Identification,isolation and characterization of process-related impurities in Rizatriptan benzoate

Three process-related impurities were observed in routine monitoring of the samples by HPLC. These impurities were identified by LC–MS. One of the impurities, Imp-3 [rizatriptan-2,5-dimer] was reported in literature. Other two impurities were isolated by preparative HPLC and characterized by NMR, Mass and IR. Pure impurities obtained by isolation were co-injected with Rizatriptan benzoate sample to confirm the retention times in HPLC. Structure elucidation of these impurities by spectral data has been discussed in detail. These impurities were identified as 4-(5-((1H-1,2,4-triazol-1-yl)methyl)-3-(2-(dimethylamino)ethyl)-1H-indol-1-yl)-4-(5-((1H-1,2,4-triazol-1-yl)methyl)-3-(2-(dimethylamino)ethyl)-1H-indol-2-yl)-N,N-dimethylbutan-1-amine [rizatriptan-1,2-dimer] and [4,4-bis-(5-((1H-1,2,4-triazol-1-yl)methyl)-3-(2-(dimethylamino)-ethyl)-1H-indol-2-yl)-N,N-dimethylbutan-1-amine [rizatriptan-2,2-dimer].     

Evaluation of supercritical fluid technology as preparative technique of benzocaine-cyclodextrin complexes--comparison with conventional methods

The objective of this study was to investigate the effect of the preparation method on the physico-chemical properties of complexes prepared between beta-cyclodextrin (beta-Cyd) and benzocaine (BZC). In particular, the effectiveness of a new technique based on supercritical carbon dioxide (SC CO(2)) for preparing solid drug-cyclodextrin complexes was investigated and compared to other more conventional methods such as kneading (KN), co-evaporation (COE), co-grinding (GR) and sealed-heating (S.H.). Effects of temperature, pressure and exposure time on the properties of complexes prepared by SC CO(2) technology were also studied. The different systems were characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometry (PXRD) and dissolution test according to the dispersed amount method. The co-grinding (GR) method resulted in amorphous products while other methods led to crystalline or partially amorphous products depending on both the method and its experimental conditions. SC CO(2) method revealed to be an effective technique for preparing solid systems between beta-cyclodextrin and benzocaine, avoiding the use of organic solvents (and problems of their complete removal) and allowing an easy scale-up of the process. As for the influence of the experimental conditions in promoting the solid-state drug-carrier interaction when using the SC CO(2) method, temperature seemed to play the major role, whereas pressure and exposure times had more limited effects. Dissolution tests confirmed a limited but favourable effect in increasing the exposure time, while indicated a possible interaction effect between temperature and pressure in influencing the dissolution performance of the final product. The best product obtained by the SC CO(2) method showed dissolution properties similar to those of the co-ground product and only slightly lower than the system obtained by sealed-heating, which was the most effective technique.     

Isolation and characterization of degradation impurities in docetaxel drug substance and its formulation

The degradation of docetaxel drug substance and its injection formulation has been investigated. The majority of impurities were observed in a base degradation study and all five degradation products were characterized. These impurities were isolated, enriched and were subjected to mass and NMR spectral studies. Based on the spectral data, these were characterized as 10-deacetyl baccatin III, 7-epi-10-deacetyl baccatin III, 7-epi-10-oxo-10-deacetyl baccatin III, 7-epi docetaxel and 7-epi-10-oxo-docetaxel, respectively. The last two impurities were also detected in the stability study of docetaxel formulation. Out of these degradation impurities two substances have been previously identified while the other three previously unreported.     

Characterization and quantitative determination of impurities in piperaquine phosphate by HPLC and LC/MS/MS

Four impurities in piperaquine phosphate bulk drug substance were detected by a newly developed gradient reverse phase high performance liquid chromatographic (HPLC) method. These impurities were identified by LC/MS/MS. The structures of impurities were confirmed by spectroscopic studies (NMR and IR) conducted using synthesized authentic compounds. The synthesized reference samples of the impurity compounds were used for the quantitative HPLC determination. The system suitability of HPLC analysis established the validity of the separation. The method was validated according to ICH guidelines with respect to specificity, precision, accuracy and linearity. Forced degradation studies were also performed for piperaquine phosphate bulk drug samples to demonstrate the stability indicating power of the newly developed HPLC method.     

氯沙坦合成工艺改造

以2-正丁基-4-氯-1H咪唑-5-甲酰基和对溴苄溴为原料,合成氯沙坦。其间经过烷基化,得到重要中间体2-正丁基-4-氯-1-[4-溴-苯甲基]-1H咪唑-5-甲酰基,再经取代的硼酸偶联、脱保护、硼氢化钠还原得到氯沙坦。此合成路线较为简便。     

