Process Steps for High Quality Si-Based Epitaxial Growth at Low Temperature via RPCVD

The key process steps for growing high-quality Si-based epitaxial films via reduced pressure chemical vapor deposition (RPCVD) are investigated herein. The quality of the epitaxial films is largely affected by the following steps in the epitaxy process: ex-situ cleaning, in-situ bake, and loading conditions such as the temperature and gaseous environment. With respect to ex-situ cleaning, dry cleaning is found to be more effective than wet cleaning in 1:200 dilute hydrofluoric acid (DHF), while wet cleaning in 1:30 DHF is the least effective. However, the best results of all are obtained via a combination of wet and dry cleaning. With respect to in-situ hydrogen bake in the presence of H₂ gas, the level of impurities is gradually decreased as the temperature increases from 700 °C to a maximum of 850 °C, at which no peaks of O and F are observed. Further, the addition of a hydrogen chloride (HCl) bake step after the H₂ bake results in effective in-situ bake even at temperatures as low as 700 °C. In addition, the effects of temperature and environment (vacuum or gas) at the time of loading the wafers into the process chamber are compared. Better quality epitaxial films are obtained when the samples are loaded into the process chamber at low temperature in a gaseous environment. These results indicate that the epitaxial conditions must be carefully tuned and controlled in order to achieve high-quality epitaxial growth.     

GC-MS/MS测定替米沙坦片中10种亚硝胺类基因毒性杂质

目的 建立GC-MS/MS同时测定替米沙坦片中N-亚硝基二甲胺(NDMA)、N-亚硝基甲乙胺(NMEA)、N-亚硝基二乙胺(NDEA)、N-亚硝基-N-乙基异丙胺(NEIPA)、N-亚硝基二异丙胺(NDIPA)、N-亚硝基二正丙胺(NDPA)、N-亚硝基二正丁胺(NDBA)、N-亚硝基哌啶(NPIP)、N-亚硝基吡咯烷(NPYR)和N-亚硝基吗啉(NMOR)10种亚硝胺类基因毒性杂质的含量。方法 样品经甲醇提取,经Agilent VF-WAXms(30 m×0.25 mm,1 μm)毛细管气相色谱柱分离,采用多反应离子监测(MRM)模式进行定量分析。结果 NDMA、NMEA、NDEA、NEIPA、NDIPA、NDPA、NDBA和NPIP在0.2~50 ng·mL^-1线性关系良好,相关系数均为1.000 0;检测限均为0.05 ng·mL^-1,定量限均为0.2 ng·mL^-1,平均回收率分别为103%(RSD=9.2%,n=9),108%(RSD=6.1%,n=9),107%(RSD=5.3%,n=9),106%(RSD=3.9%,n=9),102%(RSD=5.0%,n=9),99%(RSD=6.9%,n=9),97%(RSD=8.6%,n=9),101%(RSD=4.4%,n=9)。NPYR和NMOR在1.0~50 ng·mL^-1内线性关系良好,相关系数均为1.000 0;检测限均为0.4 ng·mL^-1,定量限均为1.0 ng·mL^-1,平均回收率分别为95%(RSD=6.4%,n=9),103%(RSD=6.1%,n=9)。所收集的254批样品中,12批次检出NDMA,其余9个杂质在254批样品中均未检出。结论 该方法操作简便、灵敏度高,专属性强,适用于替米沙坦片或其他制剂中NDMA、NMEA、NDEA、NEIPA、NDIPA、NDPA、NDBA、NPIP、NPYR和NMOR 10种基因毒性杂质的检测。     

尼莫地平口服溶液中降解杂质的结构鉴定及分析

目的 对尼莫地平口服溶液中2个未知降解杂质进行结构鉴定和分析测试。方法 通过二维液相色谱-高分辨质谱（2DLC-HRMS）推测未知杂质的化学结构,并采用定向合成的方式获得杂质单体,经核磁共振¹H-NMR、¹³C-NMR对杂质结构进行确证,采用Thermo Syncronis C₁₈（250 mm×4.6 mm,5 μm）色谱柱,以5 mmol·L^-1磷酸二氢钾（pH 2.8）为流动相A,以甲醇-乙腈（50∶50）为流动相B,梯度洗脱;流速为1.0 mL·min^-1;柱温为30℃;检测波长为235 nm。结果 尼莫地平与其降解杂质分离良好,各杂质校正因子均在0.9~1.1。结论 建立的方法专属性好,可有效分离和测定尼莫地平口服溶液中的有关物质。本研究可为尼莫地平口服溶液及其他剂型的杂质控制提供参考。     

