布洛芬原料药中残留有机溶剂和微量金属杂质的检测研究

目的:针对布洛芬的生产工艺,建立原料药中残留有机溶剂(二氯甲烷、乙醇)和微量金属杂质(铝、钴、镍)的检测方法。方法:残留溶剂采用顶空毛细管气相色谱法,使用DB-624毛细管色谱柱(30 m×0.53 mm,膜厚3.0μm),载气为氮气,检测器采用FID,柱温采用程序升温,顶空平衡温度80℃,平衡时间60 min,以N,N-二甲基甲酰胺(DMF)为溶剂;金属杂质采用微波消解-石墨炉原子吸收法测定,通过石墨炉程序升温进行测定。结果:在残留溶剂的测定中,两待测组分之间的分离度为6.3,在测定浓度范围内r分别为0.9999和0.9998,检测限分别为0.2μg.g-1和2μg.g-1,加样回收率分别为101.1%和101.0%。在3种金属杂质的测定中,检测限分别为5 ng.g-1、5 ng.g-1和10 ng.g-1;在测定浓度范围内,r分别为0.9996,0.9993,0.9998;3种待测元素的加样回收率均大于90.0%;结论:测定方法准确可靠,灵敏度高,适用于布洛芬原料药中残留溶剂和微量金属杂质的分析检测。     

梯度洗脱HPLC法测定盐酸克林霉素棕榈酸酯及制剂的有关物质

目的:建立梯度洗脱HPLC法测定盐酸克林霉素棕榈酸酯原料药、分散片、颗粒及干混悬剂的有关物质。方法:采用Agilent ZORBAX XDB-C8(4.6 mm×150 mm,5μm)柱,流动相A为5 mmol·L-1醋酸铵溶液-乙腈(50∶50),流动相B为乙腈,流速为1.0 mL·min-1,线性梯度洗脱,检测波长为230 nm。结果:盐酸克林霉素棕榈酸酯与10种中间体、副产物完全分离。重复性RSD为2.9%,检测限为10μg·mL-1。结论:方法简便、灵敏、重复性好,可用于本品的质量控制。     

制备型高效液相色谱法在药物杂质研究中的应用

制备型高效液相色谱法是一种使用高压、大流量液体输送系统在高分辨率、大内径、高载量分离柱上进行样品高纯度分离的液相色谱制备方法。应用该方法分离的产品在纯度、回收率、分离效率等方面远远优于传统的制备方法,因此在药物研究、生产领域得到广泛应用。介绍制备型高效液相色谱法的研究概况,特点,影响制备型高效液相色谱分离纯化的因素,以及在药物杂质研究中的实际应用,并对制备型高效液相色谱技术存在的问题与发展方向进行总结。     

Measurements and Characteristics of Nitrogen-Containing Compounds in Atmospheric Particulate Matter in Beijing, China

The total nitrogen (TN) and water-soluble nitrogenous ions were determined by using CHN Elemental Analyzer and ion chromatography method, respectively, from November 24, 1998 to February 12, 1999 in Beijing. The average concentrations of TN, NH₄ ⁺ and NO₃ ⁻ were 10.62 μg N m⁻³, 6.67 μg m⁻³ and 10.01 μg m⁻³, respectively. The total inorganic nitrogen (IN) calculated from NH₄ ⁺ and NO₃ ⁻ was 7.45 μg N m⁻³, accounting for 70% of TN, i.e., 30% of TN existed as organic nitrogen form (ON). The correlation between ON and other pollution tracers showed that, coal combustion, biomass burning, soil humic matter and secondary formation were the important sources of ON in particulate matter in Beijing.     

