Quantification of Structurally Alert Mutagenic Impurities in Meropenem Trihydrate Drug Substance by Liquid Chromatography with High Resolution Mass Spectrometer (LC-HRMS)

Potential mutagenic impurities in Active Pharmaceutical Ingredient, Meropenem Trihydrate were assessed and a novel analytical method for their quantification was developed and validated. This Liquid Chromatographic method using High Resolution Mass Spectrometer (LC-HRMS) technique is proved to be suitable for simultaneous quantification of all ten identified impurities with required specificity, sensitivity, resolution, precision, accuracy, and other method characteristics as per ICH Guidelines. The acceptable limit of less than 2.9 μg/g was considered for evaluations, based on drug substance dosage and duration of treatment. The method stands most sensitive with a Limit of Detection of 0.35 μg/g, considering the challenge full acceptance criteria as per current regulatory standards.

晶体zinc 1-malate trihydrate∶Cu^(2+)的自旋哈密顿参量及局部结构的理论研究

在晶体场理论的基础上,利用四角对称3d9离子自旋哈密顿参量高阶微扰公式计算了Zinc 1-malate trihydrate:Cu2+的g因子(g//,g⊥)和超精细结构常数(A//,A⊥)。结果表明,由于Jahn-Teller效应,Zinc 1-malate trihydrate:Cu2+晶体中配体氧八面体沿C4轴方向伸长约0.0033 nm,络离子[CuO6]10-的键长R//≈0.2157 nm,R⊥≈0.2058 nm;局域结构沿C4轴方向呈伸长八面体结构。所得EPR参量理论计算与实验符合较好,并对上述结果进行了讨论。

Variation of soda content in fine alumina trihydrate by seeded precipitation

High soda content in fine alumina trihydrate（ATH） limits its application and increases the soda consumption. The variation of soda content in the fine ATH by seeded precipitation was determined by detection of electric conductivity of solution, soda content in ATH, measurement of particle size distribution and microscopic analysis. The results show that high concentration of sodium aluminate solution, ground circulative seed, low temperature or fast initial precipitation rate increases the soda content in ATH. Soda mainly exists in lattice soda and less soda in desilication product （DSP） exists in the fine ATH precipitated from sodium aluminate solution with concentration of Al2O3 （ρAl2O3） more than 160 g/L and mass ratio of alumina to silica （μSiO2） of 400, and lattice soda decreases with increasing initial precipitation temperature, aging seed, and low precipitation rate and precipitation time. Results also imply that -＋ 4）Na Al（OH ion-pair influences lattice soda content in ATH on the basis of electric conductivity variation.

Surface properties of superfine alumina trihydrate after surface modification with stearic acid

The surface properties of superfine alumina trihydrate （ATH） after surface modification were studied by measuring the contact angle, active ratio, oil adsorption, total organic carbon, adsorption ratio, and Fourier transform infrared （FTIR） spectrum. The contact angle increased initially and then slowly decreased with an increase of the amount of stearic acid. However, the surface flee energy decreased ini- tially and then increased. Surface modification with stearic acid or sodium stearate can benefit from elevating temperature. The base surface tension component and the free energy of Lewis acid-base both declined sharply following the surface modification. Excess stearic acid was physically adsorbed in the form of multilayer adsorption, and an interaction between oxygen on the ATH surface and hydroxyl in stearic acid was subsequently determined. Our results further indicated that the contact angle and adsorption ratio can be used as control indicators for surface modification compared with active ratio, oil adsorption and total organic carbon.

Measurement and correlation of solubility of meropenem trihydrate in binary(water＋acetone/tetrahydrofuran) solvent mixtures

The solubility of meropenem trihydrate in water+acetone mixtures and water+tetrahydrofuran mixtures were determined from T=(278.15 to 303.15) K by static method under atmospheric pressure.Effects of solvent composition and temperature on solubility of meropenem trihydrate were discussed.To extend the applicability of the solubility data,experimental solubility data in two kinds of binary solvent mixtures were correlated by the Apelblat equation and NIBS/Redlich–Kister model.It was found that the two models could satisfactorily correlate the experimental data and the Apelblat equation could give better correlation results.

