顶空—气相色谱法测定盐酸洛美利嗪中乙腈残留量

目的：建立盐酸洛美利嗪原料药中乙腈残留量的测定方法。方法：采用顶空进样法，80％DMF水溶液为溶剂，平衡温度70℃，平衡时间40min，气相色谱条件：采用不锈钢填充色谱柱：柱长2m，内径3mm，粒径为0.25-0.32mm的二乙烯苯与乙基乙烯苯共聚物有机担体为填料，柱温130℃，FID检测器，检测器温度250℃，氮气为载气，流速50mL.min^-1。结果：乙腈在23．46－234．6μg.mL^-1的浓度范围内呈良好的线性关系（r=0.9978)，回收率为96．7％（RSD＝3．8％），检出限小于40μg.g^-1。结论：本方法简单，快捷且灵敏度高，可以用于盐酸洛洛美利嗪中乙腈残留量的控制。     

In situ proteomic analysis by MALDI imaging identifies ubiquitin and thymosin-β4 as markers of malignant intraductal pancreatic mucinous neoplasms

PurposeIntraductal pancreatic mucinous neoplasms (IPMN) are precancerous cystic lesions. The aim was to investigate the in situ IPMN proteome using MALDI (Matrix-Assisted Laser Desorption/Ionisation) imaging and to characterize biomarkers associated with the grade of dysplasia.Experimental designFrozen human Branch duct -IPMN sections were selected according to dysplasia and proteomic analyses were performed by MALDI imaging to obtain mass spectra distribution. The most discriminating peaks were identified using tissue extraction and nanoLC-ESI-MS/MS. Identified peaks were validated in independent series of IPMN by immunochemistry on surgical specimens (tissue-microarrays (TMA), n = 45) and endoscopic ultrasound fine-needle aspiration (EUS FNA) samples (n = 25).ResultsBD-IPMN samples with low (n = 10) and high (n = 10) grades of dysplasia were analyzed. Differential spectra of proteins were found in the two groups with significantly different intensities (n = 15). The two peaks (intense in high grade IPMN) (m/z 8565 and 4747) were characterized as the monomeric ubiquitin (Mascot score = 319.22) and an acetylated fragment of thymosin-β4 (2–42) (Omssa score = 1.37 E−9). Validation on TMA and EUS FNA samples confirmed that ubiquitin was overexpressed in high grade dysplasia (p = 0.04 and p = 0.0004). Thymosin-β4 expression was confirmed on TMA by immunohistochemistry on high grade IPMN (p = 0.011).ConclusionUbiquitin and thymosin-β4 are overexpressed in IPMN with high grade dysplasia. Positive immunochemical staining on EUS-FNA material is a major argument in support of preventive resection.     

The Selection of a Pharmaceutical Salt—The Effect of the Acidity of the Counterion on Its Solubility and Potential Biopharmaceutical Performance

A roadmap for the selection of a pharmaceutical salt form for a development candidate is presented. The free base of the candidate did not have sufficient chemical stability for development. The initially selected salt form turned out to be undevelopable because it was unstable during scale-up synthesis and storage. The rationale for the new solid form screening and the criteria for selection are discussed. Before the final selection, the pH solubility profiles of the 2 new salts, a benzoate and a besylate, were compared. Atypical solubility behavior was observed for the benzoate salt in hydrochloric acid with and without normal saline. A scheme is proposed illustrating how the pKas of the counterion and active pharmaceutical ingredient, the medium composition, and final pH affect the solubility and solution equilibria of the 2 selected salt forms. This scheme also includes the equilibria between solution and solid phases in different pH ranges. The pharmaceutical importance of this research is that it sheds light on how the acidity of the counterion can affect the solubility of the selected salt form in the gastric environment. With a well-designed formulation strategy, this property potentially can be translated to optimal biopharmaceutical performance of the drug product.     

