A new two-strip TLC method for the quality control of technetium-99m mercaptoacetyl-triglycine (99mTc-MAG3)

Marietta Straub,Michel Leresche,Fabien Devynck,Claude Pilloud,Rolf Hesselmann,Nicolas Stritt

doi:10.1186/s41181-018-0040-5

Abstract

Background99mTc-mercaptoacetyl-triglycine (99mTc-MAG3) has been used for dynamic renal imaging since about 30 years. Free pertechnetate (99mTcO4), colloidal 99mTc ((99mTcO2)n), 99mTc-tartrate (precursor), precomplexes (99mTc-(MAG3)x) and lipophilic 99mTc-MAG2 are the main radiochemical impurities that may occur in the preparation. The total amount of these impurities has to be identified before release of the product for patient administration to guarantee patient safety and good image quality. The European Pharmacopoeia suggests a method based on high-pressure liquid chromatography analysis in combination with a paper chromatography. This analytical method is time consuming, expensive and requires specially trained technicians. As a consequence, it is not widely applied in nuclear medicine radiopharmacies.ResultsWe developed a simple method for radiochemical purity testing of 99mTc-MAG3. The method is based on thin layer chromatography with two strips to be developed in parallel. Method validation was carried out in comparison to the official methods of the companies and to the European Pharmacopoeia method. It was tested on specificity, accuracy, robustness and precision.ConclusionThe proposed method is able to identify and quantify the sum of all impurities occurring in the preparation, respecting the acceptance criteria for the radiochemical purity defined by the official methods. Hydrophilic and lipophilic compounds are identified separately and results are obtained within less than 20 minutes. Our method is simple, cost effective, fast and is suitable for employing dose calibrators or radiometric scanners.

Highlights

In the early 80’s, 99mTc-MAG3 was introduced as a new dynamic renal imaging agent (e.g. (Fritzberg et al, 1986; Taylor et al, 1987; Taylor et al, 1987; Brandau et al, 1988; Bormann et al, 1995))
New TCL method The new two-strip Thin layer chromatography (TLC) method for the routine quality control (QC) of Mallinckrodt Pharmaceutical 99mTc-MAG3 labeling we developed is based on a first separation on an iTLC-SG chromatography paper with a 60:40 % mixture of ethyl acetate and methyl ethyl ketone (MEK), already mentioned in the literature (Chen et al, 1993), combined with a new solvent for the second separation on the same type of support, with a 90:10 % ethanol/ water mixture
Solid-phase extraction (SPE) Method of the company As already revealed by other studies (Chen et al, 1993; Murray et al, 2000; Vinberg, 2000; Ponto, 2005; Millar & Hesslewood, 2004), the SPE method for RPC testing suggested by the company

Summary

Introduction

In the early 80’s, 99mTc-MAG3 was introduced as a new dynamic renal imaging agent (e.g. (Fritzberg et al, 1986; Taylor et al, 1987; Taylor et al, 1987; Brandau et al, 1988; Bormann et al, 1995)). In the early 80’s, 99mTc-MAG3 was introduced as a new dynamic renal imaging agent For the preparation of 99mTc-MAG3 commercial sterile kits are available in form of a lyophilized pharmaceutical product. (van Hemert et al., 2005; Nosco et al, 1993; Seetharaman et al, 2006; Chen et al, 1993; Package insert for Technescan MAG3. Mallinckrodt Suisse SA, 2003; Package insert for ROTOP-MAG-3. Kit. Heider AG, 2006; Package insert for Technescan MAG3. Specific biodistribution of 99mTc-MAG3 is crucial for the patient safety and image quality and the radiochemical purity (RCP) of the radiopharmaceutical has to be guaranteed (Fritzberg et al, 1986; Brandau et al, 1988). A liable quality control (QC) method quantifying the radiochemical impurities occurring in the radiopharmaceutical preparation is indispensable to release the product for patient administration

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