Interaction of cetyltrimethylammonium bromide with cefixime trihydrate drug at different temperatures and compositions: Effect of different electrolytes

Herein,conductivity measurements have been carried out to explore the interaction between cetyltrimethylammonium bromide(CTAB,a cationic surfactant) and antibiotic drug(cefixime trihydrate(CMT)) in water and also in occurrence of inorganic salts(NaCl,Na2 SO4 and Na3 PO4) over the temperature range of 303.15-323.15 K with an interval of 5 K.In all cases,two critical micelle concentrations(c^*) were achieved for the CMT-surfactant system.Addition of CMT drug to CTAB solution decreases the values of c^* which indicates the interaction between CMT and CTAB.Both values of c^* for CMT-CTAB mixture in the presence of salts are lower in magnitude compared to the aqueous medium which indicates that micellization of the CMT-CTAB mixed system is favorable in salt solution.The values of △Gm^0 were obtained to be negative indicating the spontaneity of the micellization process and the extent of spontaneity further increases by means of rising temperature.The obtained outcomes from the ΔHm^0 and ΔSm^0 values disclose that the interactions between CMT and CTAB are mostly electrostatic along with hydrophobic in nature.The thermodynamic parameters of transfer and enthalpy-entropy compensation phenomenon were also determined and discussed in detail.

Effect of concentration of ATH on mechanical properties of polypropylene/aluminium trihydrate(PP/ATH) composite

Aluminium trihydrate(ATH) is being extensively added to polypropylene(PP) to make a fire retardant composite. Blends of PP/ATH composite are more fire resistant as compared to pure PP. Percentage proportion of both the constituents in the final composite depends upon the application. Improvement in the fire retardant properties of such composites have been studied and published in literature but effects on mechanical strength have not been addressed. The effect of concentration of ATH on the strength of PP/ATH composite was presented. The tensile, flexural and fracture properties were studied and discussed. Experimental tests, ASTM analytical formulae and finite element approach were used. It has been found that increase in ATH has an inverse effect on the mechanical strength.

Optimization and Characterization of Nano Aluminum Trihydrate-Based Flame-Retardant Materials in the Rotating Packed Bed Reactor

A CO2/NaAlO2/H2O absorption-reaction system was adopted to prepare nano aluminum trihydrate (ATH) particles for cables use in a rotating packed-bed (RPB) reactor (Phase I). The Taguchi experimental design was used to give an orthogonal array, L9(34). The parameters were the speed of rotation (A), gas-liquid flow rate ratio (B), aging temperature (C) and aging time (D), each having three levels. According to the signal/noise (S/N) ratio analysis, optimum condition for BET area (Sw) was found to be A3B3C1D1, while the parameter significance was DABC. Empirical formula for Sw was also obtained and discussed. Subsequently, the optimum size (10.7 nm) of ATH powders was used to blend with the matrix including plastics and additives (Phase II) for characterization further. The examination of composite materials showed that the limiting oxygen index (LOI) was higher than 28, indicating an excellent fire-retarding property. The results also showed that the LOI for nano ATH is higher than that bought from the market, while the fire-retarding grade examination (UL-94 test) for both ATHs was found to be of a V-0 grade. In addition, the mechanical properties for nano ATH were measured prior to using the ATH from the market.

Revealing the specific role of sulfide and nano-alumina in composite solid-state electrolytes for performance-reinforced ether-nitrile copolymers

Composite solid-state electrolytes represent a critical pathway that balances the interface compatibility and lithium-ion conductivity in all-solid-state batteries.The quest for stable and highly ion-conductive combinations between polymers and fillers is vital,but blind attempts are often made due to a lack of understanding of the mechanisms involved in the interaction between polymers and fillers.Herein,we employ in-situ polymerization to prepare a polymer based on an ether-nitrile copolymer with high cathode stability as the foundation and discuss the performance enhancement mechanisms of argyrodite and nano-alumina.With 1%content of sulfide interacting with the polymer at the two-phase interface,the local enhancement of lithium-ion migration capability can be achieved,avoiding the reduction in capacity due to the low ion conductivity of the passivation layer during cycling.The capacity retention after 50cycles at 0.5 C increases from 83.5%to 94.4%.Nano-alumina,through anchoring the anions and interface inhibition functions,eventually poses an initial discharge capacity of 136.8 m A h g^(-1)at 0.5 C and extends the cycling time to 1000 h without short-circuiting in lithium metal batteries.Through the combined action of dual fillers on the composite solid-state electrolyte,promising insights are provided for future material design.

A General Procedure for Surface Modification of Nano-alumina and Its Application to Dendrimers

A general procedure for surface modification of nano-alumina using N, N＇-dicyclohexyl- carbodiimide （DCC） mediated amidation is reported. Aliphatic and aromatic carboxylic acids reacted smoothly with nano-alumina pretreated with 3-aminopropyltriethoxysilane in the presence of DCC, giving modified aluminas having organic surfaces. The grafted aluminas have been characterized qualitatively by FT-IR or ^13C CPMAS NMR spectroscopy, and quantitatively by thermogravimetric analysis and elemental analysis. The procedure was applied to polyether dendrons bearing carboxyl groups at the focal points, giving successful grafting of dendrimers onto nano-alumina.

