Closset Mélanie, Colsoul Maire-Lise, Bihin Benoît, Hecq Jean-Daniel, Odou Pascal, Galanti Laurence
Medical Laboratory, CHU UCL NAMUR, Yvoir, Belgium.
Drug Stability Research Group, CHU UCL NAMUR, Yvoir, Belgium.
J Pharm Technol. 2024 Dec;40(6):296-299. doi: 10.1177/87551225241285319. Epub 2024 Oct 7.
Closed system transfer devices (CSTD) help to reduce the exposure of healthcare professionals to hazardous drugs. They may be used in stability studies conducted on anticancer drugs. During a stability study about polyolefin bags of gemcitabine, Tevadaptor® device was suspected of causing a bias in the evaluation of the concentrations of the first aliquots extracted from the bags.
The objectives are to determine whether the use of a CSTD to prepare a drug solution and to withdraw it from a bag can interfere on the measured concentration compared to the expected one and to suggest hypothesis to explain the phenomenon.
In the first experiment, three polyolefin bags of gemcitabine (5.4 mg/mL) were prepared under aseptic conditions using the Tevadaptor Luer Lock Adaptor®. The day of preparation, five aliquots of 3.8 ml each were sequentially withdrawn from each polyolefin bag using the same device. After one day, a new aliquot was withdrawn from each bag. In the second experiment, three polyolefin bags of gemcitabine (5.4 mg/ml) were prepared under aseptic conditions using a needle. One aliquot was extracted using a needle after the preparation from each bag, and another aliquot was extracted after one day. The concentrations of all aliquots were measured by liquid chromatography coupled to a photodiode array detector during the same run.
The concentrations of the first aliquots extracted on day zero from the polyolefin bags using the Tevadaptor Luer Lock Adaptor® exhibit an overestimation of 26% ([95%CI: 23%-29%] P<0.001) compared to the others. Overestimation is not found for subsequent aliquots, or while using a needle to bypass the Tevadaptor® device.
This case highlights the bias that may arise when using CSTDs in stability studies. They should be used with comprehensive understanding of their technical specifications.
密闭式系统转移装置（CSTD）有助于减少医护人员接触危险药物。它们可用于抗癌药物的稳定性研究。在一项关于吉西他滨聚烯烃袋的稳定性研究中，Tevadaptor®装置被怀疑在评估从袋子中提取的首批等分试样浓度时产生偏差。
目的是确定与预期浓度相比，使用CSTD制备药物溶液并从袋子中取出药物溶液是否会干扰测量浓度，并提出假设来解释该现象。
在第一个实验中，使用Tevadaptor Luer Lock Adaptor®在无菌条件下制备三个吉西他滨聚烯烃袋（5.4mg/mL）。制备当天，使用同一装置从每个聚烯烃袋中依次取出五个3.8ml的等分试样。一天后，从每个袋子中取出一个新的等分试样。在第二个实验中，使用针头在无菌条件下制备三个吉西他滨聚烯烃袋（5.4mg/ml）。制备后，使用针头从每个袋子中提取一个等分试样，一天后再提取另一个等分试样。在同一次运行中，通过液相色谱-光电二极管阵列检测器测量所有等分试样的浓度。
与其他试样相比，使用Tevadaptor Luer Lock Adaptor®在第零天从聚烯烃袋中提取的首批等分试样浓度高估了26%（[95%CI：23%-29%]P<0.001）。后续等分试样未发现高估现象，或者在使用针头绕过Tevadaptor®装置时也未发现高估现象。
本案例突出了在稳定性研究中使用CSTD时可能出现的偏差。应在全面了解其技术规格的情况下使用它们。
