盐酸环丙沙星纯化中微量有机杂质的分离与结构研究

用液相色谱法检测盐酸环丙沙星原药，发现一杂质峰。该杂质经分离，确证其结构为７－氯－１－环丙基－６－（１－哌嗪基）－１，４－二氢－４－氧代喹啉－３－羧酸盐酸盐（３）。     

埃索美拉唑及其光学异构体的亲和毛细管电泳手性拆分

以牛血清白蛋白为手性添加剂,建立埃索美拉唑对映体杂质检查的亲和毛细管电泳方法,并采用荧光光谱、圆二色光谱法,通过研究埃索美拉唑及光学异构体与牛血清白蛋白作用的热力学参数、焓熵驱动过程及蛋白构象变化对其拆分机理进行探讨。建立的电泳分离条件为:未涂层石英毛细管柱(50 cm×50 μm,有效长度41.5 cm),以pH 8.0的20 mmol/L磷酸二氢钠-磷酸氢二钠缓冲液(含250 μmol/L牛血清白蛋白和7%正丙醇)作为运行缓冲液,正向运行电压30 kV,柱温25 ℃,检测波长302 nm,压力进样(5 kPa,5 s)。在优化的实验条件下,埃索美拉唑与其对映体的分离度大于1.8,对映体杂质的最低检测限和定量限分别为0.8和2.0 μg/mL,在2~20 μg/mL浓度范围内线性关系良好;平均回收率为100.4%,RSD小于2.0%。该方法可用于埃索美拉唑原料药的对映体杂质检查。     

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.     

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。     

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。     

RP-HPLC法检查莫达非尼中有关物质及其片剂的含量测定

目的；建立用RP-HPLC法进行莫达非尼有关物质及其片剂的含量测定方法。方法：采用ODS柱，以ψ（乙腈：水）=4：6）为流动相，流速1mL/min；检测波长，结果：在选定的色谱条件下，有关物质与主药分离良好，莫达非尼在1.661-4.982μg，即进样量为20μL时的样品ρ=83-249μg/mL范围内，浓度与峰面积线性良好，平均回收率100.11%,RSD=0.33%；结论：本法可用于莫达非尼有关物质的检查及片剂的含量测定。     

RP-HPLC法测定盐酸洛美沙星及其杂质的含量

采用RP－HPLC法测定盐酸洛美沙星及其杂质的含量。色谱柱：YWG－C18（4．6mm×250mm，10μm），流动相：庚磺酸钠-磷酸二氢钾溶液－甲醇－磷酸（49：51：0．7），检测波长：287um。含量测定采用外标法定量，平均回收率为98．6％（RSD=1．06％）。杂质检查用面积归一化法。     

“网脱Ⅰ号”口服液的壳聚糖絮凝除杂工艺研究

目的：探讨壳聚糖对“网脱Ⅰ号”口服液的絮凝除杂效果。方法：壳聚糖用于“网脱Ⅰ号”口服液的絮凝除杂,以澄明度、有效成分含量为指标,对壳聚糖的用量、药液浓缩比进行优选,并与醇沉工艺进行比较。结果：壳聚糖絮凝法与醇沉法同样能使药液澄清,在有效成分的保留上,前者优于后者。结论：壳聚糖絮凝法可用于“网脱Ⅰ号”口服液的絮凝除杂工艺。     

Characterization of a novel impurity in bulk drug eprosartan by ESI/MS and NMR

A simple and sensitive liquid chromatography tandem multi-stage mass spectrometry (HPLC/MSⁿ) method suitable for eprosartan analysis was developed, by which an unknown impurity in bulk drug eprosartan was detected. The fragmentation behavior of eprosartan and the impurity in negative mode was investigated. Two molecules of CO₂ lost from eprosartan precursor ion were observed, while four molecules of CO₂ were extruded from the deprotonated molecular ion to the MS³ product ions of the impurity. Furthermore, a characteristic fragmentation ion at m/z 335 was observed in both eprosartan and the impurity indicated that the impurity might have two eprosartan units. The unknown impurity was initially proposed to be eprosartan dimer connected via methylene unit at the thiophene moiety on the basis of the multi-stage mass spectrometric and exact mass evidences, and it was finally elucidated as 4,4′-(5,5′-(1E,1′E)-3,3′-(4,4′-methylenebis(thiophene-4,2-diyl))bis(2-carboxyprop-1-ene-3,1-diyl)bis(2-butyl-1H-imidazole-5,1-diyl))bis(methylene) dibenzoic acid by NMR experiments including 1D (¹H NMR, ¹³C NMR, DEPT135⁰) and 2D (¹H-¹HCOSY, HMQC and HMBC) data.     

Structural elucidation of the Rifaximin Ph. Eur. Impurity H

Rifaximin, a semisynthetic, rifamycin-based non-systemic antibiotic is used in the treatment of acute and chronic gastrointestinal disorders. The aim of this study was the elucidation of the molecular structure of the 802 Dalton impurity which was found in Rifaximin industrial batches and reported with an erroneous structure in European Pharmacopoeia 6.5 (2009) [7] monograph as Rifaximin Impurity H. This impurity was isolated from Rifaximin by preparative HPLC and purified by column chromatography. The molecular structure was evidenced by means of ¹H and ¹³C NMR spectroscopy, mass spectrometry and FT-IR.