Chaib Sarah, Hallouard François, Chennell Philip, Darcissac Caroline, Morelec Isabelle, Rioufol Catherine, Sautou Valérie, Fraysse Marc
Hospices Civils de Lyon, Centre Hospitalier de Lyon Sud, Service de Pharmacie, unité de radiopharmacie, Pierre-Bénite.
Université Clermont Auvergne, CHU Clermont-Ferrand, CNRS, SIGMA Clermont-Ferrand, ICCF, UFR Pharmacie, Clermont-Ferrand.
Nucl Med Commun. 2020 Jan;41(1):11-17. doi: 10.1097/MNM.0000000000001108.
Drug quality in medical devices is not evaluated during the marketing authorization of radiopharmaceuticals. Therefore, the extemporaneous change of packaging made for preparation of patient unit doses in a syringe is the responsibility of radiopharmacists. The present study aimed to determine the impact of packaging and storage in a polypropylene syringe on the quality of hydrophilic drugs [Tc]Tc-EDDA/HYNIC-TOC (Tektrotyd) and [Ga]Ga-DOTA-TOC (Somakit-TOC).
Appearance, pH, radiochemical purity, sterility, and endotoxin tests were performed according the current European Pharmacopoeia. Subvisible and visible particles tests of the European Pharmacopoeia were adapted due to limited preparation volume (<25 ml). Sorption tests were performed according to the literature.
After 2 h storage in a syringe, drug sorption of Tektrotyd and Somakit-TOC was of less than 2.5% and similar to other Tc-radiopharmaceuticals (range: from 1.1 ± 0.5% to 4.2 ± 0.6%). For Tektrotyd, this sorption phenomenon was positively influenced by the drug concentration and a short contact with the medical device (4.8 ± 0.2% up to 5 s vs. 2.3 ± 0.2%, n = 4; P < 0.001). For Somakit-TOC, the duration of contact with syringe had no impact (1.6 ± 0.2% up to 5 s vs. 1.7 ± 0.6%; P = 1.000). No drug radiolysis or alteration of microbiological aspects were observed. No impurity from a 3-piece-syringe was observed according to drug aspect, pH, and subvisible and visible particles, which remained within specification of the current European Pharmacopoeia.
This study found that drug sorption to packaging was compatible with clinical use and absence of drug alteration of Tektrotyd and Somakit-TOC after repackaging in a syringe in polypropylene and prolonged storage during 2 h.
放射性药物上市许可过程中未对医疗器械中的药品质量进行评估。因此，为制备注射器中患者单位剂量制剂而临时更换包装是放射药剂师的职责。本研究旨在确定聚丙烯注射器包装和储存对亲水性药物[锝]锝-乙二胺二乙酸/羟基异腈-总氧化氮（特克罗替德）和[镓]镓-多胺基多羧酸-总氧化氮（索马基特-总氧化氮）质量的影响。
根据现行欧洲药典进行外观、pH值、放射化学纯度、无菌和内毒素检测。由于制剂体积有限（<25毫升），对欧洲药典的亚可见和可见颗粒检测方法进行了调整。吸附试验根据文献进行。
在注射器中储存2小时后，特克罗替德和索马基特-总氧化氮的药物吸附率小于2.5%，与其他锝放射性药物相似（范围：从1.1±0.5%到4.2±0.6%）。对于特克罗替德，这种吸附现象受到药物浓度和与医疗器械短时间接触的正向影响（5秒内为4.8±0.2%，而2.3±0.2%，n = 4；P < 0.001）。对于索马基特-总氧化氮，与注射器接触的持续时间没有影响（5秒内为1.6±0.2%，而1.7±0.6%；P = 1.000）。未观察到药物辐射分解或微生物方面的改变。根据药物外观、pH值、亚可见和可见颗粒，未观察到三件式注射器产生的杂质，这些杂质仍在现行欧洲药典的规定范围内。
本研究发现，药物对包装的吸附与临床使用相容，且在聚丙烯注射器中重新包装并延长储存2小时后，特克罗替德和索马基特-总氧化氮没有药物改变。
