朱砂中添加5种色素的鉴别研究

目的：建立以薄层色谱为初筛,高效液相色谱验证相结合的方法,以补充检验朱砂药材中非法添加颜料红531、颜料红571、酸性红73、偶氮玉红、胭脂红5种色素。方法：采用薄层色谱法,硅胶G为固定相,70%乙醇为溶剂,正丁醇-乙醇-冰乙酸-水（8∶4∶2∶2）为展开剂,在可见光下检视筛查。采用高效液相色谱法（HPLC）,以十八烷基硅烷键合硅胶为填充剂,流动相为乙腈-0.02 mol·L^-1醋酸铵梯度洗脱,柱温30℃,检测波长237 nm,用二极管阵列检测器进行检测,通过与颜料红531、颜料红571、酸性红73、偶氮玉红、胭脂红对照试剂色谱峰比对加以确证,以液质联用对结果加以验证。结果：在薄层色谱和HPLC验证结果一致情况下,68批朱砂样品中,有8批样品分别含有上述1种或几种色素添加。结论：该方法简单、快速、重复性好、成本低,补充了朱砂饮片国家药品标准中的相关规定,对进一步加大对中药材中药饮片市场的监管以及开展染色掺假中药专项整治具有较强的实用性。     

壳聚糖类医疗器械非法添加尼泊金酯类及甲硝唑的测定

摘 要 目的：对壳聚糖类医疗器械产品非法添加的抑菌药物尼泊金酯及甲硝唑进行测定。方法: 采用高效液相色谱法,色谱柱：ZORBAX Eclipse XDB C18柱（250 mm×4.6 mm, 5 μm）,流动相：水-乙腈（65∶35）,流速1.0 ml·min^-1,检测波长：254 nm,柱温：35℃,进样体积：10 μl。结果: 栓剂及凝胶剂壳聚糖样品检出尼泊金乙酯,洗剂样品检出甲硝唑。结论:该方法快速,简便,对于全面深入考察壳聚糖类医疗器械产品的非法添加抑菌药物情况具有指导性意义。     

我国中药红花的质量问题和监管策略

目的：通过检验和监管工作中发现的问题,对当前红花市场质量状况进行分析,为红花的质量监管及临床用药提供建议。方法：在全国范围内进行抽样检查,依据红花现行标准对抽验样品进行检验。统计分析检验数据及其存在的质量问题。结果：检验发现部分样品有染色现象。结论：染色的目的是掩盖药材的质量问题;非法加入的色素和染料,特别是一些化工合成染料的安全性风险较高,染色行为严重危害公众用药质量和安全。提升红花药材及饮片的质量,需要注重源头治理和可追溯体系建设,加强生产、流通、使用领域的监管,保障公众用药安全和有效。     

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。     

人参再造丸中非法添加松香酸的检查方法

摘 要 目的：建立人参再造丸中非法添加松香酸的HPLC检查方法。 方法: 采用Thermo Hypersil GOLD C18色谱柱（250 mm×4.6 mm,5 μm）,以乙腈 0.1%甲酸（82∶18）为流动相等度洗脱,检测波长为241 nm（全波长扫描范围为190～400 nm）, 柱温为30 ℃,流速为1.0 ml·min-1,进样量为10 μl。通过比对供试品与对照品HPLC色谱及光谱,对人参再造丸中是否非法添加松香酸作定性分析,并利用超高效液相色谱 质谱（UPLC MS）联用技术对阳性检出样品进行验证。 结果: 本方法可检出松香酸,检出限为0.99 μg·g-1。 结论: 该方法简便快速、灵敏度高、准确可靠,可用于人参再造丸中非法添加松香酸的检查。     

基于指纹图谱的女金丸质量一致性评价

目的 分别建立女金丸的高效液相色谱(HPLC)和气相色谱(GC)指纹图谱,客观评价女金丸的产品质量一致性。方法 采用Agilent Eclipse plus C₁₈（4.6 mm×250 mm,5 μm）色谱柱,乙腈(A)-0.2%甲酸溶液(B)为流动相,梯度洗脱(0~25 min,10% A~35% A;25~37 min,35% A~59% A;37~40 min,59% A~75% A), 柱温和流速分别为30 ℃和1 mL·min^-1,波长切换,0~20 min,230 nm;20~40 min,270 nm,建立女金丸的HPLC指纹图谱;采用HP-5毛细管柱(30 m×250 mm×0.25 mm),升温程序为初始温度50 ℃,保持1 min,以每分钟20 ℃的速率升温至130 ℃,保持10 min;再以每分钟2 ℃的升温速率升至180 ℃,保持1 min;进样口温度230 ℃,检测器温度250 ℃;分流进样,分流比10︰1,建立女金丸的气相色谱指纹图谱。采用高分辨质谱和对照品对指纹图谱中的特征峰进行确认,并通过《中药色谱指纹图谱相似度评价软件》（2012年版）对指纹图谱进行相似度计算,来评价女金丸的产品质量一致性。结果 共确定女金丸高效液相色谱指纹图谱15个共有峰,通过对照品比较指认其中12个成分;共确定女金丸气相色谱指纹图谱30个共有峰,通过高分辨质谱和对照品比较指认其中28个成分。不同企业之间和同一企业内部产品质量一致性较差。结论 所建立的女金丸高效液相色谱和气相色谱指纹图谱信息较为全面,可用于女金丸的产品质量一致性评价。     

