Identification of hematite particles in sealed glass containers for pharmaceutical uses by Raman microspectroscopy

Raman microspectroscopy has been shown to enable the identification of micro-particles inside sealed glass containers for pharmaceutical use without any sample preparation. Raman spectra were collected from unknown particles with a maximum size of 1mm, adsorbed on the inner surface of ampoules. The particles were clearly identified as primarily hematite with traces of magnetite by their characteristic Raman spectral bands. The presence of this deposit was attributed to the projection of iron oxides during the manufacturing process. These oxide particles were not detected by the quality control process of the glass manufacturer, showing that in-process quality controls failed to detect this problem. Particle identification by Raman microspectroscopy appears to be a selective, rapid and reliable analytical procedure for quality control and assurance in the pharmaceutical industry. Identification of the particles was also helpful for evaluating the nature of the contaminant and enables consequences for the toxicological aspects of final product quality to be managed.     

药物辅料中有毒掺杂物的拉曼/近红外光谱法检测灵敏度评价

目的 建立常用药物辅料(甘油)中有毒掺杂物(二甘醇)的快速检测方法。 方法 利用拉曼/近红外光谱法结合移动窗口相关系数法评价有毒掺杂物的检测灵敏度。 结果 拉曼光谱下获得的检测灵敏度优于近红外光谱,同时移动窗口法可进一步提高检测灵敏度。 结论 拉曼光谱法有望成为现场快速检测药物辅料中掺杂有毒物质的有效方法。     

Quantitative analysis of sulfathiazole polymorphs in ternary mixtures by attenuated total reflectance infrared,near-infrared and Raman spectroscopy

The simultaneous quantitative analysis of sulfathiazole polymorphs (forms I, III and V) in ternary mixtures by attenuated total reflectance-infrared (ATR-IR), near-infrared (NIR) and Raman spectroscopy combined with multivariate analysis is reported. To reduce the effect of systematic variations, four different data pre-processing methods; multiplicative scatter correction (MSC), standard normal variate (SNV), first and second derivatives, were applied and their performance was evaluated using their prediction errors. It was possible to derive a reliable calibration model for the three polymorphic forms, in powder ternary mixtures, using a partial least squares (PLS) algorithm with SNV pre-processing, which predicted the concentration of polymorphs I, III and V. Root mean square errors of prediction (RMSEP) for ATR-IR spectra were 5.0%, 5.1% and 4.5% for polymorphs I, III and V, respectively, while NIR spectra had a RMSEP of 2.0%, 2.9%, and 2.8% and Raman spectra had a RMSEP of 3.5%, 4.1%, and 3.6% for polymorphs I, III and V, respectively. NIR spectroscopy exhibits the smallest analytical error, higher accuracy and robustness. When these advantages are combined with the greater convenience of NIR's “in glass bottle” sampling method both ATR-IR and Raman methods appear less attractive.     

显微共聚焦拉曼检测中药中非法添加的化学降糖药

目的:建立检测中药中非法添加化学降糖药的拉曼光谱法。方法:采用显微共聚焦拉曼光谱法,使样品在显微镜下微区成像,逐点选择不同的点采集拉曼光谱图,并与对照品光谱图进行比对分析,判断是否非法添加。结果:在市场监督抽样的中药中检出非法添加盐酸二甲双胍,检出结果进一步得到HPLC-MS法验证。结论:显微共聚焦拉曼光谱可作为中药、保健食品中非法添加化学药物检测的可选方法。     

International amphibian micronucleus standardized procedure (ISO 21427‐1) for in vivo evaluation of double‐walled carbon nanotubes toxicity and genotoxicity in water

Considering the important production of carbon nanotubes (CNTs), it is likely that some of them will contaminate the environment during each step of their life cycle. Nevertheless, there is little known about their potential ecotoxicity. Consequently, the impact of CNTs on the environment must be taken into consideration. This work evaluates the potential impact of well characterized double‐walled carbon nanotubes (DWNTs) in the amphibian larvae Xenopus laevis under normalized laboratory conditions according to the International Standard micronucleus assay ISO 21427‐1:2006 for 12 days of half‐static exposure to 0.1–1–10 and 50 mg L^?1 of DWNTs in water. Two different endpoints were carried out: (i) toxicity (mortality and growth of larvae) and (ii) genotoxicity (induction of micronucleated erythrocytes). Moreover, intestine of larvae were analyzed using Raman spectroscopy. The DWNTs synthetized by catalytic chemical vapor deposition (CCVD) were used as produce (experiment I) and the addition of Gum Arabic (GA) was investigated to improve the stability of the aqueous suspensions (experiment II). The results show growth inhibition in larvae exposed to 10 and 50 mg L^?1 of DWNTs with or without GA. No genotoxicity was evidenced in erythrocytes of larvae exposed to DWNTs, except to 1 mg L^?1 of DWNTs with GA suggesting its potential effect in association with DWNTs at the first nonacutely toxic concentration. The Raman analysis confirmed the presence of DWNTs into the lumen of intestine but not in intestinal tissues and cells, nor in the circulating blood of exposed larvae. © 2009 Wiley Periodicals, Inc. Environ Toxicol, 2010.     