Improvement of the Subcooling Problem of Sodium Acetate Trihydrate by a Combination of Stirring or Internal Electric Field and Nucleating Agent

Energy storage devices are the hub of a multi-energy complementary distributed energy system.Hydrated salts are the most suitable phase change material for energy storage devices,but subcooling is the main obstacle to their application.Nucleation requires a driving force so the use of nucleating agents alone does not reduce subcooling to a very low level.To address this issue,this paper first screened nucleating agents and then further reduced the subcooling of sodium acetate trihydrate in conjunction with stirring or direct current.The effects of rotor mass,rotational speed,direct current voltage,and electrode material on nucleation were analyzed.Finally,the stability of the composite phase change material in the presence of simultaneous stirring and energization was analyzed.The results showed that the addition of 1.5%in weight of disodium hydrogen phosphate dodecahydrate to sodium acetate trihydrate can reduce the subcooling to about 2.3℃.Continued addition of stirring or electricity can reduce the subcooling of sodium acetate trihydrate to within 0.5℃ or even eliminate it.The higher the momentum of the stirring,the better the improvement in subcooling,phase separation,and thermal conductivity.The higher the direct current voltage,the better the nucleation effect,but the electrode life will be lower.The silver electrode has the best nucleation effect.No new material was produced in the solution after 100 cycles in the presence of both stirring and direct current.The melting point of the phase change material was increased by 0.2℃ and the latent heat value decreased by 1.8%,still with good stability.The trace of deionized water should be added to the phase change material in subsequent studies to compensate for the consumption ofwaterby theanodicelution.

Thermal Property Enhancement of a Novel Shape-Stabilized Sodium Acetate Trihydrate-Acetamide/Expanded Graphite-Based Composite Phase Change Material

Phase change materials(PCMs)are a kind of highly efficient thermal storage materials which have a bright application prospect in many fields such as energy conservation in buildings,waste heat recovery,battery thermal management and so on.Especially inorganic hydrated salt PCMs have received increasing attention from researchers due to their advantages of being inexpensive and non-flammable.However,inorganic hydrated salt PCMs are still limited by the aspects of inappropriate phase change temperature,liquid phase leakage,large supercooling and severe phase separation in the application process.In this work,sodium acetate trihydrate was selected as the basic inorganic PCM,and a novel shape-stabilized composite phase change material(CPCM)with good thermal properties was prepared by adding various functional additives.At first,the sodium acetate trihydrate-acetamide binary mixture was prepared and the melting point was adjusted using acetamide.Then the binary mixture was incorporated into expanded graphite to synthesize a novel shape-stabilized CPCM.The thermophysical properties of the resultant shape-stabilized CPCM were systematically investigated.The microscopic morphology and chemical structure of the obtained shape-stabilized CPCM were characterized and analyzed.The experiment results pointed out that acetamide could effectively lower the melting point of sodium acetate trihydrate.The obtained shape-stabilized CPCM modified with additional 18%(mass fraction)acetamide and 12%(mass fraction)expanded graphite exhibited good shape stability and thermophysical characteristics:a low supercooling degree of 1.75℃and an appropriate melting temperature of 40.77℃were obtained;the latent heat of 151.64 kJ/kg and thermal conductivity of 1.411 W/(m·K)were also satisfactory.Moreover,after 50accelerated melting-freezing cycles,the obtained shape-stabilized CPCM represented good thermal reliability.

高铁低硫型铝土矿的工艺矿物学研究

铝土矿主要由铝的氢氧化物、氧化物和硅酸盐矿物组成,是生产金属铝的主要原料。以某高铁低硫型铝土矿为研究对象,采用元素分析、X射线衍射和扫描电镜等方法,研究铝土矿的化学组成、主要矿物的嵌布关系、矿物表面形貌等。结果表明,矿石中Al_(2)O_(3)含量为44.22%,SiO_(2)含量为5.71%,二者的比值约为7.74。矿石中主要矿物为三水铝石,褐铁矿(水针铁矿)和勃姆石含量较少。它既含有少量石英、高岭石、绿泥石和钛铁矿,又含有微量钠长石、方解石、磷灰石、一水硬铝石、铁素体和金红石等。褐铁矿中分散有微量铝,大多数褐铁矿和石英以极细粒夹杂物的形式包裹在铝矿物集合体中。矿物粒度分析表明,铝矿物集合体嵌布粒度不小于0.074 mm的累计含量为92.50%,较集中于0.015~0.060 mm,嵌布粒度小于0.010 mm的含量为0.5%;铁矿物集合体嵌布粒度不小于0.074 mm的累计含量为34.45%,嵌布粒度小于0.010 mm的含量较高,为43.44%;石英嵌布粒度不小于0.074 mm的累计含量为40.15%,嵌布粒度小于0.010 mm的含量较高,为39.86%。矿石中的大部分铝以独立矿物的形式存在。

超声波对三水醋酸钠相分离及结晶的影响

The effects of ultrasonic radiation on phase separation as well as the crystallization of sodium acetate trihydrate,a typical salt hydrate phase change material(PCM),were studied experimentally.It is shown that ultrasonic radiation may inhibit phase separation to a certain degree.The influence of ultrasonic radiation on crystallization is also found.The addition of PCM grain can inhibit supercooling effectively.The crystallization is related to the supercooling degree.Furthermore,the effects of ultrasonic radiation on inhibiting phase separation of salt hydrates are discussed based on theoretical analysis.

