Centre for Diagnostic Nuclear Imaging, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
Department of Pharmacy Practice, Faculty of Pharmacy, Universiti Teknologi MARA, 42300 Bandar Puncak Alam, Selangor, Malaysia.
Curr Radiopharm. 2021;14(2):131-144. doi: 10.2174/1874471013999201027215704.
Organic solvents play an indispensable role in most of the radiopharmaceutical production stages. It is almost impossible to remove them entirely in the final formulation of the product.
In this presented work, an analytical method by gas chromatography coupled with flame ionization detection (GC-FID) has been developed to determine organic solvents in radiopharmaceutical samples. The effect of injection holding time, temperature variation in the injection port, and the column temperature on the analysis time and resolution (R ≥ 1.5) of ethanol and acetonitrile was studied extensively.
The experimental conditions were optimized with the aid of further statistical analysis; thence, the proposed method was validated following the International Council for Harmonisation (ICH) Q2 (R1) guideline.
The proposed analytical method surpassed the acceptance criteria including the linearity > 0.990 (correlation coefficient of R), precision < 2%, LOD, and LOQ, accuracy > 90% for all solvents. The separation between ethanol and acetonitrile was acceptable with a resolution R > 1.5. Further statistical analysis of Oneway ANOVA revealed that the increment in injection holding time and variation of temperature at the injection port did not significantly affect the analysis time. Nevertheless, the variation in injection port temperature substantially influenced the resolution of ethanol and acetonitrile peaks (p < 0.05).
The proposed analytical method has been successfully implemented to determine the organic solvent in the [F]fluoro-ethyl-tyrosine ([F]FET), [F]fluoromisonidazole ([F]FMISO), and [F]fluorothymidine ([F]FLT).
有机溶剂在大多数放射性药物生产阶段都起着不可或缺的作用。在产品的最终配方中，几乎不可能完全去除它们。
在本研究工作中，开发了一种气相色谱法结合火焰离子化检测（GC-FID）的分析方法，用于测定放射性药物样品中的有机溶剂。广泛研究了进样保持时间、进样口温度变化和柱温对乙醇和乙腈分析时间和分辨率（R≥1.5）的影响。
借助进一步的统计分析优化了实验条件；然后，根据国际协调委员会（ICH）Q2（R1）指南对所提出的方法进行了验证。
所提出的分析方法超过了验收标准，包括线性度>0.990（R 相关系数）、精密度<2%、LOD 和 LOQ、所有溶剂的准确度>90%。乙醇和乙腈之间的分离具有可接受的分辨率 R>1.5。Oneway ANOVA 的进一步统计分析表明，进样保持时间的增加和进样口温度的变化并不显著影响分析时间。然而，进样口温度的变化会显著影响乙醇和乙腈峰的分辨率（p<0.05）。
该分析方法已成功用于测定[F]氟乙基酪氨酸（[F]FET）、[F]氟米索硝唑（[F]FMISO）和[F]氟脱氧胸苷（[F]FLT）中的有机溶剂。
