高效液相色谱串联质谱法测定氯沙坦钾中的遗传毒性杂质N-亚硝基-N-甲基-4-氨基丁酸

目的建立了一种高效液相色谱-三重四极杆串联质谱法,对氯沙坦钾原料药中遗传毒性杂质N-亚硝基-N-甲基-4-氨基丁酸(NMBA)进行测定。方法色谱柱为岛津Shim-pack XR-ODSⅡ色谱柱(2.0 mm×150 mm,2.2μm),流动相为0.1%甲酸水溶液(A)和甲醇(B),进行梯度洗脱,流速0.3 mL·min^-1,柱温为40℃,采用ESI离子化-三重四极杆质谱多反应监测(MRM)正离子模式检测,碰撞电压分别为-11,-13和-13 V,碰撞气氩气270 kPa,NMBA的离子对分别为m/z 147.15→117.10,147.15→87.10和147.15→44.10。结果该方法中NMBA在1~100 ng·mL^-1内线性关系良好,日内和日间的保留时间和峰面积的重复性良好(RSD均小于1.10%,n=6和n=18),低、中、高3个浓度的平均回收率在94.40%~98.04%之间。结论本方法简单方便,可快速有效的对氯沙坦钾原料药中NMBA进行限度检查并实现定量分析。     

固天泉胶囊水提液除杂工艺研究

目的:探讨大孔吸附树脂法、壳聚糖澄清法和乙醇沉淀法在固天泉胶囊水提液中除杂结果。方法:比较大孔吸附树脂法、乙醇沉淀法和壳聚糖澄清法所得到的浸膏得率及浸膏中人参皂苷Rg₁,Re的定性分析以及Rg₁、阿魏酸含量测定考察。结果:乙醇沉淀法所得的浸膏得率为17.2％,壳聚糖澄清法所得的浸膏得率为12.8％,大孔吸附树脂法所得的浸膏得率为3.1％,3种方法均能够较好地使水提液澄明,且后两者还能够在降低浸膏得率、保留有效成分、保证制剂稳定性方面优于前者,并能缩短生产周期,降低成本。结论:壳聚糖澄清试剂法较适合于固天泉胶囊水提液除杂工艺。     

褶合光谱法用于盐酸普鲁卡因注射液中对氨基苯甲酸的限量检测

 目的:建立用褶合光谱法进行盐酸普鲁卡因注射液中对氨基苯甲酸(PABA)限量检测的方法。方法:选择褶合光谱波长范围为210～330 nm，间隔4 nm,以限量杂质三维褶合光谱差谱点域值为判据。结果:检测了5批样品，结果与中国药典规定的方法一致。结论:方法简便、灵敏、结果准确，适用于药物的杂质限量检测。     

HPLC法测定盐酸麻黄碱和盐酸伪麻黄碱中杂质

目的建立盐酸麻黄碱(E)和盐酸伪麻黄碱(PE)中杂质的高效液相色谱HPLC测定方法。方法用RPC18色谱柱,以20mmol/LKH2PO4水溶液-甲醇(96∶4)为流动相,检测波长为210nm,分析时间为20min。结果6种麻黄生物碱均达到基线分离;混合对照品连续进样6次,色谱峰面积RSD均小于1.0%;对照品质量浓度在选定范围内呈现良好的线性关系(R2>0.999);各成分最低检出限分别为:去甲基麻黄碱(NE)为0.05μg/mL,去甲基伪麻黄碱(NPE)为0.04μg/mL,E和PE为0.1μg/mL,甲基麻黄碱(ME)和甲基伪麻黄碱(MPE)为0.2μg/mL;各成分的加样回收率均大于97.1%;6个待测样品均被检测出不同程度的杂质。结论本方法分离度好、精密度高、专属性强、灵敏度高,可用于麻黄生物碱类药物中杂质成分的定性和定量测定。     

利用LC-MS/MS法快速鉴定盐酸头孢吡肟中的同分异构体杂质

目的建立应用LC-MS/MS技术快速鉴定盐酸头孢吡肟原料药中的同分异构体杂质的方法。方法以乙腈-10 mmol·L^-1乙酸铵(5∶95)为流动相经C₁₈柱分离,通过电喷雾串联质谱在线检测，获得相关的色谱和质谱信息。结果在所建立的条件下，盐酸头孢吡肟及其同分异构体杂质获得有效分离，主成分和其同分异构体杂质的保留时间分别为15.28 min和9.18 min，同时它们的二级质谱产物离子信息及其裂解方式呈现明显的差异。结论本法能快速、准确地分离鉴定盐酸头孢吡肟原料药中的同分异构体杂质，从而可以对其原料药进行质量控制。     

那格列奈及其片剂中L-异构体的HPLC测定

建立了HPLC法测定那格列奈及其片剂中的杂质L-异构体的含量.采用以α-酸性糖蛋白键合硅胶为固定相的手性色谱柱,0.02mol/L磷酸钾缓冲液(pH 7.1)-乙腈(98:2)为流动相,检测波长210nm,L-异构体检测限为2ng,平均回收率为98.0%.     