HPLC-Q-TOF-MS/MS分析盐酸小檗碱的杂质谱

目的 采用高效液相色谱串联四级杆飞行时间质谱(HPLC-Q-TOF-MS/MS)联用技术对盐酸小檗碱杂质谱进行结构鉴定。方法 采用Agilent ZORBAX SB-C₁₈(4.6 mm×250 mm,5 μm),10 mmol·L^-1乙酸铵溶液(冰醋酸调节pH至3.0)-乙腈(75:25)为流动相,流速为0.8 mL·min^-1,紫外检测波长为345 nm,对小檗碱原料进行杂质分离。再采用HPLC-Q-TOF-MS/MS测定小檗碱及其杂质一级精确分子量及二级碎片离子,并进行结构解析。结果 小檗碱与其杂质分离良好,植物提取原料中存在7个杂质,化学合成原料中存在5个杂质。结论 液质联用技术能有效地鉴定小檗碱及其杂质结构,为质量控制提供了参考依据。     

中心切割二维液相色谱-质谱法定性鉴别盐酸特比萘芬乳膏中的未知杂质及其校正因子的测定

目的 采用中心切割在线二维液相色谱四级杆飞行时间质谱法定性鉴别盐酸特比萘芬乳膏中相对保留时间（relative retention time,RRT）0.4的杂质并对其校正因子进行测定。方法 一维液相色谱采用Diamonsil C₁₈色谱柱,以三乙胺缓冲液（0.2%三乙胺溶液,用冰醋酸调节pH值至7.5）-甲醇-乙腈（30∶42∶28）为流动相A,以三乙胺缓冲液-甲醇-乙腈（5∶57∶38）为流动相B,梯度洗脱,流速为0.8 mL·min^-1,检测波长为280 nm;二维液相色谱采用Tsk gel ODS 100 V色谱柱,以0.1%甲酸水溶液-甲醇（20∶80）为流动相;质谱采用大气压化学电离离子源（APCI）,正离子模式检测。根据一维液相色谱条件,对该杂质的校正因子进行测定。结果 根据质谱定性结果并结合对照品比对,确认盐酸特比萘芬乳膏中RRT 0.4的杂质为工艺杂质,可为后续精制工艺的改进提供依据。该杂质相对于特比萘芬的校正因子为0.21,提示定量时选择加校正因子的主成分自身对照法较为合理。结论 研究建立的中心切割在线二维液相色谱质谱法可用于盐酸特比萘芬乳膏中弱极性杂质的在线定性鉴别,为特比萘芬中其他弱极性杂质的鉴定提供了研究思路,也为复杂基质样品中微量杂质的分析鉴别提供了思路,可以为更好地监测盐酸特比萘芬乳膏的质量提供技术借鉴。     

磷酸奥司他韦干混悬剂中杂质谱解析及辅料降解杂质分析

目的 对磷酸奥司他韦干混悬剂中一个未知杂质进行结构鉴定、合成和分析,作为已知杂质控制。方法 通过二维液相色谱-质谱（2D-LC-MS/MS）推导未知杂质的结构,根据产品的处方工艺确定杂质来源,并采用定向合成的方式获得杂质单体。采用2D-LC-MS/MS、核磁共振、红外、紫外、热重分析等技术确证杂质的结构,最后采用HPLC对杂质进行分析方法验证。结果 确证该杂质为奥司他韦与辅料山梨醇反应生成的,杂质与奥司他韦的校正因子为1.5。结论 将该杂质命名为杂质I,作为已知杂质定入标准控制,按照自身对照加校正因子法计算杂质含量。     

Effect of Growth Temperature and Atmosphere Exposure Time on Impurity Incorporation in Sputtered Mg,Al, and Ca Thin Films

