[Tc]Tc-美罗芬宁和[Tc]Tc-依替芬宁在临床环境下的放化纯测定的优化质控方法。

Optimised quality control method for determination of the radiochemical purity of [Tc]Tc-mebrofenin and [Tc]Tc-etifenin in a clinical context.

机构信息

Department of Nuclear Medicine, UNICAEN, Caen, France

Department of Pharmacy, UNICAEN, Caen, France.

出版信息

Eur J Hosp Pharm. 2024 Jun 21;31(4):376-380. doi: 10.1136/ejhpharm-2022-003512.

DOI:10.1136/ejhpharm-2022-003512

PMID:36690417

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11265548/

Abstract

OBJECTIVES

In the context of a supply disruption of mebrofenin (Cholediam)-based kits for radiolabelling with technetium-99m [Tc], the medicine agencies allowed the importation of a back-up radiopharmaceutical diagnostic agent, etifenin (Techida), to ensure continuous management of patients with hepatobiliary disorders in nuclear medicine departments. There are still issues regarding the measurement of radiochemical purity (RCP) with these kits based on the European Pharmacopoeia and the Summary of Product Characteristics (SPC). This study aims to identify and to optimise, in a clinical context, the most suitable thin layer chromatography (TLC) method for the determination of the RCP in terms of speed of response and reliability for [Tc]Tc-mebrofenin and [Tc]Tc-etifenin.

METHODS

[Tc]Tc-etifenin (n=4) and [Tc]Tc-mebrofenin (n=5) were individually controlled using six different TLC methods and one high-performance liquid chromatography (HPLC) method for impurity identification (Tc and Na[Tc]TcO), RCP (%) and duration of analysis (min). Two TLC methods were selected according to the recommendations of the Pharmacopoeia and SPC, two others were exactly the same but with a heating step, and the other two corresponded to a mix between the methods of the SPC and the Pharmacopoeia that were chosen to optimise RCP determination parameters.

RESULTS

Radio-HPLC analysis allowed effective separation of [Tc]Tc-etifenin and [Tc]Tc-mebrofenin with a retention time of 8.05±0.02 min and 8.94±0.07 min, respectively, from Na[Tc]TcO (retention time 2.76±0.03 min). HPLC showed an absence of Na[Tc]TcO for [Tc]Tc-mebrofenin and 0.2% for [Tc]Tc-etifenin. Among the TLC methods, we identified the most suitable method which ensures the most compliant RCP (98.3±0.9%) in a time of 31.5±1.1 min. Also, it allowed a time saving of 15 min compared with the methods proposed by the Pharmacopoeia and the SPCs.

CONCLUSION

We propose a TLC method that accelerates quality control by an average of 15 min while guaranteeing a reliable RCP.

摘要

目的

在美罗芬宁（Cholediam）用于锝-99m [Tc]放射性标记试剂盒供应中断的情况下，药品监管机构允许进口备用放射性诊断药物乙替芬（Techida），以确保核医学部门的肝胆疾病患者得到持续治疗。这些试剂盒基于欧洲药典和产品特性摘要（SPC）的放射化学纯度（RCP）测量仍存在一些问题。本研究旨在确定并优化一种最适合的薄层色谱（TLC）方法，以确定 [Tc]Tc-美罗芬宁和 [Tc]Tc-乙替芬的 RCP，该方法在响应速度和可靠性方面具有优势。

方法

分别使用六种不同的 TLC 方法和一种高效液相色谱（HPLC）方法对 [Tc]Tc-乙替芬（n=4）和 [Tc]Tc-美罗芬宁（n=5）进行控制，用于杂质鉴定（[Tc]（TcO）和 Na[Tc]TcO）、RCP（%）和分析时间（min）。根据药典和 SPC 的建议选择了两种 TLC 方法，另外两种方法完全相同，但增加了加热步骤，另外两种方法则是 SPC 和药典方法的混合，旨在优化 RCP 测定参数。

结果

放射性 HPLC 分析可有效分离 [Tc]Tc-乙替芬和 [Tc]Tc-美罗芬宁，保留时间分别为 8.05±0.02 分钟和 8.94±0.07 分钟，而 Na[Tc]TcO 的保留时间为 2.76±0.03 分钟。HPLC 显示 [Tc]Tc-美罗芬宁中不存在 Na[Tc]TcO，而 [Tc]Tc-乙替芬中存在 0.2%的 Na[Tc]TcO。在 TLC 方法中，我们确定了最适合的方法，该方法可确保最符合要求的 RCP（98.3±0.9%），用时 31.5±1.1 分钟。此外，与药典和 SPC 提出的方法相比，该方法还节省了 15 分钟的时间。