肺癌组织及癌旁正常组织的显微拉曼光谱研究

目的探讨肺癌组织及癌旁正常组织显微拉曼光谱的不同。方法采用显微拉曼光谱仪对56例肺癌组织与其癌旁正常组织进行了拉曼光谱分析。结果肺癌组织与癌旁正常组织的拉曼光谱有较大区别，48例肺癌组织在1408．4cm^-1和2932．8cm^-1处有特征峰存在，2例在1408．4cm^-1处出现特征峰，6例没有出现特征峰；而其癌旁正常组织均未出现特征峰；肺癌组织的光谱强度均比其癌旁正常组织低的多。结论根据拉曼光谱可以区分肺癌组织与其癌旁正常组织。我们认为拉曼光谱技术在临床医学诊断方面将发挥重要的作用。     

纳米雄黄酸水飞品X射线衍射及拉曼光谱分析

目的:分析纳米雄黄酸水飞品(Realgar nanoparticles processed,NRPP)X射线衍射(XRD)图谱和拉曼光谱的图谱特征,并比较雄黄炮制前后晶形结构的异同。方法:采用X射线衍射法和拉曼光谱法对6批雄黄生品,6批雄黄水飞品,6批纳米雄黄酸水飞品进行测定,确定各样品的物相组成及晶形结构成键情况。结果:XRD分析表明雄黄生品和雄黄水飞品均为β-As_4S_4,纳米雄黄酸水飞品中NRPP1,NRPP5及NRPP6批次为β-As_4S_4,NRPP2,NRPP3及NRPP4批次为β-As_4S_4和α-As S的混合体。拉曼光谱分析表明雄黄生品、雄黄水飞品和纳米雄黄酸水飞品均在360~362,342~344,185~187,164~166 cm~(-1)等波数位置出现了特征性较强的拉曼振动峰。结论:X射线衍射技术与拉曼光谱法相结合,能较好地反映出纳米雄黄酸水飞品的特征吸收峰,可用于纳米雄黄酸水飞品的鉴定与分析。雄黄经常规的水飞法炮制未造成晶型结构的变化,而经纳米化并酸水飞后晶形结构则发生改变。     

Characterization of Mannitol Polymorphic Forms in Lyophilized Protein Formulations Using a Multivariate Curve Resolution (MCR)-Based Raman Spectroscopic Method

Purpose  To develop a novel multivariate curve resolution (MCR)-based Raman spectroscopic method to characterize and quantify five known mannitol solid-state forms in lyophilized protein formulations. Materials and Methods  The multivariate quantitation method was developed based on second derivative Raman spectra of three anhydrous crystalline forms (α-, β-, and δ-mannitol), a hemihydrate and an amorphous mannitol form. The method showed a 5% quantitation limit of mannitol forms in lyophilized model protein formulations. Binary mixtures of β- and δ-mannitol combined with evaluation of the prediction residue were used for the method validation. X-ray powder diffractometry data was used to confirm the existence of mannitol forms in the sample. Results  The various polymorphic forms of mannitol were characterized and quantified based on the Raman spectra of the existing pure forms, and the results are consistent with the X-ray powder diffraction data. This Raman method has been demonstrated for the application of monitoring and controlling of mannitol polymorphic forms in the lyophilized drug products during formulation and process development. It has implications in monitoring and improving the quality of the drug product. Conclusions  An MCR-Raman method has been developed for the quantitative determination of five different mannitol polymorphic forms in the presence of sucrose and protein. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Micro-Raman spectroscopy shows how the coating process affects the characteristics of hydroxylapatite

The diversity in the structural and chemical state of apatites allows implant manufacturers to fine-tune implant properties. This requires suitable manufacturing processes and characterization tools to adjust the amorphous phase and hydroxyl content from the source hydroxylapatite. Hydroxylapatite was processed by high-velocity oxy-fuel spraying, plasma spraying and flame spraying, and primarily analyzed by Raman spectroscopy. Investigation of rounded splats, the building blocks of thermal spray coatings, allowed correlation between the visual identity of the splat surface and the Raman spectra. Splats were heat-treated to crystallize any remaining amorphous phase. The ν₁ PO₄ stretching peak at 950–970 cm^?1 displayed the crystalline order, but the hydroxyl peak at 3572 cm^?1 followed the degree of dehydroxylation. Hydroxyl loss was greatest for flame-sprayed particles, which create the longest residence time for the melted particle. Higher-frequency hydroxyl peaks in flame- and plasma-sprayed splats indicated a lower structural order for the recrystallized hydroxylapatite within the splats. Crystallization at 700 °C has shown potential for revealing hydroxyl ions previously trapped in amorphous calcium phosphate. This work compares Fourier transform infrared and Raman spectroscopy to measure the hydroxyl content in rapidly solidified apatites and shows that Raman spectroscopy is more suitable.     

湿度及摩擦涂布对粘结剂渗入牙本质深度的激光拉曼光谱分析

目的：采用显微激光拉曼光谱仪观测不同湿度及摩擦涂布对粘结剂渗入牙本质深度的研究。方法：选用24颗新鲜第三磨牙,随机均分为6组,去除胎面釉质,在干燥和再湿润脱矿牙本质上分别进行非摩擦涂布（norub－bingaction,NRA）、轻轻摩擦涂布（slightrubbingaction,SRA）、加力摩擦涂布（vigorousrubbingaction,VRA）各10s,光照10S后粘结Chrisma树脂。平行牙本质小管方向片切厚1mm的试件,并将其置于显微激光拉曼光谱仪中,在界面处,每5tzm测量一个点,计算机自动记录拉曼光谱,根据所记录的谱线进行对比、分析。结果：湿润组SRA渗透深度最高,干燥组VRA渗透深度与其相当。结论：显微激光拉曼光谱仪是研究修复粘接界面的有效手段。干燥条件下,粘结剂加力摩擦涂布渗入牙本质的深度与湿润组轻轻、加力摩擦涂布相似。