Particle Characteristics’ Influence on FLASH Sintering of Potassium Sodium Niobate: A Relationship with Conduction Mechanisms

The considerable decrease in temperature and time makes FLASH sintering a more sustainable alternative for materials processing. FLASH also becomes relevant if volatile elements are part of the material to be processed, as in alkali-based piezoelectrics like the promising lead-free K_0.5Na_0.5NbO₃ (KNN). Due to the volatile nature of K and Na, KNN is difficult to process by conventional sintering. Although some studies have been undertaken, much remains to be understood to properly engineer the FLASH sintering process of KNN. In this work, the effect of FLASH temperature, T_F, is studied as a function of the particle size and impurity content of KNN powders. Differences are demonstrated: while the particle size and impurity degree markedly influence T_F, they do not significantly affect the densification and grain growth processes. The conductivity of KNN FLASH-sintered ceramics and KNN single crystals (SCs) is compared to elucidate the role of particles’ surface conduction. When particles’ surfaces are not present, as in the case of SCs, the FLASH process requires higher temperatures and conductivity values. These results have implications in understanding FLASH sintering towards a more sustainable processing of lead-free piezoelectrics.     

Sephadex G10凝胶色谱法测定磺苄西林钠中的高分子杂质

目的 建立测定磺苄西林钠中高分子杂质的方法.方法 采用高效液相色谱法,色谱柱为Sephadex G10凝胶柱,流动相A为0.05 mol·L-1的磷酸盐缓冲液(pH7.0)、B为高纯水,流速为1 ml·min-1,检测波长254 nm,柱温为25℃.结果 磺苄西林钠中高分子杂质含量小于0.12%.结论 所建方法灵敏、准确、简便,可用于磺苄西林钠中高分子杂质的质量控制.     

中草药制剂的回收乙醇中杂质的去除方法探讨

目的：探讨中草药制剂的回收乙醇中杂质的去除方法。方法：将回收乙醇进行初步的除杂质实验，选择较好的除杂质方法，再以正交法对其进行优选，并对优选方法加以验证。结果：每1000ml回收乙醇中加入5％高锰酸钾溶液6ml，静置30min，然后加入活性炭6g，再静置30min，滤过，蒸馏，收集蒸馏液作相应的检验，各项指标均能达到规定要求。结论：该方法可有效除去中草药制剂回收乙醇中的杂质，提高其质量。     

Validation of Toxtree and SciQSAR in silico predictive software using a publicly available benchmark mutagenicity database and their applicability for the qualification of impurities in pharmaceuticals

The draft ICH M7 guidance (US FDA, 2013) recommends that the computational assessment of bacterial mutagenicity for the qualification of impurities in pharmaceuticals be performed using an expert rule-based method and a second statistically-based (Q)SAR method. The public nonproprietary 6489 compound Hansen benchmark mutagenicity data set was used as an external validation data set for Toxtree, a free expert rule-based SAR software. This is the largest known external validation of Toxtree. The Toxtree external validation specificity, sensitivity, concordance and false negative rate for this mutagenicity data set was 66%, 80%, 74% and 20%, respectively.This mutagenicity data set was also used to create a statistically-based SciQSAR-Hansen mutagenicity model. In a 10% leave-group-out internal cross validation study the specificity, sensitivity, concordance and false negative rate for the SciQSAR mutagenicity model was 71%, 83%, 77% and 17%, respectively. Combining Toxtree and SciQSAR predictions and scoring a positive finding in either software as a positive mutagenicity finding reduced the false negative rate to 7% and increased sensitivity to 93% at the expense of specificity which decreased to 53%.The results of this study support the applicability of Toxtree, and the SciQSAR-Hansen mutagenicity model for the qualification of impurities in pharmaceuticals.     

