Chromatographic determination of chemical components of

摘要：该项目的目标是开发和验证生物产品化学成分的方法学，这些化学成分的浓度对产品的稳定性、有效性或安全性至关重要。这些包括：1)苯酚作为抗菌防腐剂用于多种用途的肠外制剂，如过敏原提取物和细菌疫苗，2)甘油用于过敏提取物作为防腐剂和/或稳定剂，3)2-苯氧乙醇作为防腐剂用于脊髓灰质炎灭活疫苗和联合细菌疫苗，4)甲醛作为流感病毒疫苗、乙肝疫苗和其他产品的灭活剂，5)人血清白蛋白和葡聚糖体积膨胀剂中的氯，6)阳性皮肤试验对照中的组胺，7)过敏原斑贴试验的有机、天然产品和复杂的合成混合物成分，8)炭疽疫苗中的苯乙二胺。 目前正在进行的工作包括以下方法开发项目： 1)将现有的基于USP《抗菌剂含量》的CBER气相色谱方法用于苯酚和2-苯氧基乙醇，这些方法使用填充柱，适用于大口径毛细管柱。大口径毛细管柱的优点包括通过更高的色谱效率获得更好的分析和增强的专属性。许多致敏提取物样品中存在的甘油吸附到固定相以及由此产生的“鬼峰”和层析容量因子的变化引起的潜在问题正在得到解决。 2)在CBER的甘油高效液相分析程序中，当应用于食品的过敏性提取物时，正在调查与电位滴定和气相色谱相比，用高效液相色谱法观察到的较低的分析结果。对不同技术的分析回收进行了比较，并对程序进行了修改，以提高回收率。 3)建立了炭疽疫苗中抗微生物防腐剂苯乙氯铵的高效液相色谱检测方法。在过去的一年里，已经开发了一种高效液相色谱方法，并进行了部分验证。已经起草了一份手稿。

Summary: The objectives of this project are to develop and validate methodologies for chemical components of biological products whose concentration is vital to product stability, efficacy or safety. These include: 1) phenol used as an antimicrobial preservative in multi-use parenterals such as allergenic extracts and bacterial vaccines, 2) glycerin used in allergenic extracts as a preservative and/or stabilizer, 3) 2-phenoxyethanol used as a preservative in inactivated poliovirus vaccine and combined bacterial vaccines, 4) formaldehyde used as an inactivating agent in influenza virus vaccine, hepatitis B vaccine and other products, 5) chloride in human serum albumin and dextran volume expanders, 6) histamine in positive skin test control, 7) organic, natural product and complex synthetic mixture components of allergen patch tests, 8) benzethonium chloride in anthrax vaccine. Current work in progress includes the following methods development projects: 1) The adaptation of existing CBER gas chromatographic methods based on USP "Antimicrobial Agents - Content" for phenol and 2-phenoxyethanol that utilize packed columns to wide-bore capillary columns. Advantages of wide-bore capillary columns include greater analytical and enchanced specificity through higher chromatographic efficiency. A potential problem arising from the adsorption of glycerin present in many allergenic extract samples to the stationary phase and resulting "ghost" peaks and changes in chromatographic capacity factors is being addressed. 2) In the CBER's HPLC procedure for glycerin, lower analytical results observed with HPLC relative to potentiometric titration and gas chromatography when applied to allergenic extracts of foods are being investigated. Analytical recoveries by the different techniques are being compared along with procedural modifications to enhance recovery. 3) The development of an HPLC procedure for the anti-microbial preservative benzethonium chloride in anthrax vaccine. In the last year, an HPLC method has been developed and partially validated. A manuscript has been drafted.