Micrograin Superplasticity: Characteristics and Utilization

Micrograin Superplasticity refers to the ability of fine-grained materials (1 µm < d < 10 μm, where d is the grain size) to exhibit extensive neck-free elongations during deformation at elevated temperatures. Over the past three decades, good progress has been made in rationalizing this phenomenon. The present paper provides a brief review on this progress in several areas that have been related to: (a) the mechanical characteristics of micrograin superplasticity and their origin; (b) the effect of impurity content and type on deformation behavior, boundary sliding, and cavitation during superplastic deformation; (c) the formation of cavity stringers; (d) dislocation activities and role during superplastic flow; and (e) the utilization of superplasticity.     

HPLC测定(S)-4-苯基-2-噁唑烷酮的纯度

目的采用HPLC法测定(S)-4-苯基-2-噁唑烷酮(SPO)的纯度。方法采用Welchrom C18色谱柱,流动相为0.02 mol·L-1磷酸二氢钾(KOH调p H5)-乙腈(60∶40),检测波长210 nm,流速1.0 m L·min-1,柱温35℃。结果 SPO0.3036~6.072μg·m L-1与峰面积的线性关系良好(r=0.9999),检测限和定量限分别为0.9099、3.033 ng。结论所用方法准确、灵敏、快速,适用于检测SPO中的微量杂质。     

Profiling of synthesis‐related impurities of the synthetic cannabinoid Cumyl‐5F‐PINACA in seized samples of e‐liquids via multivariate analysis of UHPLC−MSn data

Vaping of synthetic cannabinoids via e‐cigarettes is growing in popularity. In the present study, we tentatively identified 12 by‐products found in a pure sample of the synthetic cannabinoid Cumyl‐5F‐PINACA (1‐(5‐fluoropentyl)‐N‐(2‐phenylpropan‐2‐yl)‐1H‐indazole‐3‐carboxamide), a prevalent new psychoactive substance (NPS) in e‐liquids, via high‐resolution mass spectrometry fragmentation experiments (HRMS/MS). Furthermore, we developed a procedure to reproducibly extract this synthetic cannabinoid and related by‐products from an e‐liquid matrix via chloroform and water. The extracts were submitted to flash chromatography (F‐LC) to isolate the by‐products from the main component. The chromatographic impurity signature was subsequently assessed by ultra‐high‐performance liquid chromatography coupled to mass spectrometry (UHPLC–MS) and evaluated by automated integration. The complete sample preparation sequence (F‐LC + UHPLC–MS) was validated by comparing the semi‐quantitative signal integrals of the chromatographic impurity signatures of five self‐made e‐liquids with varying concentrations of Cumyl‐5F‐PINACA [0.1, 0.2, 0.5, 0.7 and 1.0% (w/w)], giving an average relative standard deviation of 6.2% for triplicate measurements of preparations of the same concentration and 10.5% between the measurements of the five preparations with different concentrations. Lastly, the chromatographic signatures of 14 e‐liquid samples containing Cumyl‐5F‐PINACA from police seizures and Internet test purchases were evaluated via hierarchical cluster analysis for potential links. For the e‐liquid samples originating from test purchases, it was found that the date of purchase, the identity of the online shop, and the brand name are the critical factors for clustering of samples.     

探讨定量构效关系模型在药物及其杂质毒性预测方面的应用

随着定量构效关系（QSAR）模型从二维至多维的不断发展,它被越来越广泛地应用于各个领域,同时也为药品的监管提供了新的参考方案。QSAR模型对于杂质的毒性预测可应用于药品的研发和质量控制过程,有利于控制药品的安全风险,缩减企业的研发成本。QSAR模型的应用程序也在不断优化,以确保QSAR模型可以不断地适用于新药及未知杂质的毒性研究。本文从QSAR模型的建模基础及发展历程出发,对近年来该模型在药物及其杂质毒性预测方面的应用研究报道进行了归纳总结。