Recent advances in trace analysis of pharmaceutical genotoxic impurities

Genotoxic impurities (GTIs) in pharmaceuticals at trace levels are of increasing concerns to both pharmaceutical industries and regulatory agencies due to their potentials for human carcinogenesis. Determination of these impurities at ppm levels requires highly sensitive analytical methodologies, which poses tremendous challenges on analytical communities in pharmaceutical R&D. Practical guidance with respect to the analytical determination of diverse classes of GTIs is currently lacking in the literature. This article provides an industrial perspective with regard to the analysis of various structural classes of GTIs that are commonly encountered during chemical development. The recent literatures will be reviewed, and several practical approaches for enhancing analyte detectability developed in recent years will be highlighted. As such, this article is organized into the following main sections: (1) trace analysis toolbox including sample introduction, separation, and detection techniques, as well as several ‘general’ approaches for enhancing detectability; (2) method development: chemical structure and property-based approaches; (3) method validation considerations; and (4) testing and control strategies in process chemistry. The general approaches for enhancing detection sensitivity to be discussed include chemical derivatization, ‘matrix deactivation’, and ‘coordination ion spray-mass spectrometry’. Leveraging the use of these general approaches in method development greatly facilitates the analysis of poorly detectable or unstable/reactive GTIs. It is the authors’ intent to provide a contemporary perspective on method development and validation that can guide analytical scientists in the pharmaceutical industries.     

Contact allergy to hydrocortisone and thixocortol pivalate: problems in the detection of corticosteroid sensitivity

Several of the difficulties involved in the detection of corticosteroid allergy are illustrated by the problems encountered in a patient sensitive to a preparation containing hydrocortisone and miconazole nitrate. The importance of appropriate concentrations and vehicles for patch testing, the possible role of impurities, and cross-sensitivity of corticosteroid molecules are discussed.     

Problems associated with use of the benzyloxymethyl protecting group for histidines Formaldehyde adducts formed during cleavage by hydrogen fluoride 1

The use of N^α-tert.-butyloxycarbonyl-N^π benzyloxymethylhistidine in peptide synthesis resulted in significant levels of several different side products attributable to the generation of formaldehyde during the hydrogen fluoride cleavage reaction. Methylated impurities in a decapeptide were isolated and identified. These methylated impurities were attributed to the use of the benzyloxymethyl protecting group for the histidines, since the impurities did not form when the dinitrophenyl protecting group was used. Also, peptides containing benzyloxymethyl-protected histidines in addition to N-terminal cysteines quantitatively yielded their respective N-terminal thiazolidine derivatives upon isolation from standard hydrogen fluoride cleavage mixtures. Thiazolidine ring formation was circumvented by including in the cleavage reaction a formaldehyde scavenger such as cysteine hydrochloride or resorcinol.     

HPLC测定头孢西酮钠有关物质

目的:建立高效液相色谱梯度洗脱法测定头孢西酮钠有关物质。方法:采用反相高效液相色谱法,固定相为十八烷基键合硅胶,以流动相为0.02 mol.L-1磷酸二氢铵缓冲液(用0.1 mol.L-1氢氧化钠溶液调pH至5.0)-乙腈梯度洗脱,流速为1 mL.min-1,检测波长278 nm。结果:头孢西酮钠杂质分离良好,检出限0.015μg.mL-1,精密度试验RSD=0.62%。结论:该方法简便、快速,重复性好,可一次性测定头孢西酮钠中的有关物质。     

药物中痕量磺酸酯类物质的检测技术研究进展

烷基磺酸酯和芳基磺酸酯类化合物作为潜在性基因毒性杂质,严重威胁人类健康,因此需要控制食品及药品中磺酸酯的限度。主要介绍了磺酸酯类物质的痕量分析检测技术手段,如GC-MS、HPLC-MS、NMR等,同时阐述了各种检测技术的优缺点。另外,还论述了这些杂质产生的条件,从而提出了避免生成该类杂质的具体措施。因此,主要从避免杂质的产生和痕量检测两方面进行了综述,讨论了有效控制药品中基因毒杂质限度的方法,以保证用药安全。     

梯度洗脱HPLC法测定盐酸克林霉素棕榈酸酯及制剂的有关物质

目的:建立梯度洗脱HPLC法测定盐酸克林霉素棕榈酸酯原料药、分散片、颗粒及干混悬剂的有关物质。方法:采用Agilent ZORBAX XDB-C8(4.6 mm×150 mm,5μm)柱,流动相A为5 mmol·L-1醋酸铵溶液-乙腈(50∶50),流动相B为乙腈,流速为1.0 mL·min-1,线性梯度洗脱,检测波长为230 nm。结果:盐酸克林霉素棕榈酸酯与10种中间体、副产物完全分离。重复性RSD为2.9%,检测限为10μg·mL-1。结论:方法简便、灵敏、重复性好,可用于本品的质量控制。