有机纯度标准物质定值技术研究进展

有机标准物质作为参考标准广泛应用于色谱分析领域。有机标准物质化学纯度定值技术是赋予标准物质准确量值的关键。纯度定值技术包括直接测量主组分的方法和扣除杂质的方法。直接测量主组分的方法主要有气相色谱法(GC)、液相色谱法(LC)、定量核磁法(qNMR)、元素分析法和滴定法(重量滴定和容量滴定)。扣除杂质的方法要测量所有可以检测到的杂质组分,然后将其扣除来计算主成分的含量。典型的扣除杂质的方法是凝固点下降法和差示扫描量热法(DSC),并结合水分测量、残留溶剂测量和无机杂质测量进行分析。该文总结了有机标准物质化学纯度的多种定值技术(2000～2012),比较了多种定值技术的优缺点与局限性,并对有机标准物质化学纯度定值技术的发展进行了展望。     

辛基二茂铁同分异构体标准物质的制备

以辛基二茂铁为原材料,利用常压色谱柱结合环糊精包结分离制得(2-辛基)-二茂铁、(3-辛基)-二茂铁、(4-辛基)-二茂铁3种相对纯度均大于99.5%的辛基二茂铁同分异构体,作为标准物质候选物。利用气相色谱法检测,考察标准物质候选物的均匀性和稳定性,用气相色谱–质谱法、核磁共振法分析候选物中杂质的结构,确定其类型。用内标法和主成分自身对照法对不同的杂质进行定值,并对定值不确定度进行评定。(2-辛基)-二茂铁、(3-辛基)-二茂铁、(4-辛基)-二茂铁的纯度分别为99.5%,99.5%,99.8%,扩展不确定度均为0.2%(k=2)。该标准物质可为相关物质的检测提供量值溯源标准。     

气相色谱-质谱法测定眼用全氟丙烷气体中甲醇、甲醛

建立气相色谱–质谱(GC–MS)联用法与气相色谱(GC)法测定眼用全氟丙烷气体中甲醇、甲醛杂质的方法。甲醇采用GC–MS法定性、GC法定量分析,在51.1～511μL/L浓度范围内线性良好(r~2=0.998 5),检出限为4μL/L,测量结果的相对标准偏差为2.73%(n=6),加标回收率为91%～94%;甲醛采用GC–MS定性、定量分析,质谱选择离子(SIM)模式以m/z 29作为甲醛的定量离子,在21.36～106.8μL/L浓度范围内线性良好(r~2=0.999 1),检出限为5μL/L,测量结果的相对标准偏差为3.19%(n=6),加标回收率为89%～94%。该方法灵敏度高,重复性好,简便可行,可用于眼用全氟丙烷气体的质量控制。     

金刚烷胺标准品中纯度受限的杂质分析

为确定购买的金刚烷胺标准品中使纯度受限的主要杂质成分,用质量平衡法对标准品中主成分含量进行定值分析。采用红外光谱、质谱等方法对金刚烷胺标准品的主成分进行定性,用气相色谱–质谱法、顶空气相色谱法、卡尔费休法对其主要杂质进行确证并定量。结果表明金刚烷胺标准品中主要杂质成分为溴代金刚烷胺、甲醇、乙苯和水,含量分别为1.53%,0.0376%,0.0045%,0.41%,经计算金刚烷胺标准品的纯度为98.16%。该方法可用于金刚烷胺标准品主要杂质的定性、定量分析,对其纯度值进行验证。     

间二氯苯纯度的测定

通过测定间二氯苯中的杂质含量得到间二氯苯的纯度。分别采用高效液相色谱法(HPLC–UVD)和气相色谱法(GC–FID)测定间二氯苯中主要杂质邻、对二氯苯的含量,结果表明两种方法所得杂质含量一致;用高效液相色谱法(HPLC)测定间二氯苯中杂质苯的含量,卡尔费休(Karl Fischer)法测定水分含量,热重法(TGA)进行灰分测定,电感耦合等离子体质谱(ICP–MS)法测定无机杂质含量。最终确定间二氯苯的纯度为99.60%,扩展不确定度为0.03%(k=2)。该方法测定结果准确可靠,具有可溯源性。     

盐酸二甲双胍药物中杂质测定方法研究进展

对近年来盐酸二甲双胍类药物中杂质的测定方法进行综述.盐酸二甲双胍类药物中的杂质主要有双氰胺、二甲胺以及由二甲胺形成的亚硝胺类基因毒性杂质等.测定方法主要有高效液相色谱(HPLC)法、离子色谱(IC)法、高效液相色谱–串联质谱(HPLC–MS/MS)法和气相色谱–串联质谱(GC–MS/MS)法,其中高效液相色谱法主要用于...     