Impurities can be incorporated during thin film deposition, but also can originate from atmosphere exposure. As impurities can strongly affect the composition—structure—property relations in magnetron sputter deposited thin films, it is important to distinguish between both incorporation channels. Therefore, the impurity incorporation by atmosphere exposure into sputtered Mg, Al, and Ca thin films is systematically studied by a variation of the deposition temperatures and atmosphere exposure times. Deposition temperature variation results in morphological modifications explained by considering surface and bulk diffusion as well as grain boundary motion and evaporation. The film morphologies exhibiting the lowest oxygen concentrations, as measured by energy dispersive X-ray spectroscopy, are obtained at a homologous temperature of 0.4 for both Mg and Al thin films. For Ca, preventing atmosphere exposure is essential to hinder impurity incorporation: By comparing the impurity concentration in Al-capped and uncapped thin films, it is demonstrated that Ca thin films are locally protected by Al-capping, while Mg (and Al) form native passivation layers. Furthermore, it can be learned that the capping (or self-passivation) efficiency in terms of hindering further oxidation of the films in atmosphere is strongly dependent on the underlying morphology, which in turn is defined by the growth temperature.     

奥氮平原料药中相关杂质的合成及结构鉴定

目的合成奥氮平原料药中的相关杂质并进行结构鉴定。方法分别以奥氮平的合成中间体4-氨基-2-甲基-10H-噻吩并[2,3-b][1,5]苯二氮杂艹卓盐酸盐和奥氮平为起始原料合成奥氮平的3个相关杂质:2-甲基-10H-噻吩并[2,3-b][1,5]苯二氮杂艹卓-4-(5H)-酮(1)、1-氯甲基-1-甲基-4-(2-甲基-10H-苯并[b]噻吩并[2,3-e][1,4]二氮杂艹卓-4-哌嗪基)-1-氯化物(2)和2-甲基-4-(4-甲基-1-哌嗪基)-10H-苯并[b]噻吩并[2,3-e][1,4]二氮杂艹卓4’-N-氧化物(3)。结果与结论合成并鉴定了奥氮平质量标准中提及的3种杂质,其结构经1H-NMR、13C-NMR谱及高分辨质谱确证;并且探讨了3种杂质可能的产生途径,以期为奥氮平的质量研究和相关杂质的控制提供帮助。     

Impact of A-Site Cation Deficiency on Charge Transport in La0.5−xSr0.5FeO3−δ

The electrical conductivity of La_0.5−xSr_0.5FeO_3−δ, investigated as a function of the nominal cation deficiency in the A-sublattice, x, varying from 0 to 0.02, has demonstrated a nonlinear dependence. An increase in the x value from 0 to 0.01 resulted in a considerable increase in electrical conductivity, which was shown to be attributed mainly to an increase in the mobility of the charge carriers. A combined analysis of the defect equilibrium and the charge transport in La_0.5−xSr_0.5FeO_3−δ revealed the increase in the mobility of oxygen ions, electrons, and holes by factors of ~1.5, 1.3, and 1.7, respectively. The observed effect is assumed to be conditioned by a variation in the oxide structure under the action of the cationic vacancy formation. It was found that the cation deficiency limit in La_0.5−xSr_0.5FeO_3−δ did not exceed 0.01. A small overstep of this limit was shown to result in the formation of (Sr,La)Fe₁₂O₁₉ impurity, which even in undetectable amounts reduced the conductivity of the material. The presence of (Sr,La)Fe₁₂O₁₉ impurity was revealed by X-ray diffraction on the ceramic surface after heat treatment at 1300 °C. It is most likely that the formation of traces of the liquid phase under these conditions is responsible for the impurity migration to the ceramic surface. The introduction of a cation deficiency of 0.01 into the A-sublattice of La_0.5−xSr_0.5FeO_3−δ can be recommended as an effective means to enhance both the oxygen ion and the electron conductivity and improve ceramic sinterability.     

高效液相色谱法分析卡贝缩宫素及其有关杂质

目的:应用反相高效液相色谱法分析卡贝缩宫素及其有关杂质,并对有关杂质进行定位。方法:用 Lichrospher(?) 100 RP-C_(18)(125 mm×4 mm,5μm)色谱柱,流动相为磷酸盐缓冲液(pH 7.0)-乙腈(76:24);流速为1.2 mL·min~(-1);柱温为60℃,检测波长为220 nm。结果:卡贝缩宫素在0.25～8.0μg范围内呈良好的线性关系,r=1.000,最低检测限为2 ng,平均回收率为99.3%,各有关杂质的相对保留时间范围为相对保留时间±0.02。结论:本法简便、准确,适用于卡贝缩宫素的定量及其有关杂质的鉴别。