ICP-MS法测定注射用头孢美唑钠中31种元素杂质的含量

摘 要 目的：建立电感耦合等离子体质谱（ICP-MS）法,测定注射用头孢美唑钠中的31种具有潜在风险的元素杂质：砷（As）、镉（Cd）、汞（Hg）、铅（Pb）、钴（Co）、镍（Ni）、钒（V）、金（Au）、铱（Ir）、锇（Os）、钯（Pd）、铂（Pt）、铑（Rh）、钌（Ru）、银（Ag）、硒（Se）、铊（Tl）、钡（Ba）、钼（Mo）、铬（Cr）、铜（Cu）、锂（Li）、锑（Sb）、锡（Sn）、硼（B）、铝（Al）、硅（Si）、钛（Ti）、锰（Mn）、铁（Fe）,锌（Zn）的含量。方法：采用Agilent 8900 ICP-MS Triple Quad电感耦合等离子体质谱仪,运用碰撞模式消除双电荷干扰,以高基体样品进样系统模式进样,通过在线内标方式消除基质效应,样品稀释直接进样测定。结果：该方法能同时测定31种元素杂质含量,其线性关系良好（r ＞ 0.99）、重复性试验的RSD小于20%（n = 6）、回收率在70%～140%（n = 9）,均满足USP 43 < 233 > 方法学验证碰撞模式的要求。应用该方法测定了20批来自不同生产企业的国产制剂及1批原研制剂中上述元素的含量。结论：国产及原研制剂中元素杂质含量均低于限度的30%,风险可控;所建立的方法操作简便,准确灵敏,专属性强,重复性好,可为化学药品中元素杂质控制方法提供参考。本试验对国评样品的元素杂质迁移情况开展筛查,不仅能够掌握注射用头孢美唑钠质量整体水平,并且可以为监管部门对上市后药品再评价提供技术储备和数据支持。     

Synthetic origin of illicit methylamphetamine in Australia: 2011–2020

The National Measurement Institute's Methylamphetamine Profiling Program has evolved over the last 15 years to address analytical challenges faced with changes in illicit methylamphetamine production. The program involves organic and inorganic analysis of methylamphetamine to determine the precursors and synthetic route used in manufacture. This paper discusses changes in the methylamphetamine chemical profile for samples received at this laboratory during January 2011 to December 2020. In particular, changes observed in the methylamphetamine purity, potency, synthetic route, precursor and precursor synthetic origin are discussed. Over 13,180 samples were analysed during this period consisting of samples seized on the streets and the Australian border. This paper shows correlations between methylamphetamine seizures at the Australian border with international clandestine laboratory and precursor seizures trends. As the illicit drug landscape changes so too must our approach to chemical profiling if we are to confidently determine the synthetic origin of methylamphetamine.     

Developing an Injectable Formula Containing an Oxygen-Sensitive Drug: A Case Study of Danofloxacin Injectable

The purpose of this study was to assess the impact of impurities in formulation components, antioxidants, formulation pH, and processing/packaging on the extent of color change associated with oxidation of danofloxacin injectable. The methods used in this study include reversed-phase HPLC, UV-VIS spectrophotometry, atomic absorption spectroscopy, visual observation, and iodimetric titration for quantification of the antioxidant. The results from this study revealed that trace impurities from two different excipients significantly contributed to color change associated with oxidation. Polyvinyl pyrrolidone (PVP) introduced trace levels of peroxides into the solution. A second excipient also had a significant impact on stability because it introduced trace metal impurities into the product. The minimization of oxygen levels alone in the solution and headspace was not sufficient to completely eliminate the product instability. The addition of an antioxidant, monothioglycerol (MTG), resulted in a formulation less sensitive to processing variables. The impact of pH on the performance of MTG was also studied. At pH 7.5, MTG resulted in significant improvement in stability; however, at pH 6.0 it was not effective as an antioxidant. Process modifications alone may not be sufficient to prevent oxidation. Chemical approaches, such as pH control, addition of an antioxidant, and control of components should be considered first as means of enhancing stability of oxygen-sensitive solutions.     

Seasonal Changes in Whole-Cell Metal Levels in Protozoa of Activated Sludge

In this study the authors quantify, and correlate, whole-cell elemental levels of vorticellids in activated sludge, over a 1-year period, andAspidisca cicadaandOpercularia coarctataon one sampling date. The aim was to determine the extent, and seasonal variation, of metal uptake and/or accumulation, to give new information regarding the fate and dynamics of the cellular elements, and to determine how they are related to each other over time and between species, in an environment exposed to high levels of heavy metals. Samples of activated sludge were collected monthly, and whole-cell elemental levels of vorticellids determined by scanning electron microscopy electron probe X-ray microanalysis (XRMA). Positive intersample correlations were found between phosphorus and three elements, sulfur, potassium, and iron. Potassium and calcium levels correlated positively with sulfur levels. Iron levels were positively correlated with potassium levels. Levels inA. cicadasampled from activated sludge were also compared with the same species grownin vitro,previously isolated from the same sewage treatment works. The level of cellular elements varies considerably with time, and between species from the same environment. Vorticellids could tolerate varying levels of aluminum, copper, iron, and zinc. Decreased iron levels were associated with decreased phosphorus and potassium levels.     

Survey of Chlorinated Hydrocarbons and Other Organic Volatile Impurities in Captopril Raw Materials and Tablets

Pharmaceutical Research -