苋菜红小鼠骨髓微核试验

目的：用骨髓微核试验观察苋菜红对小鼠的毒性反应,为进一步致突变研究提供参考。方法：试验动物随机分5组,分别为阴性对照组,苋菜红低、中、高3个剂量组和阳性对照组。每组10只动物,雌雄各5只。连续ig给予不同剂量的苋菜红,观察试验期内小鼠的一般毒性症状、体质量增长情况和骨髓细胞微核率的改变。结果：实验期间动物的精神、外观均无异常。苋菜红高剂量组动物体质量在给药第2～3天下降,中、低剂量组动物体质量未见异常。苋菜红剂量在500～2 000 mg/kg对小鼠骨髓微核率无明显影响。结论：苋菜红对小鼠骨髓细胞无明显致突变作用。     

基于HPLC-MS/MS法的脑灵素制剂中人参掺伪检查研究

目的 建立脑灵素制剂中人参掺伪检测方法。方法 高效液相色谱法-串联电喷雾三重四级杆质谱法（HPLC-MS/MS）,采用Aglient ZORBAX EclipsePlus C₁₈色谱柱（2.1 mm×100 mm,1.8 µm）,以乙腈-水为流动相,流速为0.35 mL·min^-1;柱温为40 ℃,进样量为5 µL,多反应监测（MRM）模式。结果 66批脑灵素制剂样品中,有36批样品检出拟人参皂苷F11成分,检出率为54.5%。结论 脑灵素制剂中存在人参掺伪使用的现象,本方法准确可靠,可为脑灵素制剂中人参质量控制提供参考。     

丁香掺杂染色问题及检测方法研究

目的：4-甲基咪唑为焦糖色素制备过程中的一副产物,通过建立4-甲基咪唑的快速检测方法,控制丁香中花梗染焦糖色素后掺入样品。方法：采用高效液相色谱-质谱联用法,色谱柱为PhenomenexLuna C18（2 mm×150 mm,3μm）,以甲醇-0.1%甲酸溶液为流动相梯度洗脱,流速0.3 mL·min^-1,柱温30℃;质谱使用电喷雾离子源,正离子模式下检测。结果：4-甲基咪唑在9.28~371.11 ng·mL^-1浓度范围内呈良好的线性关系（r=0.9994）,平均回收率96.91%,RSD=1.0%;160批次丁香中33批次检出4-甲基咪唑,表明上述样品涉嫌染色。结论：本方法快速、简便、准确,专属性强,灵敏度高,可作为丁香中4-甲基咪唑的定性定量检测方法,为控制丁香质量提供参考。     

国家药品评价性抽验通滞苏润江制剂质量分析及建议

目的：通过对通滞苏润江制剂的评价性抽验结果进行分析,以评价其质量现状。方法：先依据现行质量标准进行检验。再采用高效液相色谱法、气相色谱法和化学计量学等分析技术,从安全性、有效性和整体质量控制角度开展探索性研究。结果：标准检验合格率为100%。探索性研究结果表明,部分样品存在辐照问题;部分样品存在黄曲霉毒素检出的情况;毒性成分秋水仙碱的检测方法和限度存在不一致的情况;贵细药西红花普遍投料不足;部分样品番泻叶成分含量低;诃子肉含量差异过大;质量标准检测项目不够全面、不统一等。结论：通滞苏润江制剂总体质量较差,质量标准有待进一步提高。     

Influence of synthetic and natural food dyes on activities of CYP2A6, UGT1A6, and UGT2B7

Synthetic or natural food dyes are typical xenobiotics, as are drugs and pollutants. After ingestion, part of these dyes may be absorbed and metabolized by phase I and II drug-metabolizing enzymes and excreted by transporters of phase III enzymes. However, there is little information regarding the metabolism of these dyes. It was investigated whether these dyes are substrates for CYP2A6 and UDP-glucuronosyltransferase (UGT). The in vitro inhibition of drug-metabolizing enzymes by these dyes was also examined. The synthetic food dyes studied were amaranth (food red no. 2), erythrosine B (food red no. 3), allura red (food red no. 40), new coccine (food red no. 102), acid red (food red no. 106), tartrazine (food Yellow no. 4), sunset yellow FCF (food yellow no. 5), brilliant blue FCF (food blue no. 1), and indigo carmine (food blue no. 2). The natural additive dyes studied were extracts from purple sweet potato, purple corn, cochineal, monascus, grape skin, elderberry, red beet, gardenia, and curthamus. Data confirmed that these dyes were not substrates for CYP2A6, UGT1A6, and UGT2B7. Only indigo carmine inhibited CYP2A6 in a noncompetitive manner, while erythrosine B inhibited UGT1A6 (glucuronidation of p-nitrophenol) and UGT2B7 (glucuronidation of androsterone). In the natural additive dyes just listed, only monascus inhibited UGT1A6 and UGT2B7.     