氢氧化铝阻燃剂的表面改性

为改善氢氧化铝阻燃剂与聚合物间的相容性,对氢氧化铝进行了改性研究,确定了量佳工艺条件,并对改性后的氢氧化铝粉体进行了性能测试。结果表明,最佳改性剂为硬脂酸,改性剂的量佳用量为1.5%。改性后的氢氧化铝粉体的表面性质发生了明显变化,沉降速度减慢,吸油值降低,活化指数增大,分散性好。

纳米氢氧化铝填充LDPE/EVA的力学和阻燃性能

对纳米氢氧化铝(CGATH)在低密度聚乙烯/乙烯醋酸乙烯酯共聚物体系中(lowdensitypolyethylene/ethylenevinylacetatecopolymer,简称LDPE/EVA),填充量对力学性质和阻燃性质的影响进行了研究.通过力学性能测试和SEM分析表明,随着CGATH填充量的增加,树脂体系的断裂伸长率急剧下降,而其拉伸强度则呈先下降后上升的趋势,当CGATH的填充量为60%时,其拉伸强度达12.5MPa.通过燃烧性能测试、TG和DSC分析表明,CGATH的添加能够提高树脂体系的分解温度,增加结炭率,显著提高极限氧指数.通过综合分析,得到填充量为60%时,能够达到树脂体系力学性能与燃烧性能的最佳状态.

纳米氢氧化铝阻燃剂表面改性及其在聚丙烯中的应用

对高性能阻燃剂纳米氢氧化铝进行表面改性研究 ,结果表明改性后的氢氧化铝比表面积增大、吸油值降低、分散性好 ,填充于聚丙烯后明显改善熔融现象 ,有较好的阻燃效果 ,且材料的力学性能有所提高。

三水合乙酸钠在相变单元的传热特性及其过冷度改善

以三水合乙酸钠（CH3COONa·3H2O）为储热基料,研究了改善其过冷度的几种措施——添加剂、振动法、搅拌法对于其成核过程的影响。以不锈钢单元体模拟日常生活中的蓄热器,进行融化-凝固实验。绘制步冷曲线以及DSC测试,观察其过冷度及蓄、放热特性的变化。结果发现,成核剂Na2HPO4·12H2O以及纳米成核剂SiO2分别将过冷度降至23℃以及2.5℃以下。超声振动作用使得CH3COONa·3H2O的过冷度仅为0.7℃左右。引入15min机械搅拌作用,过冷度降到了2℃以下,并且放热平台持续时间较长。超声振动和机械搅拌的作用还会有效解决CH3COONa·3H2O的相分离现象,同时也保持了较高的蓄热能力。最后,对比分析了各种成核手段的优缺点,在实际应用或者研究中应根据蓄热器的尺寸、经济性等选择合适的办法改善过冷度。

美罗培南三水合物的合成

目的合成碳青霉烯类抗生素美罗培南。方法以羟脯氨酸为起始原料,经5步反应合成得到侧链(2S ,4S) - 二甲氨基甲酰基- 4 - 巯基- 1 -(4 -硝基苯甲氧羰基)吡咯烷(Ⅴ) ,Ⅴ与(1R ,5R ,6S) - 2 - (二苯氧基磷酰氧基) 6 - [(R) - 1 羟乙基] 1 甲基碳青霉 -2 - 烯- 3 -羧酸对硝基苄酯(Ⅵ)经取代、氢化、大孔吸附树脂柱色谱纯化得到美罗培南三水合物,总收率为13 .9% (以羟脯氨酸计)。结果与结论合成了美罗培南三水合物,其结构经质谱、核磁共振氢谱和热重分析确证。

改进三水醋酸钠蓄热性能的实验研究

无机水合盐三水醋酸钠(CH3COONa.3H2O)具有58℃的熔点和较大的融解热(264 J/g),但作为相变蓄热材料有析出和过冷两大缺点,极大地影响了它的贮热容量和释热温度.在分析三水醋酸钠理化特性的基础上,实验研究了添加抗沉淀剂以及添加PCM晶粒对三水醋酸钠析出和过冷的抑制效果,对实验现象和结果进行了详细的分析研究,并对抑制机理作了分析讨论.研究结果显示增稠剂CMC具有良好的析出抑制效果,添加PCM晶粒是一种有效的过冷抑制方法.