树舌多糖的分离纯化、理化性质及抗炎镇痛活性研究

目的：分离纯化树舌多糖,获得均一多糖,并对其理化性质进行研究。对树舌多糖抗炎镇痛活性进行研究。方法：分离纯化采用DEAE离子交换色谱法和葡聚糖凝胶色谱法;纯度鉴定及分子量测定采用高效液相色谱法,示差折光检测器;单糖组成采用气相色谱质谱联用法测定。抗炎实验采用小鼠二甲苯性耳廓水肿法及大鼠角叉菜胶足肿胀法,镇痛实验采用小鼠醋酸扭体法。结果：获得三种均一多糖（GapsⅠ、GapsⅡ、GapsⅢ）,峰位分子量分别为6221、5535、3518D。红外光谱证实GapsⅢ结构中有β构型异头碳,核磁共振氢谱和碳谱均证实GapsⅢ结构中有α、β构型异头碳。树舌多糖明显减轻二甲苯所致的小鼠耳廓肿胀和角叉菜致大鼠足肿胀,并减少小鼠扭体次数。结论：三种多糖分子量分布及单糖组成均不同,均主要由葡萄糖组成。     

Simultaneous characterization and quantitation of 11 coumarins in Radix Angelicae Dahuricae by high performance liquid chromatography with electrospray tandem mass spectrometry

A high performance liquid chromatography with electrospray tandem mass spectrometry (HPLC–ESI-MS/MS) method has been developed to characterize and quantify 11 coumarin compounds in Radix Angelicae Dahuricae simultaneously. By using this HPLC–ESI-MS/MS method, all 11 coumarins were separated and determined within 10 min. These coumarins were detected by ESI⁺ ionization method and quantified by multiple reaction monitor (MRM). The linear regressions were acquired with r² > 0.995, respectively. The precision was evaluated by intra- and inter-day tests, and relative standard deviation (R.S.D.) values were reported within the range of 1.14–4.42% and 0.37–4.00%. The recovery studies for the quantified compounds were observed over the range of 92.1–105.6% with R.S.D. values less than 4.55%. It demonstrated that the method developed was successfully applied for identification and quantification of 11 coumarins in Radix Angelicae Dahuricae. The results showed that the contents of coumarins in Radix Angelicae Dahuricae were processed differently and varied significantly.     

医疗器械生物材料表征和化学性能检测的重要性

医疗器械生物学评价国际标准ISO10993第18和19部分作为医疗器械和生物材料生物学评价的重要组成部分越来越受到重视,在安全性评价中的重要一环就是材料的表征和材料中可萃取和迁移成分的鉴定。本文讨论那些试验可以满足这些要求。     

包裹多柔比星微球骨水泥的制备及其表征

背景：不同材料的骨水泥其性能不同,治疗的效果也会有所不同。 目的：对比观察CPC、CPC/D、CPC/M/D 3种材料的性能,探讨包裹多柔比星微球骨水泥的制备方法。 方法：采用复乳溶剂挥发法制备多柔比星微球,将多柔比星药物微球与CPC粉末以3∶7的比例均匀混合,制备成柱状包裹药物微球骨水泥。实验分为3组：①CPC组材料中只有骨水泥,不含药物和药物微球。②CPC/D组含有多柔比星药物的骨水泥。③CPC/M/D组包裹有多柔比星药物微球的骨水泥。用扫描电镜在不同放大倍数下观察样本结构特征,测量微球的粒径。采用X射线衍射分析仪测试样品的化学成分。分别对3组骨水泥在25 ℃和37 ℃下凝结时间进行测定,并计算可注射性和孔隙率。将试件置于万能生物力学试验机上进行最大抗压强度的测定,记录标本样条的最大抗压强度和断裂强度。 结果与结论: PLGA微球(100~150 µm)表面光整圆滑,骨水泥与药物混合后的微结构变化不大,无法判断药物在骨水泥中的位置和特征性表现。载微球骨水泥(100~150 µm)的结构疏散,均匀分布于CPC粉末之间。3种样品的XRD谱线与标准的羟基磷灰石的XRD谱线一致,其主峰位于XRD谱线32°附近。加入药物和微球并没有新的相产生。3种骨水泥刚投入生理盐水中材料均无崩解,但24 h后包裹微球的骨水泥表面有明显溃散,材料不完整。CPC/M/D组凝结时间最长,CPC组凝结时间最短;37 ℃时,凝结时间较长;终凝时间较长,在CPC/M/D组可达45 min左右。加入药物微球的CPC/M/D组可注射性能最好。CPC/M/D组的孔隙率最大,CPC组最小。CPC中加入药物微球后,其孔隙率可显著增加达61.67%。CPC组屈服应力最大,CPC/M/D组最小。当多柔比星原药和药物微球加入磷酸钙骨水泥后,其强度会有所降低,但两者之间差异并不显著。结果证实包裹多柔比星微球骨水泥的制备方法可靠,产物具有理想的结构和良好的性能。 关键词：磷酸钙骨水泥;微球;多柔比星;制备;表征;生物活性骨水泥材料 doi:10.3969/j.issn.1673-8225.2010.08.014     

院内制剂肝利泰片质量定性的研究

目的：肝利泰片具有清热解毒,凉血化瘀,能降低肝脏转氨酶的功效,十分适合我院专科使用。为发挥特色医院制剂,对肝利泰片的制备方法进行改进,制剂质量标准重新进行修订。方法：按照中医君臣佐使理论,合理组方,结合现代制药技术制备肝利泰片,建立性状、鉴别、检查等质量标准。结果：肝利泰片各项质量标准符合药典项下有关规定,鉴别试验重现性好,操作简便、易行。结论：新修订的制剂制备方法可行,质量稳定,质量标准符合药典规范。