阴离子交换固相萃取-HPLC快速测定中药材中合成色素的方法研究

目的：针对中药材染色现象,建立快速测定中药材中亮蓝、柠檬黄、日落黄、赤藓红、苋菜红、诱惑红等6种合成色素的HPLC检测方法。方法：样品用甲醇-0.1%甲酸溶液提取后,再经阴离子固相萃取去除大部分基质干扰,采用Agilent C18色谱柱（4.6mm×250mm,5μm）,以甲醇-20mmol/L乙酸铵为流动相,梯度洗脱,以二极管阵列检测器测定。结果：在山茱萸、黄柏两种基质中,这6种色素在0.1μg/L至100μg/L范围内线性关系良好。检测限为0.16～1.04mg/kg,回收率为80.5%～102.9%,相对标准偏差为1.6%～4.8%。结论：本方法操作简单,结果准确可靠,重现性好,适用于中药材中多种人工色素的快速检测。     

Simultaneous determination of some common food dyes in commercial products by digital image analysis

A simple and relatively fast image-analysis method using digital images, obtained with a flatbed scanner, has been described. The method was used for the simultaneous determination of four common food dyes, namely, carmoisine, brilliant blue, sunset yellow, and quinoline yellow, in binary mixtures in commercial products without a need for any prior separation steps. The results obtained were validated against a standard high-performance liquid chromatography method and a good agreement was obtained. The parameters affecting the experimental results were optimized. Under the optimal conditions, the method provided acceptable linear ranges (20–250 mg/L) with correlation coefficients higher than 0.998, suitable precision (relative standard deviation ≤ 4.5%), and limits of detection between 4.82 and 8.05 mg/L.     

Lack of genotoxic effect of food dyes amaranth,sunset yellow and tartrazine and their metabolites in the gut micronucleus assay in mice

The food dyes amaranth, sunset yellow and tartrazine were administered twice, at 24 h intervals, by oral gavage to mice and assessed in the in vivo gut micronucleus test for genotoxic effects (frequency of micronucleated cells) and toxicity (apoptotic and mitotic cells). The concentrations of each compound and their main metabolites (sulfanilic acid and naphthionic acid) were measured in faeces during a 24-h period after single oral administrations of the food dyes to mice. Parent dye compounds and their main aromatic amine metabolites were detected in significant amounts in the environment of colonic cells. Acute oral exposure to food dye additives amaranth, sunset yellow and tartrazine did not induce genotoxic effect in the micronucleus gut assay in mice at doses up to 2000 mg/kg b.w. Food dyes administration increased the mitotic cells at all dose levels when compared to controls. These results suggest that the transient DNA damages previously observed in the colon of mice treated by amaranth and tartrazine by the in vivo comet assay [Sasaki, Y.F., Kawaguchi, S., Kamaya, A., Ohshita, M., Kabasawa, K., Iwama, K., Taniguchi, K., Tsuda, S., 2002. The comet assay with 8 mouse organs: results with 39 currently used food additives. Mutat. Res. 519, 103–119] are unable to be fixed in stable genotoxic lesions and might be partly explained by local cytotoxicity of the dyes.     

Can the upper inner side of the thigh become a new option for insulin injection?

Objective: Sites for subcutaneous insulin injections include the upper arms, abdomen, buttocks and outer sides of the thigh. No similar study has explored the feasibility of using the inner side of the thigh for insulin injection, since the 4?mm pen needles were introduced for clinical use. This study aimed to determine whether the inner side of the thigh is suitable for insulin injection.

Research design and methods: Seventy-five patients with diabetes under insulin therapy from the Inpatient Department of Endocrinology were recruited for this non-blinded, non-randomized observational study. Subcutaneous adipose layer thicknesses of the upper, middle and lower area of the inner and outer thighs of 35 patients were measured by ultrasound, distance from the skin surface to the femoral deep vessels in 20 patients was measured, and insulin was injected at the upper inner and outer sides of the thigh in 20 patients. Pain perception, bleeding or bruising, leakage at the injection sites, blood glucose changes after insulin injection, and preferred ratings of the patients were measured.

Clinical trial registration: ClinicalTrials.gov NCT02307968.

