[13N]Ammonia is a cyclotron produced myocardial perfusion imaging agent. With the development of high-yielding [13N]ammonia cyclotron targets using a solution of 5 mM ethanol in water, there was a need to develop and validate an automated purification and formulation system for [13N]ammonia to be in a physiological compatible formulation of 0.9% sodium chloride since there is no widely available commercial system at this time. Due to its short half-life of 10 min, FDA and USP regulations allow [13N]ammonia to be tested in quality control (QC) sub-batches with limited quality control testing performed on the sub-batches for patient use. The current EP and the original USP method for the determination of the radiochemical purity and identity of [13N]ammonia depended on an HPLC method using a conductivity detector and a solvent free of other salts. This HPLC method created issues in a modern cGMP high volume PET manufacturing facility where the HPLC is used with salt containing mobile phase buffers for quality control analysis of other PET radiopharmaceuticals. Flushing of the HPLC system of residual salt buffers which may interfere with the [13N]ammonia assay can take several hours of instrument time. Since there are no mass limits on [13N]ammonia, a simplified TLC assay to determine radiochemical identity and purity could be developed to simplify and streamline QC. We have developed and validated a streamlined automated synthesis for [13N]ammonia which provides the drug product in 8 mL of 0.9% sodium chloride for injection. A novel radio-TLC method was developed and validated to demonstrate feasibility to quantitate [13N]ammonia and separate it from all known radiochemical impurities. The process for automated synthesis of [13N]ammonia simplifies and automates the purification and formulation of [13N]ammonia in a cGMP compliant manner needed for high-throughput manufacture of [13N]ammonia. The novel radio-TLC method has simplified [13N]ammonia quality control (QC) and now enables it to be tested using the same QC equipment as [18F]fludeoxyglucose (FDA/USP recognized name for 2-[18F]fluoro-2-deoxy-D-glucose). Both the streamlined automated synthesis of [13N]ammonia and the novel radio-TLC method have been accepted and approved by the US Food and Drug Administration (FDA) for the cGMP manufacture of [13N]ammonia.

中文翻译：

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[13N]氨的改进纯化和简化质量控制的开发、验证和监管验收。

[13N]氨是一种回旋加速器产生的心肌灌注显像剂。随着使用 5 mM 乙醇水溶液的高产[13N]氨回旋加速器靶标的开发，需要开发和验证[13N]氨的自动纯化和配制系统，以使其成为生理相容的制剂0.9% 氯化钠，因为目前还没有广泛可用的商业系统。由于其半衰期较短，为 10 分钟，FDA 和 USP 法规允许在质量控制 (QC) 子批次中对 [13N] 氨进行测试，并对供患者使用的子批次进行有限的质量控制测试。当前的 EP 和最初的 USP 测定[13N]氨放射化学纯度和特性的方法依赖于使用电导检测器和不含其他盐的溶剂的 HPLC 方法。这种 HPLC 方法在现代 cGMP 大容量 PET 制造设施中产生了问题，其中 HPLC 与含盐流动相缓冲液一起使用，用于其他 PET 放射性药物的质量控制分析。冲洗 HPLC 系统中可能干扰 [13N] 氨测定的残留盐缓冲液可能需要几个小时的仪器时间。由于 [13N] 氨没有质量限制，因此可以开发一种简化的 TLC 测定法来确定放射化学特性和纯度，以简化和简化 QC。我们开发并验证了一种简化的[13N]氨自动合成方法，可提供 8 mL 0.9% 氯化钠注射用药品。开发并验证了一种新颖的放射性 TLC 方法，以证明定量 [13N] 氨并将其与所有已知的放射化学杂质分离的可行性。[13N]氨的自动合成工艺以高通量制造[13N]氨所需的cGMP兼容方式简化并自动化了[13N]氨的纯化和配制。新型放射性 TLC 方法简化了 [13N] 氨质量控制 (QC)，现在可以使用与 [18F]氟脱氧葡萄糖（FDA/USP 认可的 2-[18F]氟-2- 名称）相同的 QC 设备进行测试。脱氧-D-葡萄糖）。[13N]氨的简化自动化合成和新颖的放射性TLC方法均已被美国食品和药物管理局（FDA）接受并批准用于[13N]氨的cGMP生产。