GC–MS校准用异辛烷中八氟萘标准溶液的研制

采用重量–容量法研制了气相色谱–质谱(GC–MS)校准用100.1 pg/μL异辛烷中八氟萘溶液标准物质,分别用F检验和回归曲线法对研制的溶液标准物质进行了均匀性和稳定性检验,对定值结果的不确定度进行了评定。结果表明,研制的异辛烷中八氟萘溶液标准物质具有良好的均匀性和稳定性,定值结果的相对扩展不确定度为3%(k=2)。该标准物质可用于GC–MS联用仪的EI源及负CI源的信噪比校准。     

无自身标准样品GC-FID法测定标准物质中有机杂质含量

建立了一种标准物质中有机杂质的无自身标准样品准确定值的GC–FID方法。以与待测有机杂质结构相似的物质作为参考物质校准GC–FID响应信号,采用有效碳数法计算待测杂质的质量响应值Si,检测出样品中该有机杂质的准确含量。以癸二酸二正丁酯纯度标准物质为例,用该法对其中有机杂质总量进行定值,定值结果为0.29%,U=0.07%(k=2)。定值不确定度主要来源于Si和检测重复性。     

磷酸三(2-氯乙基)酯标准物质的研制

研制了有机磷阻燃剂磷酸三(2-氯乙基)酯(TCEP)标准物质。采用硅胶柱层析法对TCEP原料进行纯化,得到纯度大于99%的TCEP纯品。通过红外光谱和气相色谱–质谱准确定性分析后,利用气相色谱法和气相色谱–质谱法结合热重分析法分别对TCEP纯物质进行纯度定值。将制备的50 g TCEP纯品分装到100个小瓶中,每瓶0.5g,从中随机选取10瓶,进行均匀性和稳定性实验,结果表明,研制的TCEP标准物质均匀性良好,在半年内是稳定的。研制的有机磷阻燃剂磷酸三(2-氯乙基)酯标准物质的纯度定值为99.56%,扩展不确定度为1.18%(k=2)。研制的磷酸三(2-氯乙基)酯标准物质满足国家二级标准物质标准的要求。     

GC–MS法分析茵陈挥发油成分

采用水蒸气蒸馏法提取茵陈中挥发性成分挥发油,用气相色谱–质谱联用技术(GC–MS)对茵陈挥发油成分进行分析鉴定,并采用峰面积归一化法测定其相对含量。共检出52种挥发性成分,鉴定了其中31种主要挥发性成分,含量较高的组分为石竹素(15.27%)、(–)-斯巴醇(6.64%)、石竹烯(4.89%)等。GC–MS法适用于茵陈挥发性成分的定性分析,具有灵敏度高、分析速度快的特点。     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

A carbanion induced synthesis of highly congested pyrazole and imidazole containing heterocycles

An efficient approach to the synthesis of highly congested di, penta and hexacyclic pyrazoles as well as imidazole fragment containing novel heterocyclic molecule has been developed through a carbanion induced transformation of suitably functionalized 2H-pyran-2-ones, benzo[h]chromene and thiochromeno[4,3-b]pyrans. Due to the presence of fluorescence, we report their prime application metal sensor as off/on switching in ferric ions.     

Synthesis of pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles by Curtius reaction in Morita-Baylis-Hillman derivatives

Synthesis of substituted pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles from the Morita-Baylis-Hillman derivatives of acrylates via saponification followed by Curtius reaction is described.     

正丁胺对激光染料荧光谱影响的研究

用正丁胺作为碳源,采用射频辉光放电制备碳膜,选用激光染料R6G和聚乙二醇混合液作为蒸气源,采用单源热蒸发,在蒸发室与染料同时沉积得到混合膜,用拉曼光谱和红外光谱分析了碳膜的结构和键合方式,分析表明:碳膜中存在胺基团和氢原子.混合膜的荧光谱测量结果表明,认为正丁胺对染料荧光谱的影响是因为胺基和氢原子的存在.     

Selective synthesis of 4,5-dihydroimidazo- and imidazo[1,5-a]quinoxalines via modified Pictet–Spengler reaction

An efficient tandem approach for the selective synthesis of 4,5-dihydroimidazo[1,5-a]quinoxalines 6a–g and imidazo[1,5-a]quinoxalines 7a–h by the reaction of 2-imidazolyl anilines 4a–c with aryl aldehydes 5a–k under mild reaction conditions is described. Introduction of electron releasing alkyl groups in substrates 4a–b was found to be instrumental for the success of the reaction.     

Understanding the Diels-Alder reactivity of 1,2-azaborine analogues

The Diels-Alder reactivity of 1,2-heteroborines (H₄C₄B(H)X, X?=?NH, PH, AsH; O, S, Se) has been computationally explored by means of Density Functional Theory (DFT) calculations. The influence of the HB?=?X fragment on the reactivity of the system has been quantitatively analyzed in detail by means of the so-called Activation Strain Model (ASM) of reactivity. It is found that the interaction between these species and the dienophile is significantly stronger than that computed for their all-carbon isoelectronic counterpart, benzene. In addition, the strain energy plays a key role in the observed reactivity trends. The role of the aromaticity strength of these heteroarenes on the reactivity is also assessed.