N-亚硝胺类基因毒性杂质的研究进展

自“缬沙坦事件”之后，N-亚硝胺类基因毒性杂质引起了业界的广泛关注。本文概述了药物中N-亚硝胺类基因毒性杂质和相关检测方法的研究进展，以及近20年来国内外有关药物中基因毒性杂质监管指南的完善历程。N-亚硝胺类基因毒性杂质作为一类高反应活性的基因毒性杂质，主要来源于药物合成过程中发生的副反应，以及药物在储存或者运输过程中发生的氧化或还原等反应。所有的动物实验表明，N-亚硝胺类具有很强的致癌性。在理论上，所有药物都存在N-亚硝胺类杂质或被N-亚硝胺类杂质污染的风险，由于该类化合物在药物中常以痕量形式存在，在分析检测过程中药物基质干扰大，因此建立便捷、高效的分析方法是非常有必要的。     

顶空气相色谱-质谱法测定布南色林原料药中遗传毒性杂质

目的：建立顶空气相色谱-质谱法测定布南色林原料药中甲磺酸甲酯、甲磺酸乙酯和甲磺酸异丙酯3种遗传毒性杂质含量的方法。方法：采用顶空气相色谱-质谱法，以甲磺酸丁酯为内标，按内标标准曲线法进行甲磺酸甲酯、甲磺酸乙酯和甲磺酸异丙酯的含量测定。色谱条件：DB-WAX毛细管色谱柱（30 m×0.25 mm×0.25 μm）；程序升温，初始柱温为40℃，维持3 min，升温速率为30℃·min^-1，终止温度150℃，保持2 min；进样口温度为110℃；载气（He）流速为0.6 mL·min^-1；进样量为1 mL；进样方式为分流进样，分流比为20：1。质谱条件：电子轰击离子源（EI），扫描方式为选择性离子检测；离子源温度为200℃；接口温度为150℃；电子能量为70 eV；溶剂延迟1 min。结果：3种杂质成分之间的分离度均大于2.0；甲磺酸甲酯、甲磺酸乙酯、甲磺酸异丙酯检测质量浓度线性范围均为0.025~3.0 μg·mL^-1（r ≥ 0.998 5）；精密度、稳定性、重复性试验的RSD<5%；加样回收率分别为93.40%~101.40%（RSD为3.2%，n=9）、92.80%~99.70%（RSD为2.5%，n=9）和96.30%~100.75%（RSD为1.6%，n=9）。结论：该方法简便、准确、灵敏、迅速，可用于布南色林原料药中3种遗传毒性杂质的测定。     

原发灶未明的颈结转移癌31例临床分析

本文对我院自1983年至1989年收治的原发灶未明的颈结转癌31例进行临床分析。男18例。女13例;平均年龄47.5岁,颈结位于颈单侧26例,双侧5例;位于颈上部18例次、颈中部6例次、颈下部8例次、锁骨上窝4例次(右3、左1)。在转移癌位于颈上、中部的18例中,8例作咽轴部放射治疗,其3和5年生存率明显优于不作咽轴照射者,包括放疗在内和综合治疗比不加放疗的结果好。有4例疗后追踪找到了原发灶,其中2例为腮腺癌,2例分别为肺鳞、腺癌。转移灶位于锁骨上窝的4例预后最差。     

A reversed-phase high-performance liquid chromatographic assay for the determination of N-acetylcysteine in aqueous formulations

A stability-indicating assay is described for the determination of N-acetylcysteine in aqueous pharmaceutical formulations. The sample is diluted to an appropriate concentration with dilute aqueous orthophosphoric acid. An aliquot of the solution, containing added l-tyrosine as an internal standard, is chromatographed using a 10-mum C(18) stationary phase with dilute orthophosphoric acid (pH 2.0) containing 0.5% w/v of sodium perchlorate as the mobile phase. The assay, which has a relative standard deviation of about 0.8%, can also be used as a test for related impurities in N-acetylcysteine. It is also suitable for determining the N-acetylcysteine content of the drug substance.     

小儿不明原因长期发热的临床诊断

目的：探讨小儿不明原因长期发热的病因及诊断方法。方法：回顾性总结分析符合FUO诊断标准的患儿76例。结果：76例中能明确诊断的72例,确诊率94．8％,未明确诊断4例（5．2％）。确诊病例中,感染性疾病42例（59％）,结缔组织病12例（16．7％）,肿瘤性疾病10例（13．8％）,其它4例（5．4％）。结论：临床只要做到详尽而确切的病史采集和必要的实验室检查,多数FUO是能明确诊断的;感染性痢疾、结 缔组织性及肿瘤性疾病是FUO的主要病因。     

口服葡萄糖酸钙提质生产注射葡萄糖酸钙的探讨

目的：生产注射葡萄糖酸钙。方法：以口服葡萄酸钙为原料，通过提高其澄明度和降低其杂质含量使其达到注射葡萄糖酸钙的质量要求。结论：本工艺方法具有投入设备少、副反应少、产品质量好等特点。     

Analyse histologique et moléculaire des métastases cérébrales

The first step in the diagnosis of a metastatic brain lesion is to exclude a primary central nervous sytem tumour, followed by verification or identification of the primary tumor site, in order to guide the clinician to specific therapy. In addition to morphological features, ancillary immunohistochemical study is most effective for the evaluation of a metastatic neoplasm of unknown primary. Although the main principles are same, there are slight variations in the approach to the secondary lesion in the central nervous system versus other regions. Indeed, immunohistochemical approach focuses on the most common tumor types associated with secondary brain colonization: lung cancer, breast cancer and melanoma. Several studies have reported that targeted therapies are capable of reducing brain metastases in melanoma or non-small cell lung cancer, sometimes with a high dramatic response. These results have clearly impacted routine neuropathological practice. It is likely that molecular subtyping of central nervous system metastases will play an increasing role in the future. In accordance with the recommendations of Inca (French national cancer institute), the pathologist develops appropriate strategies for molecular and immunohistochemical analysis, in order to provide results as soon as possible. This article summarizes the diagnosic approach to brain metastases, with a focus on the recent emergence of targeted therapies.