Results: Subcutaneous adipose layer thicknesses at both the upper inner and outer thighs were more than 4?mm and the minimum distance was 10?mm. Among the 100 injections at the upper inner thigh, only three incidents of perceived pain occurred. No bleeding or bruising and leakage were observed from the inner or outer sides. Furthermore, the difference in blood glucose control between insulin injections at the inner side and outer sides was not statistically significant. Patient ratings for injections at the inner side were similar to injections at the outer side. The key limitation of this study was the small sample size of adult patients as well as the non-randomized controlled design of this study.

Conclusion: The upper inner thigh might be a new option for insulin injection rotation.     

Chitosan citrate as film former: compatibility with water-soluble anionic dyes and drug dissolution from coated tablet

Chitosan citrate solution containing 25% w/w propylene glycol was prepared and tested for its compatibility with some water soluble anionic dyes. The immiscibility between erythrosine, ponceau 4R, sunset yellow or tartrazine solutions and chitosan citrate solution was evident. The Fourier transform-infrared spectra revealed charged interaction between anionic dye and chitosan. Brilliant blue and green FS at concentration of 0.02-1.00% w/w polymer could be miscible with chitosan citrate solution due to the decrease in charge interaction by the positive charge on molecule of brilliant blue, which was also the composition in green FS. Propranolol HCl tablets coated with these colored film-coating solutions exhibited good appearance and no color migration. Drug dissolution from coated tablets was pH dependent, corresponding to the ability of chitosan to protonate in the medium. Color incorporation slightly retarded drug dissolution in acidic medium. Drug dissolved from coated tablet colored with brilliant blue was faster than from that colored with green FS. This was because brilliant blue had positive charge and more SO(3)H groups on its molecular structure, and exhibited higher water solubility. Accelerated condition could alter dissolution characteristics, and the Td+t(0) value from curve fitting between the dissolution profiles and Weibull equation was increased. However, drug dissolution from freshly prepared coated tablets, coated tablets after exposure to accelerated condition and after storage at room temperature for 12 months conformed to the monograph in USP XXIII.     

Studies on the interaction of edible dyes with protein I: Binding parameters of edible dyes with bovine serum albumin

The binding of bovine serum albumin (BSA)-edible dyes was studied by spectrophotometric method. The edible dyes used in this study were amaranth, erythrosine, tartrazine and sunset yellow. The binding free energies and binding sites were determined at pH 7.4. The ranges of edible dye concentration were from 0.3 to 7×10^?5M, and those of BSA were from 0.15 to 3×10^?5M. The binding free energies of BSA-edible dyes were from ?6,300 to ?8,100 cal/mole.     

醒脑再造丸大蜜丸与水蜜丸的体外溶出度比较

目的 建立醒脑再造丸溶出度测定方法,以总黄酮成分为指标比较醒脑再造丸大蜜丸和水蜜丸两种不同剂型的体外溶出差异.方法 应用溶出度测定法第二法桨法,测定大蜜丸和水蜜丸在4个不同溶出介质的累积溶出率,利用紫外分光光度法测定醒脑再造丸两种剂型中总黄酮的含量,比较两种不同制剂的溶出行为.结果水蜜丸在4个溶出介质的累积溶出率分别为51.57%、71.97%、24.73%、50.78%;大蜜丸在4个溶出介质中累积溶出率分别为41.94%、69.82%、16.10%、48.52%.从差异因子和相似因子分析,两种制剂中相同成分的溶出曲线无相似性.结论 本文建立了醒脑再造丸溶出度测定方法,两种制剂中水蜜丸累积溶出率快. 说明在体外溶出方面,水蜜丸这种中药剂型有利于机体对药物的充分吸收,生物利用度高.     

The effects of lutein on cisplatin-induced retinal injury: an experimental study

Aim: Lutein is one of the most common carotenoids defined in human plasma as having potent anti-oxidant effects. We aimed to determine the biochemical and histopathological effects of lutein on cisplatin-induced oxidative retinal injury in rats.

Materials and methods: Twenty-four rats were equally divided into four groups as healthy controls (HC group), only cisplatin (5?mg/kg) administered group (CIS group), Lutein (0.5?mg/kg)?+?cisplatin (5?mg/kg) administered group (LC group), and only Lutein (0.5?mg/kg) (LUT group) administered group. From the blood samples obtained, serum malondialdehyde (MDA), total glutathione (tGSH), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) levels were investigated. In histopathological analyses, the total retinal thickness, retinal pigment epithelium (RPE), photoreceptor layer (PL), outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL), and ganglion cell layer (GCL) were evaluated.

Results: MDA, IL-1β, and TNF-a levels were statistically significantly higher (p?p?Conclusions: Lutein co-administration was highly effective in prevention of cisplatin-induced retinal damage due to the anti-oxidant and anti-inflammatory effects of lutein.