Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, 98 Nagyerdei St., H-4032 Debrecen, Hungary.
Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, 98 Nagyerdei St., H-4032 Debrecen, Hungary.
J Pharm Biomed Anal. 2022 Jan 5;207:114425. doi: 10.1016/j.jpba.2021.114425. Epub 2021 Oct 9.
A novel gas chromatography (GC) method for quantitation of volatile organic compounds (VOCs) in F- and C-radiopharmaceuticals listed in the European Pharmacopoeia (Ph. Eur.) was proposed. Optimized chromatographic parameters were used for separation of ethanol, acetone, acetonitrile, tetrahydrofuran (THF), dibromomethane (DBM), 2-dimethylaminoethanol (deanol), N,N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) which could be detected in radioactive drug samples. The calculated peak resolutions (R) were higher than 2.0 at ethanol concentration of up to 11 m/m%. Reproducible results could be obtained using base deactivated fused silica wool as packing material of inlet liner. Validation parameters showed excellent linearity (r ≥0.9998) in the range from 10 to at least 120% of concentration limit of solvents. The accuracy was determined as recovery of concentrations which ranged from 99.3% to 103.8%. Additionally, the relative standard deviation (RSD) of each solvent for inter-day and intra-day precision were in the range of 0.5-4.2% and 0.4-4.4%, respectively. The limit of quantitation (LOQ) for ethanol, acetone, acetonitrile, THF, DBM, deanol, DMF and DMSO was 0.48, 0.42, 0.43, 0.46, 4.35, 0.73, 0.68 and 0.50 mg/L, respectively. The developed procedure was successively applied for quantitation of ethanol, acetone, acetonitrile and deanol in radioactive drug samples of [C]methionine, [C]choline, 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) and O-(2-[F]fluoroethyl)-L-tyrosine ([F]FET). The proposed GC method applying flame ionization detection (FID) could be adapted in routine quality control of most frequently used positron emission tomography (PET) radiopharmaceuticals to perform the determination of residual solvents with analysis time of 12 min.
提出了一种用于定量测定欧洲药典（Ph. Eur.）中列出的 F 型和 C 型放射性药物中挥发性有机化合物（VOCs）的新型气相色谱（GC）方法。优化的色谱参数用于分离乙醇、丙酮、乙腈、四氢呋喃（THF）、二溴甲烷（DBM）、2-二甲氨基乙醇（deanol）、N，N-二甲基甲酰胺（DMF）和二甲基亚砜（DMSO），这些物质可以在放射性药物样品中检测到。在乙醇浓度高达 11 m/m%的情况下，计算出的峰分辨率（R）高于 2.0。使用经过碱处理的熔融石英毛作为进样衬管的填充材料，可以获得重现性好的结果。验证参数表明，在溶剂浓度至少为 120%的 10-范围内具有极好的线性（r≥0.9998）。准确度通过测定浓度范围在 99.3%至 103.8%之间的回收率来确定。此外，各溶剂的日内和日间精密度的相对标准偏差（RSD）分别在 0.5-4.2%和 0.4-4.4%范围内。乙醇、丙酮、乙腈、THF、DBM、deanol、DMF 和 DMSO 的定量限（LOQ）分别为 0.48、0.42、0.43、0.46、4.35、0.73、0.68 和 0.50mg/L。该方法成功地应用于放射性药物样品中[C]蛋氨酸、[C]胆碱、2-脱氧-2-[F]氟-D-葡萄糖（[F]FDG）和 O-（2-[F]氟乙基）-L-酪氨酸（[F]FET）中乙醇、丙酮、乙腈和 deanol 的定量测定。该方法采用火焰离子化检测（FID），可应用于最常用的正电子发射断层扫描（PET）放射性药物的常规质量控制，分析时间为 12 分钟，用于测定残留溶剂。
