.95以上(6 min的相关系数除外),近红外光谱和各时间点溶出度之间呈现出良好的相关性。结论 近红外光谱分析技术能够预测阿立哌唑片剂的溶出行为,为近红外光谱分析技术在线监测片剂质量奠定了理论基础。     

近红外光谱法测定腰痛宁胶囊中士的宁、马钱子碱和麻黄碱

目的通过考察近红外光谱法对腰痛宁胶囊粉末中士的宁、马钱子碱和麻黄碱的检测,探索一种腰痛宁胶囊生产过程中的快速检测方法。方法采集不同批号腰痛宁胶囊药粉进行近红外光谱检测,以偏最小二乘法建立校正模型,通过该模型与测得的近红外光谱对腰痛宁胶囊中主要成分进行检测。结果经过预处理后的近红外光谱数据与样品中的士的宁、马钱子碱、麻黄碱数据呈现明显的线性关系,各指标的相关系数分别为0.924、0.944、0.874。预测均方差(RMSEP)分别为0.03、0.06、0.02。结论近红外光谱法能快速检测腰痛宁胶囊粉末中士的宁、马钱子碱,可以指导生产过程中的质量控制。     

拉曼光谱快速检测减肥保健品中非法添加酚酞的研究

目的：采用拉曼光谱法快速检测减肥保健品中非法添加的酚酞。方法：本文采用拉曼光谱对减肥保健品中的非法添加物质酚酞进行快速检测,使用适当的溶剂对减肥保健品中可能含有的酚酞进行提取,然后采集提取液的拉曼光谱并进行分析测试。结果：建立了酚酞-甲醇溶液的标准曲线,并且对添加不同浓度酚酞的减肥保健品进行拉曼光谱检测,所得结果与酚酞实际添加量一致。结论：结合简单的前处理方法,拉曼光谱法可对减肥保健品中非法添加的酚酞进行快速检测,并可进行定量分析;该方法快速、简便、成本低、可同时得到定性与定量结果,检测限达到1%。     

Comparison and combination of spectroscopic techniques for the detection of counterfeit medicines

During this study, Fourier transform infrared spectroscopy (FT-IR), near infrared spectroscopy (NIR) and Raman spectroscopy were applied to 55 samples of counterfeit and imitations of Viagra^® and 39 samples of counterfeit and imitations of Cialis^®. The aim of the study was to investigate which of these techniques and associations of them were the best for discriminating genuine from counterfeit and imitation samples. Only the regions between 1800–400 cm⁻¹ and 7000–4000 cm⁻¹ were used for FT-IR and NIR spectroscopy respectively. Partial least square analysis has been used to allow the detection of counterfeit and imitation tablets. It is shown that for the Viagra^® samples, the best results were provided by a combination of FT-IR and NIR spectroscopy. On the other hand, the best results for the Cialis^® samples were provided by the combination of NIR and Raman spectroscopy (1400–1190 cm⁻¹). These techniques not only permitted a clear discrimination between genuine and counterfeit or imitation samples but also the distinction of clusters among illegal samples. This might be interesting for forensic investigations by authorities.