Direct Measurement of ATP7B Peptides Is Highly Effective in the Diagnosis of Wilson Disease

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Solving the 'Brown snake paradox': in vitro characterisation of Australasian snake presynaptic neurotoxin activity

Pseudonaja textilis (Eastern Brown snake) and Oxyuranus scutellatus scutellatus (Coastal taipan) are clinically important Australian elapid snakes, whose potent venoms contain the presynaptic (β) neurotoxins, textilotoxin and taipoxin, respectively, and a number of postsynaptic neurotoxins. However, while taipan envenoming frequently results in neurotoxicity, Brown snake envenoming causes an isolated coagulopathy and neurotoxicity is rare. This phenomenon is called the 'Brown snake paradox'. This study compared the pharmacology of both venoms and their respective presynaptic neurotoxins to investigate this phenomenon. From size-exclusion high performance liquid chromatography (HPLC) analysis textilotoxin represents a significantly smaller proportion (5.7%) of P. textilis venom compared to taipoxin in O. s. scutellatus venom (20.4%). In the chick biventer cervicis nerve-muscle (CBCNM) preparation both venoms caused concentration-dependent neurotoxicity, with P. textilis venom being significantly more potent than O. s. scutellatus venom. Conversely, taipoxin was significantly more potent than textilotoxin when compared at the same concentration. Textilotoxin only partially contributed to the overall neurotoxicity of P. textilis venom, while taipoxin accounted for the majority of the neurotoxicity of O. s. scutellatus venom in the CBCNM preparation. Compared with taipoxin, textilotoxin is less potent and constitutes a smaller proportion of the venom. This is likely to be the reason for the absence of neurotoxicity in envenomed humans thus explaining the 'Brown snake paradox'.     

GC法测定正电子类放射性药物制剂中有机溶剂残留量

目的建立GC法测定正电子类放射性药物注射剂中有机溶剂残留量。方法色谱柱为DB-FFAP石英毛细管柱（30 m×0.32 mm,0.5μm）,FID检测器,载气为氮气。进样口温度200℃;检测器温度250℃;程序升温：初始温度40℃,保持5 min,以40℃·min-1升温至200℃,保持5 min。手动进样,不分流模式。结果乙腈在0.008%~0.080%（g·g-1）范围内线性关系良好（r=0.9981）,[18F]AV-133和[18F]AV-45制剂的平均加样回收率分别为94.26%和93.74%,RSD为3.27%和5.23%（n=9）;二甲亚砜在0.10%~1.00%（g·g-1）范围内线性关系良好（r=0.9964）,[18F]AV-133和[18F]AV-45制剂的平均加样回收率分别为96.10%和100.75%,RSD为5.17%和6.52%（n=9）。结论该法简单、灵敏、准确,重复性好,适用于[18F]AV-133和[18F]AV-45制剂有机溶剂残留量的检测。     

毛细管气相色谱法同时测定工作场所空气中丙烯腈和乙腈

目的建立优化工作场所空气中丙烯腈和乙腈的毛细管气相色谱法。方法使用DB-FFAP 30m×0.25 mm×0.25 m毛细管柱和氢火焰离子化检测器,同时测定工作场所空气中乙腈和丙烯腈。结果检出限丙烯腈2.0μg/mL,相关系数为0.999 5;乙腈3.0μg/mL,相关系数为0.999 7;解吸效率为85.10%～92.60%,相对标准偏差为3.20%～4.10%。结论该方法灵敏、快速、准确。     

顶空毛细管气相色谱法测定盐酸莫西沙星中残留溶剂的含量

目的：建立盐酸莫西沙星中醋酸、乙酸乙酯、甲醇、乙醇、乙腈5种残留溶剂含量的测定方法。方法：顶空毛细管气相色谱法,氢火焰离子化检测器,醋酸以二甲基亚砜为溶剂,色谱柱为DB-FFAP（0．25mm×30m,0．25μm）;乙酸乙酯、甲醇、乙醇、乙腈以水为溶剂,异丙醇为内标,色谱柱为HP-INNOWax（0．32mm×30m,0．5μm）。结果：5种残留溶剂在对应于限度的20％～200％浓度范围内有良好的线性关系,平均回收率为97．3％～108．4％。结论：所建方法简单,准确,重现性好,可用于盐酸莫西沙星残留溶剂的含量控制。